SlideShare una empresa de Scribd logo

Materi Workshop Diabetes Melitus untuk Dokter Umum - Practical Management of Diabetes and Its Complication for General Practitioner

•
•
Dayu Agung Dewi Sawitri
Dayu Agung Dewi Sawitri

Materi Workshop Diabetes Melitus untuk Dokter Umum - Practical Management of Diabetes and Its Complication for General Practitioner. Diselenggarakan oleh Perkeni, Kementerian Kesehatan RI dan STENO Diabetes Center

Salud y medicina
1 de 130
Descargar para leer sin conexión
2 Sponsored by PT. Novo Nordisk Indonesia New INSPIRE by PERKENI and STENO Diabetes Center A National Diabetes Management Course
3 Overall Training Objectives ü  To provide participants with a holistic understanding of diabetes management – from diagnosis to late-stage complications ü  To provide participants with practical tools, guidelines, demonstrations and take-home educational materials to improve and optimize their diabetes treatment ü  To emphasize and demonstrate the importance of early treatment of diabetes to avoid long-term complications About INSPIRE Training in Indonesia ¥  Curriculum, workshops and cases designed in collaboration between PB. PERKENI and STENO Diabetes Center ¥  Joint PERKENI – STENO certificates will be distributed for a participation rate of 80% Curriculum Sponsorship ¥  The INSPIRE Training courses, the development of the curriculum and all support programs are sponsored by PT. Novo Nordisk Indonesia to support and enhance the quality of diabetes training across Indonesia Coordination Coordination and Alignment
4 Why INSPIRE? BE INSPIRED AS A DOCTOR… …TO INSPIRE YOUR PATIENTS A TRULY UNIQUE PLACE ¥  An independent research and patient care institution funded by the capital Region of Copenhagen and Novo Nordisk ¥  Patient care, research and education – focusing exclusively on diabetes care and prevention ¥  One of the leading diabetes research and health promotion centers in the world ¥  Treating 6.200 patients with Type 1 and Type 2 Diabetes through the ‘team-based’ method
5 STENO EDUCATION CENTER Facts: ¥  Collaborating with Novo Nordisk and the Capital Region on education of HCPs ¥  Frontiers Steno Symposium ¥  STAR courses in India/Middle East/China ¥  Educational tools ¥  Partnerships with endocrine society's in selected countries (China / Indonesia) Rules of the INSPIRE Program ¥  Certificates can only be given for minimum 80% attendance ¥  Limit Mobile Phone Activity to the Coffee Breaks ¥  Be back on time after lunch- and coffee breaks RULES
6 Why do we see a massive increase in people with Type 2 Diabetes across the World? Cockram CS 2000. HKMJ; 6 (1): 43-52 Mohan et al 2007. Indian J Med Res; 125: 217-230 Adapted from IDF Diabetes Atlas 4th ed., 2009 Aging population Dietary changes Reduced physical activity UrbanisationUnhealthy lifestyle choices
7 Diabetes is developing much faster than anticipated in Indonesia… RISKESDAS Survey 2007 Diagnosed people with Diabetes Undiagnosed people with Diabetes Total people with diabetes Total people with IGT** 1.5% 4.2% 5.7% 10.2% * Source: RISKESDAS Survey 2007 – 24.417 subjects , >15 years ol from 33 provinces ** IFT = Impaired Glucose Tolerance Approximately 10 million people with diabetes in Indonesia …and our diabetes patients are not in good glycemic control DiabCare Indonesia 2008 illustrated the need for more intensive treatment to decrease FPG and PPG n: 1.823 patients with diabetes 208 144 100 140 0 20 40 60 80 100 120 140 160 180 200 220 mg/dl PPG (mg/dl)FPG (mg/dl) GlycemicControlLevel PERKENI GuidelinesDiabCare 2008 Source: Novo Nordisk Data on File
8 Pre-Test & Questionnaire X X Time: 30 minutes Please fill out the Evaluation Scheme after Day 1 and Day 2 In your participant folder
9 Early Detection and Standardized Diabetes Management Lecture: 30 minutes Early Detection and Standardized Diabetes Management Lecture Main Learning Points ¥  Understand the process from screening to diagnosis and the associated national guidelines ¥  Understand the importance of treating diabetes and intensify treatment on diabetes via blood glucose- and HbA1c monitoring ¥  Understand the reason and need for routine follow-up and reaching individual targets to avoid complications
10 Some Definitions before we start… Common Definitions Abbreviation Definition NGT Normal Glucose Tolerance (Gula Darah Normal) FPG Fasting Plasma Glucose (Gula Darah Puasa) PPG Post-Prandial Plasma Glucose (Gula Darah Post Prandial) IGT Impaired Glucose Tolerance (Toleransi Glukosa Terganggu) IFG Impaired Fasting Glucose (Gula Darah Puasa Terganggu) HbA1c Average amount of glucose in the bloodstreams over a 3-month period Classification of Diabetes ¥  Type 1 diabetes ¥  Absolute insulin deficiency due to the destruction of pancreatic beta-cells ¥  Type 2 diabetes ¥  Type 2 is characterized by insulin resistance with relative insulin deficiency to a predominately secretary defect with insulin resistance ¥  Other specific types ¥  Gestational diabetes ¥  Glucose intolerance first detected in pregnancy that often resolves after the birth of the baby Diabetes Care 1997; 20: 1183-1197
11 Difference between Type 1 and Type 2 Diabetes Comparison of Type 1 and Type 2 Diabetes Features Type 1 Diabetes Type 2 Diabetes Onset Sudden Gradual Age at Onset Any age (mostly young) Mostly in adults Body Habitus Thin or normal Often obese Ketoacidosis Common Rare Autoantibodies Usually present Absent Endogenous Insulin Low or absent Normal, decreased or increased Prevalence Less prevalent More prevalent, typically 90-95% of all people with diabetes Type 2 diabetes is a progressive disease Lebovitz. Diabetes Reviews 1999;7:139–53 (data are from the UKPDS population: UKPDS 16. Diabetes 1995;44:1249–58) HOMA: homeostasis model assessment
12
13 Classical Diabetes Symptoms Polyuria Unexplained weight loss Polydipsia Polyphagia ¥  Excessive Urination at night ¥  Excessive Hunger ¥  Excessive Thirst ¥  Weight Loss even if food in-take is normal Other Diabetes Symptoms Blurred Vision Numbness and/or Tingling Fatigue Itchy Skin Impotence ¥  Damaging blood vessels in the eyes ¥  Numbness and tingling in hands, legs and feet ¥  Frequent fatigue regardless of exercise ¥  Affects legs, feet, and hands ¥  Physical and Physiological
14 4 Simple Steps from Screening to Diagnosis Conduct 1st Blood Test 2 Conduct 2nd Blood Test (if required) and establish Diagnosis 3 Screen patients with diabetes risk factors 1 Inform Patient and Initiate treatment 4 Step 1: Risk Factors – PERKENI screening risk factor guideline Unmodifiable Risk Modifiable Risk Diabetes Associated Risk ¥  Race and Ethnic ¥  Family History of Diabetes ¥  History of Gestational Diabetes ¥  History of delivery a baby more than 4.000g ¥  History of low birth weight <2.500g ¥  Overweight (BMI >23) ¥  Hypertension > 140/90 mmHg ¥  Dyslipidemia (HDL < 35 mg/dl and/or triglycerides >250 mg/dl ¥  Unhealthy Diet ¥  Limited Physical Activity ¥  Polycystic Ovary Syndrome (PCOS) or another clinical condition related to insulin resistance ¥  Metabolic Syndrome (IGT, IFG, History of Coronary Artery Disease , stroke and/or PAD) Source: KONSENSUS: Pengelolaan Dan Pencegahan DM Type 2
15
16 Step 4: Inform Patient and Initiate Treatment Diabetes Mellitus IGT IFG ¥  Evaluation of Nutritional Status ¥  Evaluation of Diabetes Complications ¥  Evaluation of Required Food Regulation ¥  Decision on medicines ¥  Education ¥  Food Regulation ¥  Physical Exercise ¥  Ideal Body Weight ¥  OADs are unnecessary at this stage Source: KONSENSUS: Pengelolaan Dan Pencegahan DM Type 2 Cut-points: Diabetes, IGT and IFG mg/dL 2-hour Plasma Glucose (PPG) FastingPlasmaGlucose(FPG) mg/dL 140 200 100 126 NGT (Normal Glucose Tolerance) Diabetes IFG (Impaired Fasting Glucose IGT (Impaired Glucose Tolerance) Diabetes
17 Diagnosis of Type 2 Diabetes KONSENSUS: Pengelolaan Dan Pencegahan DM Type 2 1.  Classical symptoms of Diabetes (+) & Random plasma glucose concentration ≥ 200 mg/dl 2.  Classical symptoms of Diabetes (+) & Fasting Plasma Glucose ≥ 126 mg/dl. 3.  2-hour post-OGTT ≥ 200 mg/dl. Note: ¥  Classical symptom of diabetes (+), only need 1 abnormal BG ¥  No classical symptom of diabetes, need 2 x abnormal BG level in a different days Or Or
18 What is good glycemic control? ¥  Overall aim to achieve glucose levels as close to normal as possible ¥  Minimise development and progression of microvascular and macrovascular complications FPG <130 mg/dL HbA1c < 7.0% PPG <180 mg/dL FPG <110 mg/dl HbA1c < 6.5% PPG <145 mg/dL IDF2 ADA1 PERKENI3 1. American Diabetes Association Diabetes Care 2009;32 (Suppl 1):S1-S97 2. IDF Clinical Guidelines Task Force. International Diabetes Federation 2005. 3. PERKENI 2011 Konsensus . FPG <100 mg/dl HbA1c < 7% PPG <140 mg/dl HbA1c correlation with blood glucose level David M. Nathan, Judith Kuenen, Rikke Borg, Hui Zheng, David Schoenfeld, and Robert J. Heine, for the A1c-Derived Average Glucose (ADAG) Study Group. Diabetes Care 2008 The relationship between A1C and eAG is described by the formula 28.7 X A1C – 46.7 = eAG
19 Risk of Complications increases as Hb1Ac increases and that’s why diabetes must be treated Stratton IM et al. BMJ 2000;321:405–12 0 20 40 60 80 5 6 7 8 9 10 11 Myocardial infarction Microvascular disease Adjusted for age, sex, and ethnic group. The relationship between A1C and mg/dl is described by the formula 28.7 X A1C – 46.7 = mg/dl. Incidenceper1.000patient- years 12697 154 183 212 240 269 Mean HbA1c (%) Mean mg/dl The benefits of good blood glucose control are clear Good control is ≤ 7.0% HbA1c HbA1c measures the average blood glucose level over the last three months Source: UKPDS = United Kingdom Prospective Diabetes Study. Stratton IM et al. BMJ. 2000;321(7258):405-412. Deaths related to diabetes Microvascular complications Myocardial infarction -14% -37% -21% HbA1c -1%
20 Practical Monitoring Scheme Source: Konsensus Pengelolaan dan Pencegahan DMT2 di Indonesia. PERKENI. 2011. Diabetes Care 2012. Penatalaksanaan Diabetes Melitus Terpadu. 2009 Practical Monitoring Scheme Cont… Source: Konsensus Pengelolaan dan Pencegahan DMT2 di Indonesia. PERKENI. 2011. Diabetes Care 2012. Penatalaksanaan Diabetes Melitus Terpadu. 2009
21 Individualized Treatment based on several criteria to control blood glucose Early Detection and Standardized Diabetes Management Lecture Main Learning Points ¥  Understand the importance of treating diabetes and reaching individual targets to avoid complications ¥  Understand the process from screening to diagnosis and the associated national guidelines ¥  Understand the reason and need for routine follow-up and intensify treatment on diabetes via blood glucose- and HbA1c monitoring Summary ¥  Diabetes is a progressive disease that must be treated in order to avoid long-term complications ¥  Good glycemic control according to PERKENI is: ¥  HbA1c <7% ¥  FPG: <100 mg/dl ¥  PPG: <140 mg/dl ¥  Patient treatment need to be individualized according to the characteristics of each particular patients
22 Handout: Overview of Diabetes National Clinical Practice Guidelines Ref: Rudianto et al. The Indonesian Society of Endocrinology’s Summary Article of Diabetes Mellitus National Clinical Practice Guidelines. JAFES Vol. 26 (1), May 2011
23 Diabetes and its Co-morbidities – Hypertension and Dyslipidemia Lecture: 30 minutes Diabetes HypertensionDyslipidemia Diabetes and its Co-morbidities – Hypertension and Dyslipidemia Lecture Main Learning Points • Understand the relationship between diabetes and hypertension • Understand how hypertension should be treated and how diabetic patients with hypertension should be treated • Understand the relationship between diabetes and dyslipidemia • Understand how dyslipidemia should be treated and how diabetic patients with dyslipidemia should be treated
24 Diabetes and its Co-morbidities Hypertension Categories for Blood Pressure Levels in Adults (JNC VII)* * Aged 18 years or older Blood Pressure Level (mmHg) Category Systolic Diastolic Normal < 120 And < 80 Prehypertension 120 -139 Or 80 – 89 High Blood Pressure Stage 1 Hypertension 140 - 159 Or 90 - 99 Stage 2 Hypertension > 160 Or > 100 When systolic and diastolic blood pressures fall into different categories, the higher category should be used to classify blood pressure level. For example, 160/80 mmHg would be stage 2 hypertension (high blood pressure) Why focus on the triangle of diabetes, hypertension and dyslipidemia? Diabetes HypertensionDyslipidemia “Triangular Focus’ Treatment Implications • 40-60% of type 2 diabetes patients will also have either hypertension, dyslipidemia or both • Hypertension and Dyslipidemia are both well established risk factors for diabetes-related complications like CVD and nephropathy • Early and correct treatment of hypertension and dyslipidemia can delay the onset of diabetes complications
25 Diabetes Is a Major Multiplier of Cardiovascular Risk in Patients With Hypertension Systolic Blood Pressure and Cardiovascular Mortality Stamler J, et al. Diabetes Care. 1993;16:434–444. 130 85 62 42 2218 245 153 160 112 73 55 0 50 100 150 200 250 CardiovascularMortality RatePer10,000Person-Years 120 - 139<120 >200 Systolic Blood Pressure mmHg 160 -179 180 - 199140 -159 Diabetes No Diabetes Effect of Blood Pressure Control in the UKPDS Tight vs. Less Tight Control Any diabetes-related endpoint Diabetes-related deaths Heart failure Stroke Myocardial infarction Micro vascular disease Tight Control  1,148 Type 2 patients  Average BP lowered to 144/82 mmHg (controls: 154/87); 9-year follow-up 24 32 56 44 21 37 Risk Reduction (%) P value 0.0046 0.019 0.0043 0.013 NS 0.0092 UKPDS Group. BMJ. 1998;317:703-713.
26 UKPDS hypertension sub-study: Tight blood pressure control reduces complications in diabetes UKPDS Group. BMJ. 1998;317:703-713. Stroke Years 0 20 15 10 5 44% risk reduction P = 0.013 30 5 7 86421 9 Patientswithevents(%) Years Diabetes-related deaths 0 40 30 20 10 30 5 7 86421 9 32% risk reduction P < 0.02 Patientswithevents(%) Less tight control: mean BP 154/87 mmHg Tight control with captopril or atenolol: mean BP 144/82 mmHg Years Microvascular disease Patientswithevents(%) 0 20 15 10 5 30 5 7 86421 9 37% risk reduction P < 0.01 Major Outcomes of the Hypertension Optimal Treatment (HOT) Trial Diabetes Sub-group shows that lowering blood pressure is beneficial for diabetes patients with hypertension Hansson L, et al. Lancet. 1998;351: 1755-1762. 11 8 24 11 4 18 33 11 0 5 10 15 20 25 30 CV Mortality Events/1000Pt-Years MIMajor CV Events <85 mmHG (n=501) <90 mmHG (n=501) <80 mmHG (n=499) Diastolic Target
27 ADA Recommendations on Hypertension Diabetes Care 2012; 35 (Suppl. 1): p29Years Systolic Blood Pressure <130 mmHg, however depending on patient characteristics and response to therapy, higher or lower SBP targets may be appropriate GOAL SBP or DBP 130 – 139 mmHg 80 – 89 mmHg SBP or DBP > 140 mmHg > 90 mmHg • Lifestyle therapy alone for a maximum of 3 months • If targets are not achieved, start treatment with pharmacological agents • Should receive pharmacological therapy in addition to lifestyle therapy JNC 7 Algorithm for Treatment of Hypertension Lifestyle Modifications Initial Drug Choices Not at Goal BP (<140/90 mm Hg) (<130/80 mm Hg for those with diabetes or chronic kidney disease) Without Compelling Indications Stage 1 HTN (SBP 140-159 or DBP 90-99 mm Hg) Thiazide-type diuretics for most. May consider ACEI, ARB, BB, CCB, or combination. Optimize dosages or add additional drugs until goal BP is achieved. Consider consultation with hypertension specialist. Drug(s) for the compelling indications other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB) as needed. Without Compelling Indications Not at Goal BP Stage 2 HTN (SBP 160 or DBP 100 mm Hg) 2-drug combination for most (usually thiazide-type diuretic and ACEI, ARB, BB, or CCB) Chobanian AV et al. JAMA. 2003;289:2560-72
28 ADA Recommendations on Hypertension Cont. Diabetes Care 2012; 35 (Suppl. 1): p29 Lifestyle Treatment Pharmacological Treatment • Weight Control • Increased consumption of fruit, vegetables and low fat diet • Sodium restriction • Increased physical activity • Alcohol moderation • Pharmacologic therapy • A regimen that includes either an ACE I or ARB • If one class is not tolerated, the other should be substituted • Other classes but RAS are equally good. • Multiple drugs are generally required • If ACE I, ARBs, or diuretics are used: • Monitor: kidney function and s- potassium Most relevant drugs are indicated for hypertension patients with diabetes Chobanian, et al.2004
29 Dyslipidemia Dyslipidemia in Diabetes • Total cholesterol • LDL cholesterol • HDL cholesterol • Triglyceride
30 Mean Plasma Lipids at Diagnosis of Type 2 Diabetes UKPDS Number of Pts TC (mg/dl) LDL-C (mg/dl) HDL-C (mg/dl) TG (mg/dl) Type 2 Control MEN * P<0.001, ** P<0.02 comparing type 2 vs. control group 2139 213 139 39** 159* 52 205 132 43 103 Type 2 Control WOMEN 1574 224 151* 43* 159* 143 217 135 55 95 UKPDS Group. Diabetes Care 1997;20:1683-1687. Diabetes & Dyslipidemia • NHANES 1999–2000 prevalence of control of LDL-C, HDL-C, and triglycerides (TG) among those with vs. those without diabetes M.J. Jacobs et al. /Diabetes Research and Clinical Practice 70 (2005) 263–269 Control of LDL-C indicated as <2.6 mmol/l (<100 mg/dl), HDL-C >1.0 mmol/l (40 mg/dl) for men and >1.3 mmol/l (50 mg/dl) for women, and TG <1.7 mmol/l (150 mg/dl).
31 Heart Protection Study Proportions of patients with major vascular events in the Heart Protection Study (HPS) by year of follow-up evaluation and numbers of events prevented with simvastatin treatment per 1,000 individuals The American Journal of Cardiology, Volume 92, Issue 4, Supplement 2, 21 August 2003, Pages 3–9 Meta-analysis of statin treatment in diabetes Risk reduction of clinical outcomes per 40 mg/dL (1.0 mmol/L) reduction in LDL cholesterol • 21% reduction major vascular events • 25% reduction in coronary revascularisation • 21% reduction in stroke • 9% reduction in all-cause mortality • 13% reduction in CVD mortality • No difference in non-vascular mortality Independent of baseline LDL or prior CVD Lancet, 371, 117-25, 2008
32 Updated ATP III LDL-C Goals and Cutpoints for Therapy Grundy SM et al. Circulation 2004;110: 227-239 Risk Category LDL-C (mg/dL) Goal Initiation Level for TLC Consideration Level for Drug Therapy High risk: CHD or CHD risk equivalents (10-yr risk >20%) <100 (optional: <70) ≥100 ≥100 (<100: consider drug options) Moderately high risk: 2+ risk factors (10-yr risk 10–20%) <130 (optional: <100) ≥130 ≥130 (100–129: consider drug options) Moderate risk: 2+ risk factors (10-yr risk <10%) <130 ≥130 ≥160 Lower risk: 0–1 risk factor <160 ≥160 ≥190 (160–189: LDL-C– lowering drug optional) Statin therapy algorithm Third report of the National Cholesterol Education Program (NCEP) Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III): final report. National Heart, Lung, and Blood Institute and National Institutes of Health Website. http://www.nhlbi.nih.gov/guidelines/cholesterol/atp3full.pdf. Accessed November 25, 2009.
33 Conclusions on Statins ADA 2012 • Statin therapy should be considered for all individuals with type 2 diabetes • independent of baseline lipid levels if previously CVD • Statin therapy should be considered for all patients above 40 y with more than 1 risk factor • Especially if • Prior CVD • Albuminuria • Smokers • Hypertension • Severe family history • Lack of data for age < 40y • Should be considered in type 1 diabetes at high risk of CVD or with signs of diabetic complications Risk stratification as per NCEP ATP III guideline Major risk factors as per ATP III guidelines Major risk factors to modify treatment of LDL (excluding LDL cholesterol) Nonmodifiable Modifiable Age: male ≥45 years and female ≥55 years Hypertension: BP ≥140/90 mm Hg or on antihypertensive agents Family history of premature CHD: CHD in male first-degree relative <55 years and in female first- degree relative <65 years Low HDL cholesterol levels: <40 mg/dL (HDL ≥60 mg/dL is protective) Cigarette smoking
34 Fibrates algorithm Fibrates • Greater reductions in triglycerides • Increase HDL cholesterol more effective than statins • Combined treatment (fibrates + statins) decrease triglycerides and LDL cholesterol and increase HDL cholesterol more than statins or fibrates as monotherapy • However, the combination of fenofibrate and simvastatin does not reduce the rate of fatal cardiovascular events, nonfatal MI, or nonfatal stroke, as compared with simvastatin alone
35 Nicotinic Acid • Significant reduction in triglycerides and increases HDL compared to fibrates and statins • Significant effects in combination with statins on Intima Media Thickness (proxy marker of atherosclerosis) compared to statins alone • Adverse effects: vasodilatation (flushing), increases HbA1c, increase uric acid • No data on Nicotinic acid on CVD endpoints Order of Priorities for Treatment of Diabetic Dyslipidemia in Adults Adapted from American Diabetes Association. Diabetes Care 2000;23(suppl 1):S57-S60. LDL Cholesterol Lowering1 • First choice: HMG CoA reductase inhibitor (statin) • Second choice: Bile acid binding resin or fenofibrate HDL cholesterol raising2 • Behavior interventions such as weight loss, increased physical activity and smoking cessation • Glycemic control • Difficult except with nicotinic acid, which is relatively contraindicated, or fibrates. Evidence for treating HDL with drugs is limited and priority should be on lowering LDL Triglyceride lowering3 • Glycemic control first priority • Fibric acid derivative (gemfibrozil, fenofibrate) • Statins are moderately effective at high dose in hypertriglyceridemic subjects who also have high LDL cholesterol
36 Diabetes and its Co-morbidities – Hypertension and Dyslipidemia Lecture Main Learning Points • Understand the relationship between diabetes and hypertension • Understand how hypertension should be treated and how diabetic patients with hypertension should be treated • Understand the relationship between diabetes and dyslipidemia • Understand how dyslipidemia should be treated and how diabetic patients with dyslipidemia should be treated Summary • Measure blood pressure at all visits because hypertension should be treated to prevent complications of diabetes • Target 130/80 mmHg or 125/75 mmHg if proteinuria> 1 gram/24 hrs. • Control lipid profile to prevent cardiovascular event in diabetes • Target of LDL-cholesterol in diabetes: • No CVD :<100 mg/dL • Prior CVD or high risk : <70 mg/dL
37 Non-Pharmacology Intervention Lecture: 30 minutes Non-Pharmacology Intervention Lecture Main Learning Points ¥ The relationship between nutrition and blood glucose control ¥ Understand the eating pattern in the local region that could play a role on the fat or carbohydrate intake ¥ Determine healthy and unhealthy eating and initiating and assessing dietary intervention in a clinical setting ¥ Understand the importance of exercise and the relationship between exercise and blood glucose control ¥ Understand the relationship between smoking and diabetes associated complications
38 Diet & Exercise in Diabetes ¥  Important in type 1 and type 2 diabetes ¥  In type 2 diabetes: ¥  Obesity and physical inactivity are major risk factors ¥  Diet and exercise may provide good long- term glycaemic control in some patients ¥  Improved cardiovascular status ¥  Cost-effective Something went wrong… 2.5 million years 50 years
39 Medical Nutrition Therapy in Diabetes As integral part of : ¥  Prevention and management of diabetes ¥  Component of diabetes education ¥  Prevention of diabetes complication Source: Diabetes Care, Vol. 31, Suppl. 1, 2008 Targets of Medical Nutrition Therapy in prevention and management of Type 2 Diabetes Diabetes Care, Vol. 31, Suppl. 1, 2008 Individual with Diabetes Risk- factors or with pre-diabetes Individual with diagnosed Diabetes 1) To reduce the risk of diabetes and cardiovascular disease by promoting healthy food choices and physical activity leading to moderate weight loss that is maintained. 1)  To achieve and maintain: ¥  Blood Glucose levels in the normal range ¥  A lipid profile that reduces the risk for vascular diseases ¥  Blood Pressure levels in the normal range 2)  To prevent / delay progressivity of chronic complications 3)  To address individual nutrition needs, taking into account personal and cultural preferences and willingness to change
40 The relationship between healthy nutrition and blood glucose Source: Long-term Effects of a Lifestyle Intervention on Weight and Cardiovascular Risk Factors in Individuals with Type 2 Diabetes; Four Yesr Results of the Look AHEAD Trial. The Look AHEAD Reseach Group DSE: Diabetes Support and Education ILI: Intensive Lifestyle Intervention The Fundamentals of food management for diabetes patients Similar with healthy people: ¥  Balance food intake according to calories and nutrition needs for each individual ¥  Weight loss, increased physical activity, and weight management ¥  Consistency in day-to-day carbohydrate intake at meals and snacks ¥  Nutritional content ¥  Timing of meals and snacks ¥  Carbohydrates are the principal determinant for blood glucose Emphasis (‘triple Js)’: ¥  Jadwal (Schedule) ¥  Jenis (Type) ¥  Jumlah (Amount)
41 Calorie Requirement Formula ¥  Harris–Benedict formula ¥  Men = 66 + (13.7 x weight in kg) + (5 x height in cm) - (6.8 x age in years) ¥  Women = 65.5 + (9.6 x weight in kg) + (1.7 x height in cm) - (4.7 x age in years) Frankenfield DC, et al. The Harris-Benedict studies of human basal metabolism: history and limitations. J Am Diet Assoc. 1998;98:439-445 Guidelines for a healthy diet PERKENI 2011 ¥  Healthy balanced diet composed of: ¥  45-65% carbohydrate ¥  20-25% fat ¥  10–20% protein Fat Carbohydrate Protein
42 Carbohydrate Eat Less of These Eat More of These Fruit, Low fat Milk, Beans, Brown rice, Yoghurt, Whole wheat bread White sugar, Brown sugar, White bread, White rice, DASH Pyramid
43 Proteins Eat Less of These Eat More of These Chicken, Fish, TofuSausages, processed meat, Shrimps and shell fish, Red Meat Fat Eat Less of These Eat More of These Avocado, Nuts, Olives, Oils rich in poly and mono unsaturated fats Coconut, Margarine/butter, Cheese, Oils/fats rich in saturated fat
44 Understanding portion sizes is important Recommendation to take smaller portion sizes of the less recommended food Rice boiled – 100 g Calorie – 175 kcal Carbohydrates – 40gm Rice boiled – 200 g Calorie – 350 kcal Carbohydrates – 80gm Noodles boiled – 200 gm Calorie – 175 Kcal Carbohydrates – 40 gm Source: Daftar Bahan Makanan Penukar How you cook is important Less Healthy More Healthy
45 The relationship between exercise and blood glucose Diabetology & Metabolic Syndrome, 2009, 1:27 HbA1c values collected 12 weeks prior to the initiation of the exercise program (Baseline), at the start of the exercise program (Pre-Intervention) and at the completion of the 10 weeks program (Post-Intervention). Ten week changes are denoted by * (p < 0.05). A difference between exercise groups is denoted by # (p < 0.008). Both resistance and aerobic exercise were effective in reducing blood glucose levels and HbA1c levels
46 Boulé NG, et al. JAMA 2001;286:1218-27. -0.66%-0.7 -0.6 -0.5 -0.4 -0.3 -0.2 -0.1 0.0 0.1 0.2 Exercise Non-exercise control ChangeinHbA1c frombaselinetopost-intervention (weightedmeandifference) p<0.001 Effect was weight- independent 0.08% Pooled meta-analysis of 14 exercise trials % Exercise significantly reduces HbA1c Source: Boule NG et al. Effects of exercise on glycemic control and body mass in T2 Diabetes: JAMA2001; 286:1218-27
47 Diabetes and Smoking Background Before diabetes ¥  Smoking is associated with insulin resistance ¥  dose-response relationship between smoking and the risk of type 2 diabetes ¥  Stopping to smoke decreases the risk of type 2 diabetes Additional to diabetes ¥  Smoking increases the risk of developing diabetic complications - nephropathy, neuropathy and retinopathy ¥  Independent risk factor for CVD and all-cause mortality ¥  Smokers are also lipid intolerant ¥  Smoking cessation increases HDL and reduces LDL levels, despite weight gain Facchini. F. S et al Lancet, (1992) 339 (8802) , pp. 1128-1130 . Al-Delaimy WK, et al. Arch Intern Med. 2002;162(3):273-279. Patja, K., et al Journal of Internal Medicine, 258: 356–362. Chaturvedi N, Diabetes Care 1995; 18: 785–92.Jacobs DR Jr et al Arch Intern Med 1999;159: 733-40. Axelsen M., et al (1995), Journal of Internal Medicine, 237: 449–455.D.P. Mikhailidis, et al (1998) The Journal of the Royal Society for the Promotion of Health 118: 91 Significant reduction in mortality of diabetes patients among non-smokers* 591 368323275215 1,984 1,443 1,2191,249 1,012 0 500 1,000 1,500 2,000 MortalityRate(per100.000person-years) Past 1-14 cig / dayNever 15-34 cig / day 35+ cig / day Non-diabetic woman Diabetic woman Source: Wael K. Al-Delaimy et al. Diabetes Care 24: 2043-2048, 2001 cig = cigarette RR of mortality 1.31 1.43 1.64 2.19 * Adjusting BP, high cholesterol & other CV risk factors
48 Practical Initiation of Diet Programs for diabetes patients Food Mapping Systems Food Mapping System can be used for patient education to increase patient compliance with diet scheme Beras Merah Kukus Nasi Putih Nasi Goreng Ayam Bakar Ayam Goreng Ayam Goreng Tepung Ikan Bakar / Kukus Ikan Goreng Udang Goreng Sayur Kukus Kukus Dim Sum Dim Sum Goreng Group Discussion
49 Practical Initiation of Diet Programs for diabetes patients Healthy Plate Models T-shaped plate model to loose weight Y-shaped plate model to maintain weight Portion Control Plate was effective in inducing weight loss and decreased use of hypoglycemic medications in obese patients with type 2 diabetes mellitus Vegetables Carbo- hydrate / Starch Protein Carbo- hydrate / Starch Vegetables Protein Pedersen DE et al. Arch Intern Med. 2007; 167 Practical Initiation of Exercise Programs for diabetes patients CRIPE Pricnciple CRIPE: Continuous, Rhytmic, Interval, Progressive, Endurance Continuous ¥  Exercises should be done continuously without rest (e.g. 30 minutes of jogging without rest) Rhythmic ¥  Choose more rhythmical sports where regular contraction and relaxation are possible (e.g. walking, jogging, running and swimming) Interval ¥  Exercises with both quick and slower actions (e.g. running followed by jogging) Progressive ¥  Increase intensity according to abilities (heart rate target: 75-85% from maximum heart rate) Endurance ¥  Exercise for endurance to improve cardiorespiratory abilities (e.g. walking, jogging, swimming, cycling)
50 Non-Pharmacology Intervention Lecture Main Learning Points ¥  The relationship between nutrition and blood glucose control ¥  Understand the eating pattern in the local region that could play a role on the fat or carbohydrate intake ¥  Determine healthy and unhealthy eating and initiating and assessing dietary intervention in a clinical setting ¥  Understand the importance of exercise and the relationship between exercise and blood glucose control ¥  Understand the relationship between smoking and diabetes associated complications Summary ¥  It’s importance to educate the patients about diet, exercise and non-smoking recommendations as sufficient evidence is available about the improvement in HbA1c levels through lifestyle intervention ¥  Simple patient supporting tools like food mapping system or the CRIPE exercise principle are readily available ¥  It is important to negotiate with the patients on which food choices are the healthiest based upon the patient eating patterns
51 Diabetes Acute Complications – Hypoglycemia and DKA Lecture: 30 minutes Management of Hypoglycemia Lecture Main Learning Points • Understand the hypoglycemia mechanism, diagnosis and how hypoglycemia should be treated • Understand how to adjust OAD - or insulin dosage after hypoglycemic events • Understand what causes a DKA event, how DKA is treated and what to do if you experience a patient with DKA
52 Why address hypoglycemia in diabetes training • Reducing HbA1c levels associated with prevention or delay in complications and death • Hypoglycaemia is a limiting factor in achieving glycaemic targets • Hypoglycaemia is associated with morbidity and rarely even be fatal • Optimising glycaemic control is of obvious importance: • $465 billion USD spent to treat diabetes and its complications in 2011; hypoglycaemia is cost-intensive • 6.8% of global all-cause mortality attributed to diabetes in 2010 (4 million deaths) Cryer et al 2003. Diabetes Care; 26,6: 1902-1912. IDF Diabetes Atlas tth ed., 2009. Roglic and Unwin 2010. Diabetes Research and Clinical Practice; 87: 15-19 What is hypoglycemia? neurogenic symptoms due to low plasma glucose levels • Low plasma glucose levels defined as: • ≤70 mg/dL (ADA)1 • <60 mg/dl (PERKENI)2 • <72 mg/dL (CDA)3 • Symptoms respond to the administration of carbohydrate3 1. ADA. Diabetes Care 2005;28:1245–9; 2. PERKENI Konsensus 2011. 3. Yale et al. Canadian J Diabetes 26:22–35 ADA, American Diabetes Association; CDA, Canadian Diabetes Association; A state of neuroglycopenic and/or neurogenic symptoms due to low plasma glucose levels
53 Most common symptoms of Hypoglycemia Patients (%) Circumoral paraesthesia Difficulties in concentration Slurred speech Blurred vision 0 20 40 60 80 100 Hunger Palpitations Vertigo Cold feeling Anxiety Euphoria Weakness Tremor Sweating Headache Nausea Pramming 1991 Sequel of hypoglycaemia • Mild symptomatic hypoglycaemia • No direct serious clinical effects • May impair subsequent hypoglycaemia awareness • Severe hypoglycaemia associated with • Stroke and transient ischaemic attacks • Memory loss/cognitive impairment • Myocardial infarction • Injury (direct/indirect) • Death Turner et al. (UKPDS 33), 1998. The Lancet; 352: 837-853
54 Risk Factors of Hypoglycemia • General risk factors for hypoglycaemia:1,2 • delayed or missed meal • consuming a smaller meal than planned • exercise • use of diabetes medications • drug/alcohol consumption • increased insulin sensitivity or decreased insulin clearance • Risk factors for major hypoglycaemia:3,4 • age/duration of diabetes treatment • intensive glycaemic control • hypoglycaemia unawareness • sleep • antecedent hypoglycaemia • history of major hypoglycaemia 1.Briscoe & Davis. Clin Diabetes 2006;24:115–21; 2. ADA Workgroup on Hypoglycemia. Diabetes Care 2005;28:1245–9. 3. Frier. Diabetes Metab Res Rev 2008;24:87–92; 4. Cryer. Diabetes 2008;57:3169–76 Hypoglycaemic events occur more often in Type 1 diabetes patients and are less frequent and less severe in Type 2 diabetes patients both on conventional and intensive therapy Adapted from DCCT Research Group. Diabetes 1997. Adapted from Bonds D., data presented at ADA 2009 Eventsper100PatientYears HbA1c (%) Conventional Therapy 0 10 20 30 40 50 60 70 80 90 100 6.0 6.5 7.0 7.5 8.0 8.5 9.0 ACCORD (T2 DM) DCCT (T1 DM) Eventsper100PatientYears HbA1c (%) Intensive Therapy 0 10 20 30 40 50 60 70 80 90 100 6.0 6.5 7.0 7.5 8.0 8.5 9.0 DCCT (T1 DM) ACCORD (T2 DM)
55 Treatment of mild Hypoglycemia First: 10–20 g fast-acting carbohydrate, e.g.: • 3–6 glucose tablets* • 90–180 ml fizzy drink or squash (not diet)** • Two teaspoons of sugar added to a cup of cold drink • 50–100 ml energy drink (e.g. Lucozade®)* Then: • If next meal is due, add extra carbohydrate • If next meal is not due, eat longer-acting carbohydrate, such as biscuits or a sandwich Treating early signs RCN 2004 *not widely available in Indonesia ** Indonesia  processed drinks (tea, etc) Prevention of Hypoglycemic Events • Education • Symptoms • Self management • Proper food intake in therapy • For elderly patients, caregiver should also be educated • Repetitive education in patients with decreased cognitive function • Self monitoring blood glucose (SMBG) • Exercise planning • Measuring blood glucose before exercise • Consuming carbohydrate • Adjust insulin dose based on the blood glucose level • Right type and dose for therapy
56 Treatment of moderate-to-major Hypoglycemia Patient requires assistance with treatment If conscious: • Carer should help the patient to consume 10–20 g fast-acting carbohydrate • Dextrose gel* may be useful If unconscious: • Don’t put anything in patient’s mouth • IM or SC glucagon* or IV glucose should be administered • Emergency services should be called Treating late signs RCN 2004; Cryer 2010 IM: intramuscular, SC: subcutaneous, IV: intravenous Adjusting Dosage after a Hypoglycemic Event If hypoglycemic events are repeated, OAD and / or Insulin dosages should be reduced OAD: Depending on drug Insulin: Initially decrease with 2 units / day
57 Diabetes Ketoacidosis What is Diabetes Ketoacidosis Watkins et al. In: Diabetes and its Management 2003  Acute decompensated metabolic state due to  severe insulin deficiency  over-activity of glucagon & other counter-regulatory hormone  Common in Type 1; Rare in Type 2  Potentially life-threatening  High mortality  Incidence : 5-8 /1000 diabetic persons/yr  Mortality rates 9-14 % - Has improved with insulin use 2%
58 How to Diagnose Diabetes Ketoacidosis  Anorexia  Nausea  Vomiting  Thirst  Polyuria  Weakness  Abdominal pain  Weight loss  Tachycardia  Hypotension  Hypothermia  Impaired consciousness  Warm dry skin  Kussmaul respiration  Acetone odour on breath Symptoms Signs Why are patients developing ketoacidosis The most common events that cause a person with diabetes to develop diabetic ketoacidosis are:  infection such as diarrhea, vomiting, and/or high fever (40%)  missed or inadequate insulin (25%)  newly diagnosed or previously unknown diabetes (15%)  Various other causes may include a heart attack, stroke, trauma, stress, alcohol abuse, drug abuse, and surgery.  Approximately 5% to 10% of cases have no identifiable cause
59 Diabetes Ketoacidosis Definitions Diabetes Care, Vol. 29, Number 12, December 2006 DKA is defined as:  Increase serum concentration of ketones greater than 5 mEq/L (beta hydroxybutirate acid > 0,6)  Blood glucose level greater than 250 mg/dL (although it is usually much higher),  Blood pH less than 7.3  Ketonemia and ketonuria are characteristic, as is a serum bicarbonate level of 18 mEq/L or less (< 5 mEq/L is indicative of severe DKA) Objectives and Management of DKA Treatment 1. Search & treat precipitating cause 2. Replacing fluids 3. Insulin iv (rapid / short- acting) 4. Replacing electrolytes - potassium & magnesium- if required 5. For GPs: If you observe a DKA case, immediately send the patient to the hospital 1. To normalize blood glucose as soon as possible with Insulin 2. To replace fluids and reverse ketoacidosis 3. Monitoring: • Vital signs • Fluid and electrolyte balance • Glycaemia Objectives Management
60 Initial DKA Treatment in Primary Care 1. Evaluate vital signs and urine volume 2. IV line, start the rehydration 3. Check the blood glucose periodically (per hour if possible) Prepare the patient for Hospital 12:00 12:30 1:00 2:00 30 min. 30 min. 60 min. • Start insulin with bolus IV 180 mU/kgBW, and continue with insulin drip 90 mU/hour/kgBW • Check blood glucose per hour with glucometer on the way to hospital Diabetes Acute Complication – Hypoglycemia and DKA Lecture Main Learning Points • Understand the hypoglycemia mechanism and how hypoglycemia should be treated • Understand how to adjust OAD - or insulin dosage after hypoglycemic events • Understand what causes a DKA event, how DKA is treated and what to do if you experience a patient with DKA Summary • The risk of hypoglycemia is one of the key limiting factors in reaching optimal glucose targets • For Insulin, hypoglycemia is mainly a phenomenon occurring in Type 1 diabetes patients • Prevention of hypoglycemia requires patient education, frequent blood glucose monitoring and exercise planning • If hypoglycemia occur repeatedly, reduce the dosage of OAD and/or Insulin • DKA should be regarded as an emergency situation and prompt treatment with insulin is vital
61 Initiating Diabetes Treatment with OADs Lecture: 30 minutes Initiating Diabetes Treatment with OADs Lecture Main Learning Points • Understand the different classes of OADs and when to use which OADs – either as mono therapy or in combination with other OAD’s / Insulin
62 Factors to Consider when Choosing an Anti- hyperglycemic agent Effectiveness in lowering glucose Extraglycaemic effects that may reduce long-term complications Safety profile Tolerability Cost Effect on body weight Nathan DM et al. Diabetes Care 2006;29(8):1963-72. Treatment therapies for Type 2 diabetes When and How to start treatment Adapted from Raccah et al. Diabetes Metab Res Rev 2007;23:257. Lifestyle + Metformin +-other OAD or GLP-1 agonists HbA1c ≥7.0% Basal Basal Insulin Premix Insulin Basal + Bolus Insulin START TREATMENT OAD TREATMENT START INSULIN INSULIN INTENSIFICATION
63 Updated PERKENI Type 2 Diabetes Treatment Algorithm Diabetes STEP 1 STEP 2 STEP 3 Healthy life style Healthy life style + Mono therapy Healthy life style + 2 OAD Combination Healthy life style + Combination 2 OAD + Basal insulin Insulin Intensification* *Intensive Insulin: use of basal insulin together with insulin prandial Healthy life style + 3 OAD Combination Alternative option, if : • No insulin is available • The patient is objecting insulin • Blood glucose is still not optimally controlled Note: 1. Therapy failed if target of HbA1c < 7% is not achieved within 2-3 months for each step 2. In case of no HbA1c test, the use of blood glucose level is also permitted. Average blood glucose level for a few BG test in one day can be converted to HbA1c (ref: ADA 2010) Updated PERKENI Type 2 Diabetes Treatment Algorithm
64 ADA/EASD Algorithm Main pathophysiological defects in type 2 DM hepatic glucose production peripheral glucose uptake pancreatic insulin secretion pancreatic glucagon secretion gut carbohydrate delivery and absorption incretin effect Hyperglycemia ? Liver Muscle PancreasIntestines Adipose Brain Kidney Glucose reabsorpsion Adapted from:Inzucchi SE, Sherwin RS. Diabetes Mellitus. In: Goldman L, Ausiello D, eds. Cecil Textbook of Medicine. 23rd Edn. Philadelphia, Pa: Saunders Elsevier; 2007.
65 Current available OADs and non-Insulin injectables in Indonesia • Metformin • Sulfonylureas (SUs) and glinides • α-glucosidase inhibitors (AGIs) • Glucagon-like peptide-1 (GLP-1) agonists • Thiazolidinediones (TZDs) • Dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) Metformin Mode of Action The primary effects of metformin are to decrease hepatic glucose production and increase insulin-mediated peripheral glucose uptake  Anaerobic glucose metabolism  Glucose uptake Adipose tissueMuscle Liver  Glucose uptake  Glucose oxidation Glucose oxidation  Glycogenesis Intestine  Oxidation of FA  Gluconeogenesis  Glycogenolysis  Oxidation of FA Krentz AJ, Bailey CJ. Drugs 2005;65:385–411. FA: Fatty Acids
66 Metformin Clinical Overview and Contraindications Metformin Efficacy* Safety, Tolerability and Adherence Contraindications Advantages • HbA1c reduction of 1-2% • FPG reduction of 40-70 mg/dl • Associated with diarrhea and abdominal discomfort • Lactic acidosis if improperly prescribed • Renal insufficiency • Liver failure • Heart failure • Severe gastrointestinal disease • Do not cause hypoglycaemia when used as mono-therapy • Do not cause weight gain; may contribute to weight loss Krentz AJ, Bailey CJ. Drugs 2005;65:385–411. * Efficacy depends on existing blood glucose levels Metformin Little benefit – if any - to go above 2.000 mg Fasting Plasma Glucose HbA1c 61.9 77.9 40.9 31.0 18.9 0 10 20 30 40 50 60 70 80 Changevs.Placebo(mg/dl) 2500mg2000mg1500mg1000mg500mg Garber AJ, Am J Med 1997;102:491-7. Metformin Dose 1.6 2.0 1.7 1.2 0.9 0.0 0.5 1.0 1.5 2.0 Changevs.Placebo(%) 2500mg2000mg1500mg1000mg500mg Metformin Dose
67 SUs and Glinides Mode of Action • Sulfonylureas (SUs) and glinides increase endogenous insulin secretion by binding to pancreatic β-cells and triggering a cascade of intracellular events1–3 • The mode of action of SUs and glinides is similar, but stimulation of insulin secretion is more rapid and short-acting with glinides • SU receptors are also found on other cells, including the cardiac myocytes 1. Gallwitz B, Haring H-U. Diabetes Obes Metab 2010;12:1–11. 2. Schuit FC, et al. Diabetes 2001;50:1–11. 3. Krentz AJ, Bailey CJ. Drugs 2005;65:385–411. SU: sulfonylurea; GLUT: glucose transporter. Pancreatic β-cell Glucose uptake Insulin release Voltage-gated calcium channel ATP-sensitive potassium channel SUs / glinides Glycolysis respiration Glucokinase ATP Ca2+ ATP = orange Ca2+ = light green SUs and Glinides Clinical Overview Sulphonylurea Efficacy* Safety, Tolerability and Adherence • HbA1c reduction of 1-2% • FPG reduction of 40-70 mg/dl • Associated with hypoglycaemia and weight gain Krentz AJ, Bailey CJ. Drugs 2005;65:385–411. Nathan DM, et al. Diabetologia. 2009;52:17–30. Rosenstock J, et al. Diabetes Care. 2004;27:1265–70. * Efficacy depends on existing blood glucose levels Glinides Efficacy* Safety, Tolerability and Adherence • HbA1c reduction of 0.5-1.5% • FPG reduction of 20-60 mg/dl • PPG reduction of 75-100 mg/dl • Associated with hypoglycaemia and weight gain • Frequent administration (with every meal) is required.
68 Alpha glucosidase inhibitors Mode of Action • Slow digestion of sucrose and starch and therefore delay absorption • Slow post-meal rise in blood glucose • Side effects • Flatulence, abdominal discomfort , diarrhoea • As mono-therapy will not cause hypoglycaemia • Hypoglycaemia when used with other medicine (e.g. a sulphonylurea) 1. Gallwitz B, Haring H-U. Diabetes Obes Metab 2010;12:1–11. 2. Schuit FC, et al. Diabetes 2001;50:1–11. 3. Krentz AJ, Bailey CJ. Drugs 2005;65:385–411. Alpha glucosidase inhibitors Clinical Overview Alpha glucosidase inhibitors Efficacy* Safety, Tolerability and Adherence • HbA1c reduction of 0.5-1% • FPG reduction of 10-20 mg/dl • PPG reduction of 40-50 mg/dl • Associated with flatulence, diarrhea and abdominal discomfort • As mono-therapy will not cause hypoglycaemia • Frequent administration (with every meal) is required. Krentz AJ, Bailey CJ. Drugs 2005;65:385–411. Nathan DM, et al. Diabetologia. 2009;52:17–30. Rosenstock J, et al. Diabetes Care. 2004;27:1265–70. * Efficacy depends on existing blood glucose levels
69 Thiazolidinediones (TZDs) Mode of Action Thiazolidinediones (TZDs) increase the sensitivity of muscle and adipose cells to insulin and suppressing hepatic glucose production Krentz AJ, Bailey CJ. Drugs 2005;65:385–411. TZD: Thiazolidinediones  Glucose uptake  Glucose uptake  Gluconeogenesis *Inconsistent findings Adipose tissue Muscle Liver  Fatty acid uptake  Lipogenesis  Pre-adipocyte differentiation  Glycolysis  Glucose oxidation  Glycogenesis*  Glycogenolysis  Lipogenesis  Glucose uptake* Thiazolidinediones Clinical Overview Krentz AJ, Bailey CJ. Drugs 2005;65:385–411. Drug Class Review: Thiazolidinediones. Available at: http://pharmacy.oregonstate.edu/drug_policy/pages/dur_board/reviews/articles/TZD_ClassReview.pdf . Rizzo M, et al. Expert Opin Pharmacother. 2008;9:2295–303. * Efficacy depends on existing blood glucose levels Thiazolidinediones Efficacy* Safety, Tolerability and Adherence Contraindications Advantages • HbA1c reduction of 0.5-1.5% • FPG reduction of 20-55 mg/dl • Associated with weight gain and edema • Contraindicated in patients with abnormal liver function • Warnings regarding risk of fractures • May exacerbate or precipitate congestive heart failure • Liver disease, heart failure or history of heart disease • Pregnancy and breast feeding • Reduced levels of LDL- cholesterol and increased level of HDL- cholesterol
70 DPP-4 inhibitors Mode of Action Drucker DJ et al. Nature 2006;368:1696–705. Idris I, et al. Diabetes Obes Metab 2007;9:153–65. Barnett A. Int J Clin Pract 2006;60:1454–70. Gallwitz B, et al. Diabetes Obes Metab 2010;12:1–11. DPP-4: dipetidyl peptidase-4; GI: gastrointestinal; GIP:glucose-dependent insulinotropic polypeptide; GLP-1: glucagon-like peptide Increases and prolongs GLP-1 effect on α-cells Increases and prolongs GLP-1 and GIP effects on β-cells Food intake Stomach GI tract Intestine α-cells Pancreas Glucose-dependent insulin secretion β-cells DPP-4 inhibitor Glucose-dependent glucagon secretion Incretins (GLP-1, GIP) DPP-4 Net effect: blood glucose * GIP does not inhibit glucagon secretion by α-cells DPP-4 inhibitors Clinical Overview DPP-4 inhibitors Efficacy* Safety, Tolerability and Adherence • HbA1c reduction of 0.5-1% • FPG reduction of 20 mg/dl • PPG reduction of 45-55 mg/dl • Generally well tolerated • Low risk of hypoglycemia • Not associated with weight gain • Upper respiratory tract infection5 has been reported in clinical studies • Most require only once daily administration Ahrèn B. Expert Opin Emerg Drugs 2008;13:593–607. Gallwitz B, et al. Diabetes Obes Metab 2010;12:1–11. Amori RE, et al. JAMA 2007;298:194–206. Saxagliptin, FDA’s Endocrinologic and Metabolic Drugs Advisory Committee Briefing Document for April 2009 Meeting: NDA 22-350. Available at: http://www.fda.gov/OHRMS/DOCKETS/ac/09/briefing/2009-4422b1-02-Bristol.pdf. (accessed Nov 2010). Aschner P, et al. Diabetes Care 2006;29:2632–7. * Efficacy depends on existing blood glucose levels
71 GLP 1 Agonist Mode of Action 1. Doyle ME, Egan JM. Pharmacol Ther 2007;113(3):546–93. GLP-1: glucagon-like peptide Glucagon-like peptide-1 (GLP-1) agonist activates the GLP receptor in the pancreas. This increases insulin release from the pancreatic β-cells, while inhibiting glucagon release by the pancreatic α-cells α-cell Pancreas • Glucose-dependent insulin biosynthesis and secretion • β-cell proliferation β-cells • Glucagon secretion • β-cell apoptosis GLP-1 agonist Net effect: blood glucose GLP 1 Agonist Clinical Overview GLP-1 Agonist Efficacy* Safety, Tolerability and Adherence • HbA1c reduction of 1-2% • FPG reduction of 6-12 mg/dl • PPG reduction of 6-18 mg/dl • Associated with moderate and transient nausea, vomiting and diarrhoea • Low risk of hypoglycemia and no evidence of increased CV risk • Associated with weight reduction • Associated with reduction in BP Garber AJ. Diabetes Care 2011;34 (Suppl 2):S279–84. Moretto TJ, et al. Clin Ther 2008;30:1448–60. Drucker DJ. Cell Metab 2006;3:153–65. Amori RE, et al. JAMA 2007;298:194–206. * Efficacy depends on existing blood glucose levels
72 The Principles of OAD Combination Theory • Two (or more) oral blood glucose-lowering medicines that have different mechanisms of action • Two medications is better rather than increase in initial medicine to maximum dosage • Fewer side effects than mono-therapy at higher doses Diabetes in elderly people • Always start with the lowest dose of any blood glucose-lowering medicine and increase gradually • Using shorter-acting medicines that reduces the risk of hypoglycaemia • Hypoglycaemia may increase the risk of falls and heart attack in older people  Remember the possibility of • Forgetfulness • Poor motivation • Depression • Cognitive deficits • Poly-pharmacy • Reduced manual dexterity • These factors impact on the ability to maintain self-care and achieve maximum benefits from blood glucose-lowering medicines.
73 OAD’s – a quick summary of the different mechanism of actions α-Glucosidase inhibitors Delay intestinal carbohydrate absorption Thiazolidinediones Increase glucose uptake in skeletal muscle and decrease lipolysis in adipose tissue Sulfonylureas Increase insulin secretion from pancreatic β-cells GLP = glucagon-like peptide. Adapted from Cheng and Fantus. CMAJ. 2005;172:213–226. Meglitinides Increase insulin secretion from pancreatic β-cells Incretins :GLP-1 analogue(exen- atide)/DPP-4 inhibitors Improves glucose-dependent insulin secretion from pancreatic β-cells, suppresses glucagon secretion from α-cells, slows gastric emptying Properties of available glucose-lowering agents that may guide treatment choice in Type 2 Diabetes Class Compounds(s) Cellular mechanism Primary Physiological action(s) Advantages Disadvantages Biguanides Metformin Activates AMP-kinase Hepatic Glucose Production ↓ Extensive Experience No weight gain No hypoglycaemia Likely CVD Events ↓ Gastrointestinal side effects Lactic acidosis risk (rare) Vitamin B12 deficiency Multiple contraindications: CKD, acidosis, hypoxia, dehydration etc. Sulfonylureas Glibenclamide / glyburide Glipizide Gliclazide Glimepiride Closes KATP channels on beta cell plasme membranes Insulin secretion ↑ Extensive experience Microvascular Risk ↓ (UKPDS) Hypoglycemia Weight gain Blunts myocardial ischaemic preconditioning ? Low durability Meglitinides Repaglinide Nateglinide Closes KATP channels on beta cell plasme membranes Insulin secretion ↑ Postprandial glucose excursions ↓ Dosing flexibility Hypoglycemia Weight gain Blunts myocardial ischaemic preconditioning ? Frequent dosing schedule Inzucci SE, et al. Diabetologia. 2012
74 Properties of available glucose-lowering agents that may guide treatment choice in Type 2 Diabetes cont. Class Compounds(s) Cellular mechanism Primary Physiological action(s) Advantages Disadvantages Thiazolidinedi ones Pioglitazone Rosiglitazone Activates the nuclear transcription factor PPAR-y Insulin Sensitivity ↑ No hypoglycaemia Durability HDL-C ↑ Triacylglycerol ↓ (pioglitazone) CVD Events ↓? Weight Gain Oedema / Heart Failure Bone Fractures LDL-C ↑ (rosiglitazone) Mn ↑ (meta- analyses, rosiglitazone) Bladder Cancer ↑? (pioglitazone) a-Glucosidase Inhibitors Acarbose Migitol Voglibose Inhibits intestinal a- glucosidase Slows intestinal carbohydrate digestions / absorption No hypoglycaemia Postprandial glucose excursions ↓ CVD Events ↓ Non-systemic Modest HbA1c efficacy Gastrointestinal side effects (flatulence, diarrhoea) Frequent dosing schedule DPP-4 Inhibitors Sitagliptin Vildagliptin Saxagliptin Linagliptin Alogliptin Inhibits DPP-4 activity, increasing postprandial active incretin (GLP-1, GIP) concentrations Insulin secretion ↑ (glucose-dependent) Glucagon secretion ↓ (glucose-dependent) No hypoglycaemia Well tolerated Modest HbA1c efficacy Urticardia/Angio- oedema Pancreatitis ? Inzucci SE, et al. Diabetologia. 2012 Properties of available glucose-lowering agents that may guide treatment choice in Type 2 Diabetes cont. Class Compounds(s) Cellular mechanism Primary Physiological action(s) Advantages Disadvantages GLP-1 Receptor Agents Exenatide Liraglutide Activates GLP- 1 receptors Insulin secretion ↑ (glucose-dependent) Glucagon secretion ↓ (glucose-dependent) Slows gastric emptying Satiety ↑ No hypoglycaemia Weight reduction Improved beta cell mass / function ? Cardiovascular protective actions ? Gastrointestinal side effects (nausea / vomiting) Acute pancreatitis ? C cell hyperplasia / medullary thyroid tumours Injectable Training Requirements Insulin Human NPH Human Regular Lispro Aspart Gluisine Glargine Determir Pre-mixed (several types) Activates insulin receptors Glucose disposal ↑ Hepatic glucose production ↓ Universally effective Theoretically unlimited efficacy Microvascular Risk ↓ (UKPDS) Hypoglycemia Weight gain Mitogenic effects ? Injectable Training Requirements ‘Stigma’ for patients Inzucci SE, et al. Diabetologia. 2012
75 Initiating Diabetes Treatment with OADs Lecture Main Learning Points • Understand the different classes of OADs and when to use which OADs – either as mono therapy or in combination with other OAD’s / Insulin Summary • Different start and intensification options for OADs exist depending on the need for the individual patient • Metformin will generally be the first drug of choice
76 Propertiesofavailableglucose-loweringagentsthatmay guidetreatmentchoiceinType2Diabetes ClassCompounds(s)Cellular mechanism Primary Physiological action(s) AdvantagesDisadvantages BiguanidesMetforminActivates AMP-kinase HepaticGlucose Production↓ Extensive Experience Noweightgain Nohypoglycaemia LikelyCVDEvents↓ Gastrointestinalside effects Lacticacidosisrisk (rare) VitaminB12 deficiency Multiple contraindications: CKD,acidosis, hypoxia, dehydrationetc. SulfonylureasGlibenclamide/ glyburide Glipizide Gliclazide Glimepiride ClosesKATP channelson betacell plasme membranes Insulinsecretion↑Extensive experience MicrovascularRisk↓ (UKPDS) Hypoglycemia Weightgain Bluntsmyocardial ischaemic preconditioning? Lowdurability MeglitinidesRepaglinide Nateglinide ClosesKATP channelson betacell plasme membranes Insulinsecretion↑Postprandial glucoseexcursions↓ Dosingflexibility Hypoglycemia Weightgain Bluntsmyocardial ischaemic preconditioning? Frequentdosing schedule InzucciSE,etal.Diabetologia.2012
77 Propertiesofavailableglucose-loweringagentsthatmay guidetreatmentchoiceinType2Diabetescont. ClassCompounds(s)Cellular mechanism Primary Physiological action(s) AdvantagesDisadvantages Thiazolidinedi ones Pioglitazone Rosiglitazone Activatesthe nuclear transcription factorPPAR-y InsulinSensitivity↑No hypoglycaemia Durability HDL-C↑ Triacylglycerol↓ (pioglitazone) CVDEvents↓? WeightGain Oedema/Heart Failure BoneFractures LDL-C↑ (rosiglitazone) Mn↑(meta- analyses, rosiglitazone) BladderCancer↑? (pioglitazone) a-Glucosidase Inhibitors Acarbose Migitol Voglibose Inhibits intestinala- glucosidase Slowsintestinal carbohydrate digestions/ absorption No hypoglycaemia Postprandial glucose excursions↓ CVDEvents↓ Non-systemic ModestHbA1c efficacy Gastrointestinalside effects(flatulence, diarrhoea) Frequentdosing schedule DPP-4 Inhibitors Sitagliptin Vildagliptin Saxagliptin Linagliptin Alogliptin InhibitsDPP-4 activity, increasing postprandial activeincretin (GLP-1,GIP) concentrations Insulinsecretion↑ (glucose-dependent) Glucagonsecretion↓ (glucose-dependent) No hypoglycaemia Welltolerated ModestHbA1c efficacy Urticardia/Angio- oedema Pancreatitis? InzucciSE,etal.Diabetologia.2012
78 Propertiesofavailableglucose-loweringagentsthatmay guidetreatmentchoiceinType2Diabetescont. ClassCompounds(s)Cellular mechanism Primary Physiological action(s) AdvantagesDisadvantages GLP-1 Receptor Agents Exenatide Liraglutide ActivatesGLP- 1receptors Insulinsecretion↑ (glucose-dependent) Glucagonsecretion↓ (glucose-dependent) Slowsgastric emptying Satiety↑ No hypoglycaemia Weightreduction Improvedbeta cellmass/ function? Cardiovascular protective actions? Gastrointestinalside effects(nausea/ vomiting) Acutepancreatitis? Ccellhyperplasia/ medullarythyroid tumours Injectable Training Requirements InsulinHumanNPH HumanRegular Lispro Aspart Gluisine Glargine Determir Pre-mixed (severaltypes) Activates insulin receptors Glucosedisposal↑ Hepaticglucose production↓ Universally effective Theoretically unlimited efficacy Microvascular Risk↓(UKPDS) Hypoglycemia Weightgain Mitogeniceffects? Injectable Training Requirements ‘Stigma’forpatients InzucciSE,etal.Diabetologia.2012
79 The Usage of Insulin Lecture Main Learning Points • Understand the insulin mechanism of action and its relationship to blood glucose • Understand the current usage of Insulin in Indonesia • Understand the different types of insulin, when to use insulin and the different insulin regiments • Understand the relationship between insulin dosage and blood glucose measurements Insulin Initiation and Monitoring Lecture: 30 minutes
80 Insulin remains the most efficacious glucose lowering agent Decrease in HbA1c: Potency of monotherapy HbA1c% Nathan et al., Diabetes Care 2009;32:193-203. IMS Full year 2011 Data. CIA World Factbook 29 67 92 Malaysia Thailand Vietnam Philippines 104 Bangladesh 161 Indonesia 248 Population Million People Mega Units Total Insulin Used 2,029 3,258 417 982 3,097 694 70 49 5 9 19 3 Insulin Usage per Capita Insulin Units / Capita …but Insulin usage is currently very low in Indonesia compared to its neighbouring countries
81 What is Insulin • After a meal carbohydrates are digested and enter the blood system, which transports them to the cells INSULIN is needed for glucose uptake and storage • Some cells (those of muscles and fat tissue) need assistance to have blood sugar enter into them and to be used for energy production • The liver needs assistance to start the process of storage of glucose in the form of glycogen …and our diabetes patients are not in good glycemic control DiabCare Indonesia 2008 illustrated the need for more intensive treatment to decrease FPG and PPG n: 1.823 patients with diabetes 208 144 100 140 0 20 40 60 80 100 120 140 160 180 200 220 mg/dl PPG (mg/dl)FPG (mg/dl) GlycemicControlLevel PERKENI GuidelinesDiabCare 2008 Source: Novo Nordisk Data on File
82 Insulin secretion is delayed and blunted in Type 2 Diabetes Adapted from: Polonsky KS, et al. N Engl J Med. 1996 Mar 21;334(12):777-783. Normal Type 2 diabetes Time (24 hours) 800 600 400 200 0 Insulin Secretion (pmol/min) Meal Meal Meal The goal of insulin therapy is to restore normal insulin secretion ‘Gap’ that needs to be covered How Insulin acts in the body Insulin Insulin binds to the insulin receptors on the cell membranes of the target cells in the liver, muscles and adipose tissue Liver Adipose Tissue Muscles • Inhibits glucose production • Promotes formation of glycogen and its storage • Promotes uptake and utilization of glucose • Promotes uptake of glucose • Suppresses lipolysis
83 …diabetes Patients will eventually fail on OAD’s 6.2% – upper limit of normal range MedianHbA1c(%) UKPDS 6 7 8 9 Years from randomisation Conventional* Glibenclamide Metformin Insulin 2 4 6 8 100 7.5 8.5 6.5 Recommended treatment target <7.0%† 8 6 7.5 7 6.5 Time (years) 0 2 3 4 51 ADOPT Metformin Glibenclamide Rosiglitazone *Diet initially then sulphonylureas, insulin and/or metformin if FPG>15 mmol/L; †ADA clinical practice recommendations. UKPDS 34, n=1704 UKPDS 34. Lancet 1998:352:854–65; Kahn et al (ADOPT). NEJM 2006;355(23):2427–43 Most people with type 2 diabetes will, in time, need insulin therapy Wright A et al. Diabetes Care 2002;25:330–6 (Patients treated with chlorpropramide) Years from start of UKPDS Patientsrequiring additionalinsulin(%) 0 10 20 30 40 50 60 1 2 3 4 5 6
84 Maintain blood glucose levels between 80-140 mg/dl: 1. By promoting uptake of glucose by target cells • subsequent breakdown into energy (glycolysis) • storage as glycogen (glycogenesis) 2. By inhibiting new glucose formation from non carbohydrate source (gluconeogenesis) or production of glucose by liver 3. By suppressing lipolysis (breakdown of fat) Objectives of Insulin Treatment Absolut Indication Type 1 Diabetes Relative Indication Patients who fail to reach target with OAD optimal dosage (3-6 months) Type 2 DM Outpatient with: Pregnancy not controlled with diet Infected Diabetes Feet High Blood Glucose Fluctuations Repeated History of Ketoacidosis History of Pankreotomi Besides the above, there are a number of conditions where insulin is required, e.g. chronic liver, kidney function interruption and high dosage steroid therapy Insulin Indications
85 Insulin can be initiated at any time… • Traditionally, insulin has been reserved as the last line of therapy… • …However, considering the benefits of normal glycemic status, Insulin can be initiated earlier. Inadequate Lifestyle + 1 OAD + 2 OAD + 3 OAD INITIATE INSULIN Adapted from Nathan DM, et al. Diabetes Care 2009; 31:193-203 ADA/EASD Guideline
86 Three Types of Insulin Schematic Representation OnlyGIR(mg/kg/min) Time (h) 0 4 8 12 16 20 24 BASAL INSULIN PRE-MIX INSULIN FAST-ACTING INSULIN Three Types of Insulin 1. Hompesch M. Diabetes Obes Metab 2006; 8:568; 2. Weyer et al. Diabetes Care 1997;10:1612–1614.; 3. 1. Heinemann et al. Diabetes Care. 1998;21:1910–4 Basal Insulin provides a steady concentration of insulin in the bloodstream over 24 hours. Initially, basal insulin should be given at 10 units per day at night time or in the morning1 Time (h) Premixed insulins contain a mixture of rapid-acting and intermediate-acting insulin in a fixed combination to provide coverage of prandial and basal insulin requirements2 Fast-acting insulins include single amino acid replacement that reduce their ability to self- associate into dimers and hexamers. This means that they are quickly absorbed into the bloodstream, following subcutaneous injection.3 FAST-ACTINGPRE-MIXBASAL GIR(mg/kg/min) 0 8 16 20 244 12 Time (h) GIR(mg/kg/min) 0 8 16 20 244 12 Time (h) GIR(mg/kg/min) 0 8 16 20 244 12
87 Basic Insulin Start Recommendation If Fasting Blood Glucose is elevated • Start with Basal Insulin If both Fasting and Prandial Blood Glucose are elevated • Start with Premix Insulin • OR add Basal Insulin to OAD • OR Start Basal/Bolus Therapy Source: ADA Guidelines Pharmacokinetics of the different Types of Insulin available in Indonesia Profile Type of Insulin Insulin Name Onset (hours) Peak (hours) Duration (hours) Fast-acting Analogue Insulin Insulin Aspart (NovoRapid) 0.2 – 0.5 0.5 - 2 3 - 5 Insulin Lispro (HumaLog) 0.2 – 0.5 0.5 - 2 2 - 4 Insulin Gluisine (Apidra) 0.2 – 0.5 0.5 - 2 1 – 2.5 Fast-acting Human Insulin ActRapid 0.5 – 1 0.5 - 1 3 – 6 Humulin R 0.5 – 1 0.5 - 1 3 - 6 Intermediate Human Insulin Insulatard 1.5 – 4 4 - 10 10 – 16 Humulin N 1.5 – 4 4 - 10 10 - 16 Long-acting Analogue Insulin Insulin Detemir (Levemir) 1 - 3 Up to 24 Insulin Glargine (Lantus) 1 - 3 Up to 24 Pre-mix Analogue Insulin Insulin Aspart (NovoMix) 0.2 – 0.5 1 - 4 10 -16 Insulin NPL (HumaLog) 0.2 – 0.5 1 - 4 10 -16 Pre-mix Human Insulin Mixtard 0.5 – 1 3 - 12 10 - 16 Humulin Mix 0.5 – 1 3 - 12 10 – 16 Adapted from Mooradian et al. Ann Intern Med 2006; 145: 125-34
88 Insulin Titration schemes Basal and Fast-Acting Insulin Fasting Blood Glucose Content (mg/dl) Basal Insulin Titration <70 mg/dl Reduce dosage with 2 units 70-130 mg/dl Maintain dosage 130-180 mg/dl Increase dosage 2 units per 3 days >180 mg/dl Increase dosage 4 units per 3 days Once titrated, continue to monitor HbA1c every 3 months BASAL INSULIN Subsequent pre-meal Glucose (mg/dl) Fast-acting Insulin Titration Start with 4 units / day Increase by 2 units every 3 days until target is reached When starting Fast-acting Insulin, secretagogues should be discontinued FAST- ACTING INSULIN Source: KONSENSUS: Insulin Treatment 2011 Insulin Treatment Optimization How to Optimize Treatment after Initiation Basal Insulin Only Usually with OAD Start with Basal Insulin 10u / daily with meal or before bedtime. Same injection time every day If glycemic target is not reached within 2-3 months, intensify Insulin treatment If glycemic target is not reached titrate according to Basal Titration Scheme Basal Insulin Only Usually with OAD Basal with Prandial Usually keep Metformin Premix Insulin Usually keep Metformin Basal Bolus Usually keep Metformin Add Prandial starting with 4u / day either once or twice-daily and titrate accordingly Switch to Premix twice-daily. Start with equal basal dose, but give 50% per injection and titrate accordingly Switch to Basal Bolus (3 daily prandial) start with 4u / day and titrate accordingly) Source: PERKENI Insulin Guidelines 2011
89 Primarily one type of Insulin device available in Indonesia • Disposable – disposed of once empty • Less teaching time required • Primarily plastic • Easy and Convenient for Patients Prefilled devices
90 Slide1 Skematitrasiinsulin InsulinBasaldanFast-Acting GlukosaDarahPuasa (mg/dl) TitrasiInsulinBasal <70mg/dlKurangidosissebesar2unit 70-130mg/dlPertahankandosis 130-180mg/dlTingkatkandosis2unitper3hari >180mg/dlTingkatkandosis4unitper3hari Setelahdititrasi,lanjutkanmonitorHbA1csetiap3bulan INSULIN BASAL GlukosaDarahPuasa (mg/dl)TitrasiInsulinFast-acting Mulaidengan4unit/hari Tingkatkandosis2unitsetiap3 harisampaitargettercapai KetikamulaimenggunakanFast-actingInsulin,pemebrian secretagoguesharusdihentikan INSULIN FAST- ACTING
91 Slide2 Skematitrasiinsulin InsulinPre-mix KadarGlukosaDarah sebelummakanpagiatau makanmalam(mg/dl) TitrasiInsulinPre-mix <72mg/dlKurangidosis4unit 72-126mg/dlPertahankandosis 126-144mg/dlTingkatkandosis2unit >144mg/dlTingkatkandosis4unit Selamatitrasi,ukurkadarglukosadarahpuasadanglukosa post-prandialpagidanmalamharisetiap2hari.Ketika targettercapaimonitor1-2xsetiapminggu INSULIN PRE-MIX ¥ Dosisinsulinmalamharidititrasiberdasarkankadarglukosadarahpuasa ¥ Dosisinsulinpagiharidititrasiberdasarkandosissebelummakanmalam ¥ Disarankanpasienuntukmentitrasidosisinsulinmalamterlebihdahuludiikuti dengandosispagi ¥ Penyesuaiandosispalingcepatsetiap3hari
92 Screening, Treatment and Evaluation of Complications Lecture: Screening, Treatment and Evaluation of Complications Lecture Main Learning Points • Understand the screening, diagnose and treatment options / refer for diabetes associated complications: • Nephropathy • Retinopathy • Neuropathy • Erectile Dysfunction • CVD • CAD
93 Recap: The goal of diabetes management is to secure optimal glycemic control to avoid complications Diabetic retinopathy Leading cause of blindness in working-age adults1 Diabetic nephropathy Leading cause of end-stage renal disease2 Cardiovascular disease Stroke 1.2- to 1.8-fold increase in stroke3 Diabetic neuropathy Leading cause of non-traumatic lower extremity amputations5 75% diabetic patients die from CV events4 1Fong DS, et al. Diabetes Care 2003;e 26 (Suppl.1):S99–S102. 2Molitch ME, et al. Diabetes Care 2003; 26 (Suppl.1):S94–S98. 3Kannel WB, et al. Am Heart J 1990; 120:672–676. 4Gray RP & Yudkin JS. Textbook of Diabetes 1997. 5Mayfield JA, et al. Diabetes Care 2003; 26 (Suppl.1):S78–S79. Microvascular Macrovascular Diabetic Foot Erectile Dysfunction The most secretive Complication of DM Recap: Risk of Complications increases as Hb1Ac increases Stratton IM et al. BMJ 2000;321:405–12 0 20 40 60 80 5 6 7 8 9 10 11 Myocardial infarction Microvascular disease Updated Mean HbA1c (%) Adjusted for age, sex, and ethnic group Incidenceper1.000 patient-years
94 Recap: It’s the diabetes-related complications – not the diabetes medicine - that carries the biggest cost to the society Cost increases with a factor of 22.5 if patients develop complications (ASKES Data) 900 40 0 100 200 300 400 500 600 700 800 900 US$ With ComplicationsWithout Complications Approximate Annual Cost / Diabetes Patient ASKES 2010 Unpublished data 22.5X Positive legacy effect of earlier glucose control Provides long-term reductions in both microvascular and macrovascular complications 15% p=0.01 24% p=0.001 13% p=0.007 9% p=0.04 Any diabetes endpoint Microvascular disease Myocardial infarction Death (any cause) 16% p=0.052 25% p=0.0099 6% p=0.44 12% p=0.03 RRR* at end of UKPDS RRR* at end F/U (median 8.5 years) RRR: relative risk reduction of intensive therapy over conventional therapy UKPDS 80. Holman et al. NEJM 2008; 359:1577-89.
95 Classification of Micro- and Macrovascular Complications Chronic complications of diabetes • Microvascular complications • Kidney – nephropathy » kidney failure • Eyes – retinopathy » blindness • Nerves – neuropathy » disability • Peripheral Arterial Diseases » disability • Erectile Dysfunction • Macrovascular complications • Heart – myocardial infarction • Brain – stroke • Atherosclerosis – myocardial infarction Microvascular Complications – an overview Retinopathy and blindness Nephropathy Neuropathy International Diabetes Federation. Diabetes Atlas 2006;111–2 Erectile Dysfunction
96 Diabetes Nephropathy Characteristics • Persistent albuminuria • Diabetic retinopathy • Hypertension • Decline in kidney function (about 12 ml/min/year) Diabetes Nephropathy Prevention and Treatment DCCT. Diabetes 1996;45:1289–98 Glycated haemoglobin (%) 5 8 12 0.0 0.4 0.8 0.6 0.2 111096 7 Probabilityof microalbuminuria • Maintain tight glycaemic and blood pressure control • Multifactorial disease management: • antihypertensive agents • good blood glucose control • control of dyslipidaemia • monitoring renal function • lifestyle changes, including smoking cessation and low-protein diet
97 Micro / Macro-albuminuria 24h: 30 - 299 mg/24h >300 mg/24h Random spot: 30 - 299 mcg/mg >300 mcg/mg Morning spot: 30 – 299 mcg/mg >300 mcg/mg Dipstick/overnight albumin: low sensitivity and specificity Micro Macro In 2 of 3 measurements Natural history of diabetic nephropathy . Functional GFR - (90-95%) Microalbuminuria, hypertension Proteinuria, nephrotic syndrome, GFR ¯ Urinary protein excretionGFR Urinaryproteinexcretion(mg/d) Years Glomerularfiltrationrate(GFR) (mL/min) 0 150 100 50 5 10 15 20 25 20 200 1000 5000 Incipient diabetic nephropathy Pre Overt diabetic nephropathy End-stage renal disease 1 2 3 4 5 Vora JP, et al. In: Johnson RJ, Feehally J, eds. Comprehensive Clinical Nephrology. New York: Mosby; 2000
98 Diabetes Retinopathy Non- Diabetic Retina Diabetic Maculopathy Proliferative Diabetic Retinopathy Treating Albuminuria • Use ACE-I or ARB in nonpregnant patiens with micro- or macroalbuminuria • Reduce protein intake to 0.8-1.0 g/kgBW/day in DM & early CKD; 0.8 g/kgBW/day in later CKD • If ACE-Is /ARBs/diuretics are given, monitor serum creatinine and potassium • When eGFR <60 ml/min/1.73m2, evaluate for CKD complications • Consider referral to experienced physician in kidney disease care Diabetes Care. 2012
99 Diabetes Retinopathy Risk Factors and Classification • Poor glycaemic and blood pressure control increase the risk of retinopathy • Five categories: • Mild Nonproliferative • Moderate Nonproliferative • Severe Nonproliferative • proliferative • advanced diabetic eye disease • maculopathy Chaturvedi et al. Diabetes Care 2001;24:284–9 London HbA1c (%) Retinopathyincidence(oddsratio) 4 6 9 0 5 10 875 35 30 25 20 15 10 DCCT HbA1c (%) 5.7 7.7 10.89.88.86.7 11.9 Diabetes Retinopathy Prevention and Treatment • Maintain tight glycaemic and blood pressure control • Regular eye examinations • Treat with laser photocoagulation and vitreoretinal surgery Klein et al. Ann Intern Med 1996;124:90–6
100 Diabetes Neuropathy Risk Factors and Common Types • Hyperglycaemia is the leading cause of diabetic neuropathy • Alcohol makes neuropathy worse • A number of clinical syndromes are recognisable Watkins et al. In: Diabetes and Its Management 2003. Pickup & Williams. In: Slide Atlas of Diabetes 2004 Pickup & Williams. In: Slide Atlas of Diabetes 2004 Symmetrical diffuse sensorimotor neuropathy Femoral neuropathy (amyotrophy) Other acute mononeuropathies Pressure palsies Sensory loss 0 → +++ Pain + → +++ Tendon reflexes N → ↓ Motor deficit 0 → + Sensory loss 0 → + Pain + → +++ Tendon reflexes ↓ → 0 Motor deficit + → +++ Sensory loss 0 → + Pain + → +++ Tendon reflexes N Motor deficit + → +++ Sensory loss + → +++ Pain + → ++ Tendon reflexes N Motor deficit + → +++ VIIII Truncal Ulnar Median Lateral popliteal Diabetes Neuropathy The Most Frequent Diabetes related Complication in Indonesia (and in the World…) Note: One patient can have more than one complication 6.7% 16.1%19.1%21.7% 41.9% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Neuropathy EyeCV Renal Foot Ulcer Frequency of complications A1Chieve Indonesia (2.240 patients) 8.7% 26.5% 33.4% 54.0% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Neuropathy Eye Renal Foot Ulcer Frequency of complications IDMPS Indonesia (715 patients)
101 Diabetic Foot Complications Diabetes Neuropathy Prevention and Treatment • Maintain tight glycaemic control to reduce the risk or progression of neuropathy • Exclude or treat contributory factors: • alcohol excess • vitamin B12 deficiency • uraemia • Offer pain relief based on the dominant symptoms DCCT. NEJM 1993;329:977–86 16 8 0 0 Percentageofcasesaffected p<0.001 12 4 Conventional therapy Intensified therapy 1 Time (years) 2 3 4 5
102 Erectile Dysfunction Definition ED is the inability to achieve and maintain an erection adequate for intercourse to the mutual satisfaction of the man and his partner. Remember, both partners in a relationship are affected Erectile Dysfunction Background • 35%-75% of men with diabetes will experience at least some degree of ED • Men with diabetes tend to develop erectile dysfunction 10 to 15 years earlier than men without diabetes. • Men with diabetes will have ED • 50%-60% in > 50 years old • 95% in >70 years old
103 Erectile Dysfunction Risk Factors  Risk Factors  Neuropathy  Peripheral vascular disease  Poor glycemic control  Diabetes duration and complications  Age and high BMI  Smoking doubles the risk Erectile Dysfunction Screening Rosen RC, Cappelleri JC, Smith MD, et al. Development and evaluation of an abridged, 5-item version of the International Index of Erectile Function (IIEF-5) as a diagnostic tool for erectile dysfunction. Int J Impot Res. 1999 Dec;11(6):319-26
104 MACRO VASCULAR COMPLICATION Erectile Dysfunction Treatment Options • Oral medications: Sildenafil (Viagra), Vardenafil (Levitra), Tadalafil (Cialis) • Urethral suppositories (MUSE) • Injection therapy: Caverject, Trimix, Bimix • Vacuum constriction device • Surgery • Sex therapy
105 Macrovascular Complications – an overview Stroke Cardiovascular/heart disease Peripheral vascular disease Cardiovascular Diseases Patients with Type 2 Diabetes at a increased risk of CVD • Risk of cardiovascular disease is greater in patients with diabetes than in those without • Having diabetes results in a similar risk of heart attack as a prior heart attack Incidence of myocardial infarction over 7 years Haffner et al. N Engl J Med 1998;339:229–34 With diabetes n=1059 Without diabetes n=1373 Patients(%)
106 Cardiovascular Diseases Risk for Myocardial infaction and stroke increases with progression to Type 2 Diabetes Adapted from Hu et al. Diabetes Care 2002; 25:1129-34 Relative risk for MI and stroke in women *Nurses’ Health Study (NHS) cohort comprised women only Relativerisk No diabetes during study Prior to diagnosis After diagnosis Diabetic at baseline Prevention of Cardiovascular Diseases Adapted from Stamler et al. Diabetes Care 1993;16:434–44 • Reduce risk factors for cardiovascular disease: • stop smoking • treat hypertension • treat hyperlipidaemia • improve glycaemic control • reduce weight in the obese • take regular exercise Number of risk factors Numberofdeathsper10,000patient-years Non-diabetic subjects Subjects with type 2 diabetes 0 1 2 3 0 20 40 60 80 100 120 140
107 Treatment of Cardiovascular Diseases Risk factors Hypertension SBP 130-139 or DPB 80-89 mmHg: lifestyle modification (DASH) for 3 months, if fails  pharmacological agents SBP ≥140 or DBP ≥90 mmHg: Lifestyle modification +pharmacological therapy Dyslipidemia Lifestyle modification + statins Antiplatelet agents* Aspirin and/or clopidogrel Smoking cessation Stop smoking, counseling CHD screening and treatment ACE-I and aspirin and statin (if not contraindicated) Diabetes Care 2012 *Depends on risk factors (???) Poor Control of CV Risk Factors in Diabetes (NHANES) Saydak SH et al. JAMA 2004 CV risk factors target Frequency • S-Cholesterol < 200 mg/dl (5.2 mmol/l) 52 % • BP < 130/80 mmHg 36 % • HbA1c < 7.0% 37 % • All three risk factors controlled 7 % • Unchanged CV risk factors from 1991 to 2000
108 STENO-2 STUDY The STENO2 Study – “a multifactorial approach to Type 2 Diabetes” New Engl J Med 2003; 383-93 New Engl J Med 2008; 358: 580-91 • 160 patients • Type 2 diabetes and microalbuminuria • Mean age 55 yrs, BMI 30 kg/m2; HbA1c 8.4 % • Randomized to • conventional therapy assigned to their GPs • or intensive care at Steno Diabetes Center
109 The STENO2 Study – Study Design Conventional treatment Intensive treatment Endpoint examinations Micro-vascular Macro-vascular 4 years 8 years 80 80 n=160 Advice to the Intensive Group • Food Advice • Cut down on animal fat • Have some kind of seafood every day • 5-6 vegetables and fruits every day • Exercise Advice • Enjoy physical performance > 150 min/week • Smoking cessation • Intensification of OHA and insulin • Treatment with ACE/ARB, Statin and baby aspirin
110 Patients in the Intensive Group had obtained better outcomes than patients in the Conventional Group… Intervention n=55 Standard n=38 Haemoglobin A1c (%) 7.7 8.0 F-s-total-cholesterol (mg/dl) 147 155 F-s-LDL-cholesterol (mg/dl) 71 77 F-s-triglycerides (mg/dl) 99 148 Systolic BP (mm Hg) 140 146 Diastolic BP (mm Hg) 74 73 Albumin excretion rate (mg/24h)* 69 75 Values are mean * median
111 The STENO2 Study Risk Reduction in Intensive Group Relative risk reduction after 8 years • Cardiovascular disease 53% • Diabetic Nephropathy 61% • Diabetic Retinopathy 58% • Autonomic Neuropathy 63% Screening, Treatment and Evaluation of Complications Lecture Main Learning PointsSummary • Complications should be screened for and treated according to guidelines • Routine follow up on treatment of complications should be performed • CVD complications are the mail cause of death among patients with diabetes • Risk of end-stage renal disease and blindness is significantly reduced by treatment of hyperglycemia and hypertension • Understand the treatment options for diabetes associated complications: • Nephropathy • Retinopathy • Neuropathy • Erectile Dysfunction • CVD • CAD
112 Assessment of Kidney function in Diabetes Mellitus type 2 GUIDELINES A.Annual Screening for albuminuria by : Albumin Excretion Rate (AER) – timed urine collection AER mg/ hour ug/min *in timed collection Microalbuminuria 30 - 300 20 - 200 Macroalbuminuria >300 >200 OR Albumin : Creatinine Ratio (ACR) – spot urine sample ACR Males (mg/mmol) Females (mg/mmol) Microalbuminuria 2,5 - 25 3,5 - 35 Macroalbuminuria >25 >35  If AER or ACR screening is positive for microalbuminuria : Perform additional ACR or AER measurements one to two times within 3 months. Microalbuminuria is confirmed if at least two or three tests (including the screening test) are positive.  If AER or ACR screening is positive for macroalbuminuria : Perform a 24 h urine collection for quantitation of protein excretion. AND B. Annual estimation of the Glomerular Filtration Rate (eGFR) eGFR Indicates <60 mL/min per 1,73 m2 At least moderate kidney dysfunction (stage 3 – 5 chronic kidney disease (CKD)) 60 – 90 mL/min per 1,73 m2 Mild kidney dysfunction (stage 2 CKD if albuminuria also present) Continue annual screening for albuminuria and eGFR in the event of negative screening tests. Reference : Chadban, et al. Nephrology 2010; 15, S146-S161
113 Simple Diabetes Foot Care Lecture: 30 minutes Simple Diabetes Foot Care Lecture Main Learning Points • Understand the risk factors for diabetic foot complications • Understand the steps for a simple diabetes foot examination • Understand the management of foot ulcers
114 From Theory to real-life – studies on foot care in RSCM 32% 26% 16% 26% RSCM 2003 Died Major Amputation and then Improved Discharge on their own will Improved without amputation 50% 14% 36% RSCM 2007 Died Amputation No Amputation Why foot care is important to diabetes management Have 15 – 40 fold higher risk of leg amputation than non diabetic Have a 15 % life time risk of developing foot ulcer Every 30 seconds a lower limb lost caused by diabetes 5-year suvival rate after major amputation < 50 % • 85% of diabetes-related amputations are happening in patients with foot ulcers • Early detection can prevent 40-85 % lower limb amputation Frykberg et al. J Foot Ankle Surg, 2000. IDF, International Working Group on Diabetic Foot 2007 Diabetes Patients
115 5 Cornerstones of diabetes foot care management Identification of risk factors Foot examination regularly Education (patients, providers and family) Treatment before Ulcer occurs Use appropriate footwear Risk Factors for diabetic foot ulceration Frykberg, Diabetic Microvascular Complications Today, May/June 2006 Intrinsic Factors Extrinsic Factors • Peripheral Neuropathy • Micro- and Macrovascular Diseases • Immunopahty • Structural Deformity • Limited Joint Mobility • Nephropathy • Age • Duration of Diabetes • Visual Acuity • Previous Ulceration • Minor mechanical trauma • Callus • Thermal Injury • Chemical Burns • Improper use of nail cutter • Smoking • Poor knowledge of diabetes • Psychological Factors • Alternative medication
116 Pathway to diabetic foot ulceration Reiber GE, Vileikyte, Boyko EJ et al. Causal pathways for incident lower–extremity ulcers in patients with from two settings. Diabetes Care 1999: 157-162 1% 30% 35%37% 63% 77%78% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Peripheral Neuropathy Peripheral Ischemia EdemaDeformityMinor Trauma Callus Infections Components leading to foot ulceration Intrinsic Factors Peripheral Neuropathy Autonomic SensoricMotoric Decreased Sweating Dry Skin Decreased Elasticity Fissure / Callus Ulcer • Loss of protective sensation • Decreased pain threshold • Lack of temperature sensation and proprioception Thermal Trauma in ‘bajaj’ Ill fitting Shoes
117 Intrinsic Factors Peripheral Arterial Disease (PAD) Risk Factors* • Hyperglycemia • Eleveted systolic blood pressure • hyperlipidemia • Smoking • Cardiovascular disease * UKPDS PAD • Correlated with atherosclerosis • A1c 1%  26 % PAD • More aggressive • Narrowing vessel lumen … obstructive • Distal tissue necrosis Intrinsic Factors Neuropathic Ulcers Influenced by: - Friction - Pressure
118 Intrinsic Factors Foot Deformities / Biomechanical Causes of Ulcers (Extrinsic Factors) Kyoto Foot Meeting 2010
119 Pathophysiology of diabetic foot Diabetes Mellitus Neuropathy Trauma Vascular Disease MOTOR Weakness Atrophy High Plantar Pressure Deformity Abnormal Stress Callus Formation Structural Deformity Cheiroarthropathy Impaired Response to Infection Diabetic Foot Ulcer AmputationAmputation AUTONOMIC Ischemia Diabetic Foot Disorders: A Clinical Practice Guideline (2006 Revision) SENSORY Loss of Protective Sensation Anhidrosis dry skin Sympathetic Tone MICROVASCULAR MACROVASCULAR Structural capillary BM thickening Functional AV Shunting Structural atherosclerosis Occlusive narrowing Ischemia Clinical Classification of diabetic foot (Edmond) Grade 1 Grade 2 Grade 3 Grade 4 Grade 5 Grade 6 Normal foot, no risk factors of neuropathy, ischemia, deformities No active ulcers, have ≥1 risk factors: neuropathy, ischemia, deformities, callus and swelling, nail deformities Skin breakdown; fisurre, blitser, ulcer Usually in plantar surface Foot develop infections, Discharge purulent, cellulitis, neuropathy and or ischemia Tissue necrosis with or with out intake foot, neuropathy, ischemia, neuroischemi, infection Unsalvageable foot, need major amputation, extensive necrosis, destroyed foot, severe infection
120 First 4 steps in the assessment Assessment Significant Finding Patient History - Previous foot ulceration - Previous amputation - Diabetic > 10 years - A1c > 7 % - Impaired vision - Neuropathic symptoms - Claudicatio Gross Inspection - Hammer toes - Claw toes - Halux valgus - Corn, callus, callus with ulcer, bunion - Prominent metatarsal head Dermatologic Examination - Dry skin - Absence of hair - Yellow or erythematous scale - Ulcer or healed ulcer - Interspace maceration - Moist - Unhealing ulceration Nail Deformities - Yellow, thickened nail - Ingrowing nail edge - Long or sharp nails 6 Steps for a complete Diabetes Foot Examination DIABETES FOOT EXAMINATION Patient History Gross Assess- ment Vascular Examination Screening for neuropathy Derma- tologic Examination Nail Defor- maties
121 Last 2 steps in the assessment Assessment Test Significant Finding Screening for Neuropathy - Semmes-Weinstein monofilamen 10 gram Lack of perception at one or more side - Tuning fork 128Hz Negative of vibration perception - Biothesiometer: Vibration perception Vibration perception threshold >25 volt Vascular Examination - Palpation of dorsalis pedis and tibialis posterior artery - Ankle Brachial Index - Color doppler • Decrease or absent pulse • ABI < 0.9 consistent with PAD ABI >1.2 0.9 – 1.2 <0.9 <0.6 Interpretation Rigid or calcified vessels or both Normal (or calcified) Ischemia Severe ischemia Risk Classification based on Foot Assessment Score Category Risk Profile Check-up Frequency 0 Low Risk • Pulsation ADP and ATP good • No deformities (hammer toe, claw toes, halux valgus, prominent metatarsal head) Once a year 1 Increased Risk • Pulsation ADP and ATP good • And/or deformities (hammer toe, claw toes, halux valgus, prominent metatarsal head) Once every 6 months 2 High Risk • ABI < 0,9 or ADP/ ATP not palpable • Deformities ( hammer toe, claw toes, halux valgus, , prominent metatarsal head Once every 3 months 3 Very High Risk • History of ulcer or amputation • Ulcer Once every 1-3 months
122 Intervention based on Risk Classification Score Category Intervention 0 Low Risk • Encourage extended knowledge on diabetes and foot care • Encourage self-care 1 Increased Risk • Inspect patient’s feet • Review need for vascular assessment • Evaluate footwear • Enhance foot care education 2 High Risk • Inspect patient's feet • Review need for vascular assessment • Evaluate provision and provide appropriate • Intensified foot care education • Specialist footwear and insoles • Skin and nail 3 Very High Risk • Multidisciplinary foot care team : • They should have unhindered access to suites for managing major wounds, • Urgent inpatient facilities • Antibiotic administration Prevention of Diabetes Foot DO Check your feet everyday Always wear footwear Check your footwear before wearing them Use shoes that fit Buy shoes in the afternoon Always use socks of cotton Wash your feet with soft soap and dry them Cut your nails in a flat way Check your feet regularly at the doctor Use lotion regularly at your skin DON’T’s Walk without shoes Use shoes that don’t fit Use socks that don’t fit to your foot Let your skin become dry Use sharp items to remove warts Smoke Use ring on finger Use high heels or shoes with sharp edges Over use of irritative lotion Use hot water to dip your feet
123 Wound Control1 1. Incision, drainage, debridement and necrotomy 2. Management of infections in tissue and bone 3. Exudate Management 4. Keep control of proliferation phase and infections Metabolic Control Infection Control Vascular Control Mechanic Control Wound Control Management of Foot Ulcers International Working Group on the Diabetic Foot 2007 1 2 3 4 5
124 Metabolic Control2 1. Hyperglycemia - Will inhibit process of wound recovery - Inhibit growth factor, collagen synthesis and fibroblast activities 2. Hypoalbuminemi 3. Hypertension 4. Decrease of heart and kidney function 5. Dyslipidemia 6. Anemia 7. Other diseases caused by diabetes Infection Control3 1. Need aggressive therapy 2. Usually there are no symptoms or signs of infection 3. External Infection: Positive gram bacteria 4. Internal Infection: Negative gram bacteria 5. Might need surgery
125 Use of Antibiotics3 Choice of antibiotics should be determined by: 1. Condition of the Infection: - Stage of infection and history of antibiotics - Bone infection, condition of blood vessels 2. Type of bacteria (sensitivity test) - Anarob, aerob, gram positive / gram negative 3. Condition of the patient - Allergy, heart and kidney function 4. Drug Profile - Safety, drug interactions, adverse events, frequency and dosage and price Vascular Control4 1. Neuroischemic Foot 2. Atherosclerosis can cause total block in the blood vessels 3. Decrease of blood flow to the wound 4. Critical Limb ischemia: Amputation Warning
126 Mechanic Control5 Principle: Reduce stress on the wound • Off loading • Might be bed rest • Non-weight bearing • Use of walker, wheel-chair or crutches • Use special shoes (‘half- shoes’) • Distribute the body weight to all surfaces of the foot Simple Diabetes Foot Care Lecture Main Learning PointsSummary • There are two risk factors for diabetic foot; intrinsic and extrinsic. • Check feet regularly to prevent ulcers. • Diabetes foot care management (Identification of risk factors, Foot examination regularly, treatment before ulcer occurs, use appropriate foot wear, education). • Management of foot ulcers (wound control, metabolic control, infection control, vascular control, mechanic control). • Understand the risk factors for diabetic foot complications • Understand the steps for a simple diabetes foot examination • Understand the management of foot ulcers
127 Slide1 First4stepsintheassessment AssessmentSignificantFinding Patient History -Previousfootulceration -Previousamputation -Diabetic>10years -A1c>7% -Impairedvision -Neuropaticsymptoms -Claudicatio Gross Inspection -Hammertoes -Clawtoes -Haluxvalgus -Corn,callus,calluswithulcer,bunion -Prominentmetatarsalhead Dermatologic Examination -Dryskin -Absenceofhair -Yelloworerythematousscale -Ulcerorhealedulcer -Interspacemaseration -Moist -Uhealingulceration Nail Deformaties -Yellow,thickenednail -Ingrowingnailedge -Longorsharpnails
128 Slide1 Last2stepsintheassessment AssessmentTestSignificantFinding Screeningfor Neuropathy -Semmes-Weinstein monofilamen10gram Lackofperseptionat oneormoreside -Tuningfork128HzNegativeofvibration perception -Biothesiometer: Vibrationperseption Vibrationperseption threshold>25volt Vascular Examination - Palpationofdorsalis pedisandtibialis posteriorarteri - AnkleBrachialIndex - Colordoppler ¥ Decreaseorabsent pulse ¥ ABI<0.9consistent withPAD ABI >1.2 0.9–1.2 <0.9 <0.6 Interpretation Rigidorcalcifiedvesselsorboth Normal(orcalcified) Ischaemia Severeischaemia
129 RiskClassificationbasedonFootAssessment ScoreCategoryRiskProfileCheck-up Frequency 0LowRisk •PulsationADPandATPgood •Nodeformities(hammertoe, clawtoes,haluxvalgus, prominentmethatarsalhead) Onceayear 1IncreasedRisk •PulsationADPandATPgood •And/ordeformities(hammertoe, clawtoes,haluxvalgus, prominentmethatarsalhead) Onceevery 6months 2HighRisk •ABI<0,9orADP/ATPnot palpable •Deformities(hammertoe,claw toes,haluxvalgus,,prominent methatarsalhead Onceevery 3months 3VeryHighRisk •Historyofulceroramputation •Ulcer Onceevery 1-3months
130 InterventionbasedonRiskClassification ScoreCategoryIntervention 0LowRisk •Encourageextendedknowledgeondiabetes andfootcare •Encourageself-care 1IncreasedRisk •Inspectpatient’sfeet •Reviewneedforvascularassessment •Evaluatefootwear •Enhancefootcareeducation 2HighRisk •Inspectpatient'sfeet •Reviewneedforvascularassessment •Evaluateprovisionandprovideappropriate •Intensifiedfootcareeducation •Specialistfootwearandinsoles •Skinandnail 3VeryHighRisk •Multidisciplinaryfootcareteam: •Theyshouldhaveunhinderedaccessto suitesformanagingmajorwounds, •Urgentinpatientfacilities •Antibioticadministration

Recomendados

Diabetes mellitus presentation
Diabetes mellitus presentationDiabetes mellitus presentation
Diabetes mellitus presentationlakshmi das
 
Chronic complications of diabetes mellitus
Chronic complications of diabetes mellitusChronic complications of diabetes mellitus
Chronic complications of diabetes mellitusHamza AlGhamdi
 
Diabetes mellitus
Diabetes mellitusDiabetes mellitus
Diabetes mellitusCarmela Domocmat
 
Diabetic nephropathy
Diabetic nephropathy Diabetic nephropathy
Diabetic nephropathy ahmad tanweer
 
Diabetes Mellitus
Diabetes MellitusDiabetes Mellitus
Diabetes Mellitusmigom doley
 
Diabetes mellitus
Diabetes mellitusDiabetes mellitus
Diabetes mellitusHope Inegbenosun
 
Diabetes mellitus
Diabetes mellitusDiabetes mellitus
Diabetes mellitusAbhra Ghosh
 
Diabetic Nephropathy Review
Diabetic Nephropathy ReviewDiabetic Nephropathy Review
Diabetic Nephropathy ReviewJAFAR ALSAID
 

Recomendados

Diabetes mellitus presentation
Diabetes mellitus presentationDiabetes mellitus presentation
Diabetes mellitus presentationlakshmi das
 
Chronic complications of diabetes mellitus
Chronic complications of diabetes mellitusChronic complications of diabetes mellitus
Chronic complications of diabetes mellitusHamza AlGhamdi
 
Diabetes mellitus
Diabetes mellitusDiabetes mellitus
Diabetes mellitusCarmela Domocmat
 
Diabetic nephropathy
Diabetic nephropathy Diabetic nephropathy
Diabetic nephropathy ahmad tanweer
 
Diabetes Mellitus
Diabetes MellitusDiabetes Mellitus
Diabetes Mellitusmigom doley
 
Diabetes mellitus
Diabetes mellitusDiabetes mellitus
Diabetes mellitusHope Inegbenosun
 
Diabetes mellitus
Diabetes mellitusDiabetes mellitus
Diabetes mellitusAbhra Ghosh
 
Diabetic Nephropathy Review
Diabetic Nephropathy ReviewDiabetic Nephropathy Review
Diabetic Nephropathy ReviewJAFAR ALSAID
 
Diabetic nephropathy
Diabetic nephropathyDiabetic nephropathy
Diabetic nephropathyAnkur Varshney
 
Diabetes mellitus
Diabetes mellitusDiabetes mellitus
Diabetes mellitusMd Jahirul Islam Sojib
 
Diabetes
DiabetesDiabetes
DiabetesPoonam Singh
 
Management of Diabetes.pptx
Management of Diabetes.pptxManagement of Diabetes.pptx
Management of Diabetes.pptxOriba Dan Langoya
 
Diabetes
DiabetesDiabetes
DiabetesDr. Somak Majumdar
 
Diabetes
Diabetes Diabetes
Diabetes Balaji Thorat
 
Type 2 diabetes
Type 2 diabetesType 2 diabetes
Type 2 diabetesCarlosKid14
 
CME Sohag | internal medicine | Diabetes mellitus
CME Sohag | internal medicine | Diabetes mellitusCME Sohag | internal medicine | Diabetes mellitus
CME Sohag | internal medicine | Diabetes mellitusEmad Qasem
 
Diabetes mellitus
Diabetes mellitusDiabetes mellitus
Diabetes mellitusAlmuataz Bellah Ahmad
 
...DIAGNOSIS OF DIABETES MELLITUS...
...DIAGNOSIS OF DIABETES MELLITUS......DIAGNOSIS OF DIABETES MELLITUS...
...DIAGNOSIS OF DIABETES MELLITUS...Dr.Subir Kumar
 
DIABETES MELLITUS an up-to-date 2017- 2018
DIABETES MELLITUS an up-to-date 2017- 2018DIABETES MELLITUS an up-to-date 2017- 2018
DIABETES MELLITUS an up-to-date 2017- 2018Md. Zahirul Islam
 
Mody vs type 1&type 2
Mody vs type 1&type 2Mody vs type 1&type 2
Mody vs type 1&type 2Abdulmoein AlAgha
 
Diabetes mellitus
Diabetes mellitus Diabetes mellitus
Diabetes mellitus Murtadha Adil
 
Diabetic kidney disease 2021
Diabetic kidney disease 2021Diabetic kidney disease 2021
Diabetic kidney disease 2021Christos Argyropoulos
 
Ppt presentation on diabetes mellitus
Ppt presentation on diabetes mellitusPpt presentation on diabetes mellitus
Ppt presentation on diabetes mellitusDrSangeetaBhujbal
 
Diabetic nephropathy, patho physiology update
Diabetic nephropathy, patho physiology updateDiabetic nephropathy, patho physiology update
Diabetic nephropathy, patho physiology updateأحمد عبد الوهاب الجندي
 
Tight Glycemic Control in the Prevention of Cardiovascular Disease
Tight Glycemic Control in the Prevention of Cardiovascular DiseaseTight Glycemic Control in the Prevention of Cardiovascular Disease
Tight Glycemic Control in the Prevention of Cardiovascular DiseaseIris Thiele Isip-Tan
 
Diabetes
DiabetesDiabetes
DiabetesAssociate professor
 
Diabetes
DiabetesDiabetes
DiabetesFatima AlSaadi
 
Diagnosis of diabetes mellitus
Diagnosis of diabetes mellitus Diagnosis of diabetes mellitus
Diagnosis of diabetes mellitus Dilek Gogas Yavuz
 
Diabetes powerpoint
Diabetes powerpointDiabetes powerpoint
Diabetes powerpointmldanforth
 
Manajemen waktu dalam aktivitas sekretaris dan pengelolaan agenda
Manajemen waktu dalam aktivitas sekretaris dan pengelolaan agendaManajemen waktu dalam aktivitas sekretaris dan pengelolaan agenda
Manajemen waktu dalam aktivitas sekretaris dan pengelolaan agendaRhiechy Yogatama
 

Más contenido relacionado

La actualidad más candente

CME Sohag | internal medicine | Diabetes mellitus
CME Sohag | internal medicine | Diabetes mellitusCME Sohag | internal medicine | Diabetes mellitus
CME Sohag | internal medicine | Diabetes mellitusEmad Qasem
 
...DIAGNOSIS OF DIABETES MELLITUS...
...DIAGNOSIS OF DIABETES MELLITUS......DIAGNOSIS OF DIABETES MELLITUS...
...DIAGNOSIS OF DIABETES MELLITUS...Dr.Subir Kumar
 
DIABETES MELLITUS an up-to-date 2017- 2018
DIABETES MELLITUS an up-to-date 2017- 2018DIABETES MELLITUS an up-to-date 2017- 2018
DIABETES MELLITUS an up-to-date 2017- 2018Md. Zahirul Islam
 
Ppt presentation on diabetes mellitus
Ppt presentation on diabetes mellitusPpt presentation on diabetes mellitus
Ppt presentation on diabetes mellitusDrSangeetaBhujbal
 
Tight Glycemic Control in the Prevention of Cardiovascular Disease
Tight Glycemic Control in the Prevention of Cardiovascular DiseaseTight Glycemic Control in the Prevention of Cardiovascular Disease
Tight Glycemic Control in the Prevention of Cardiovascular DiseaseIris Thiele Isip-Tan
 
Diagnosis of diabetes mellitus
Diagnosis of diabetes mellitus Diagnosis of diabetes mellitus
Diagnosis of diabetes mellitus Dilek Gogas Yavuz
 

La actualidad más candente (20)

Diabetic nephropathy
Diabetic nephropathyDiabetic nephropathy
Diabetic nephropathy
 
Diabetes mellitus
Diabetes mellitusDiabetes mellitus
Diabetes mellitus
 
Diabetes
DiabetesDiabetes
Diabetes
 
Management of Diabetes.pptx
Management of Diabetes.pptxManagement of Diabetes.pptx
Management of Diabetes.pptx
 
Diabetes
DiabetesDiabetes
Diabetes
 
Diabetes
Diabetes Diabetes
Diabetes
 
Type 2 diabetes
Type 2 diabetesType 2 diabetes
Type 2 diabetes
 
CME Sohag | internal medicine | Diabetes mellitus
CME Sohag | internal medicine | Diabetes mellitusCME Sohag | internal medicine | Diabetes mellitus
CME Sohag | internal medicine | Diabetes mellitus
 
Diabetes mellitus
Diabetes mellitusDiabetes mellitus
Diabetes mellitus
 
...DIAGNOSIS OF DIABETES MELLITUS...
...DIAGNOSIS OF DIABETES MELLITUS......DIAGNOSIS OF DIABETES MELLITUS...
...DIAGNOSIS OF DIABETES MELLITUS...
 
DIABETES MELLITUS an up-to-date 2017- 2018
DIABETES MELLITUS an up-to-date 2017- 2018DIABETES MELLITUS an up-to-date 2017- 2018
DIABETES MELLITUS an up-to-date 2017- 2018
 
Mody vs type 1&type 2
Mody vs type 1&type 2Mody vs type 1&type 2
Mody vs type 1&type 2
 
Diabetes mellitus
Diabetes mellitus Diabetes mellitus
Diabetes mellitus
 
Diabetic kidney disease 2021
Diabetic kidney disease 2021Diabetic kidney disease 2021
Diabetic kidney disease 2021
 
Ppt presentation on diabetes mellitus
Ppt presentation on diabetes mellitusPpt presentation on diabetes mellitus
Ppt presentation on diabetes mellitus
 
Diabetic nephropathy, patho physiology update
Diabetic nephropathy, patho physiology updateDiabetic nephropathy, patho physiology update
Diabetic nephropathy, patho physiology update
 
Tight Glycemic Control in the Prevention of Cardiovascular Disease
Tight Glycemic Control in the Prevention of Cardiovascular DiseaseTight Glycemic Control in the Prevention of Cardiovascular Disease
Tight Glycemic Control in the Prevention of Cardiovascular Disease
 
Diabetes
DiabetesDiabetes
Diabetes
 
Diabetes
DiabetesDiabetes
Diabetes
 
Diagnosis of diabetes mellitus
Diagnosis of diabetes mellitus Diagnosis of diabetes mellitus
Diagnosis of diabetes mellitus
 

Destacado

Diabetes powerpoint
Diabetes powerpointDiabetes powerpoint
Diabetes powerpointmldanforth
 
Manajemen waktu dalam aktivitas sekretaris dan pengelolaan agenda
Manajemen waktu dalam aktivitas sekretaris dan pengelolaan agendaManajemen waktu dalam aktivitas sekretaris dan pengelolaan agenda
Manajemen waktu dalam aktivitas sekretaris dan pengelolaan agendaRhiechy Yogatama
 
Mengenal Diabetes Mellitus
Mengenal Diabetes MellitusMengenal Diabetes Mellitus
Mengenal Diabetes Mellitusjasmine2688
 

Destacado (7)

Diabetes powerpoint
Diabetes powerpointDiabetes powerpoint
Diabetes powerpoint
 
Manajemen waktu dalam aktivitas sekretaris dan pengelolaan agenda
Manajemen waktu dalam aktivitas sekretaris dan pengelolaan agendaManajemen waktu dalam aktivitas sekretaris dan pengelolaan agenda
Manajemen waktu dalam aktivitas sekretaris dan pengelolaan agenda
 
TB Paru
TB ParuTB Paru
TB Paru
 
Tuberkulosis penyuluhan
Tuberkulosis penyuluhanTuberkulosis penyuluhan
Tuberkulosis penyuluhan
 
POWERPOINT TB PARU
POWERPOINT TB PARUPOWERPOINT TB PARU
POWERPOINT TB PARU
 
Mengenal Diabetes Mellitus
Mengenal Diabetes MellitusMengenal Diabetes Mellitus
Mengenal Diabetes Mellitus
 
GESTATIONAL DIABETES
GESTATIONAL DIABETESGESTATIONAL DIABETES
GESTATIONAL DIABETES
 

Similar a Materi Workshop Diabetes Melitus untuk Dokter Umum - Practical Management of Diabetes and Its Complication for General Practitioner

Ueda2015 gdm dr.lobna el-toony
Ueda2015 gdm dr.lobna el-toonyUeda2015 gdm dr.lobna el-toony
Ueda2015 gdm dr.lobna el-toonyueda2015
 
Risk factors for diabetes during childhood
Risk factors for diabetes during childhoodRisk factors for diabetes during childhood
Risk factors for diabetes during childhoodPratyush1693
 
T1D-S4-Treatment.051217.pdf
T1D-S4-Treatment.051217.pdfT1D-S4-Treatment.051217.pdf
T1D-S4-Treatment.051217.pdfAliEllaffi
 
Ueda 2016 2-pathophysiology ,classification &amp; diagnosis of diabetes - kha...
Ueda 2016 2-pathophysiology ,classification &amp; diagnosis of diabetes - kha...Ueda 2016 2-pathophysiology ,classification &amp; diagnosis of diabetes - kha...
Ueda 2016 2-pathophysiology ,classification &amp; diagnosis of diabetes - kha...ueda2015
 
EPIDEMIOLOGY OF DIABETES.pptx
EPIDEMIOLOGY OF DIABETES.pptxEPIDEMIOLOGY OF DIABETES.pptx
EPIDEMIOLOGY OF DIABETES.pptxSteve462
 
EB 2016 - 4th Yogurt Summit - Constance Brown-Riggs
EB 2016 - 4th Yogurt Summit - Constance Brown-RiggsEB 2016 - 4th Yogurt Summit - Constance Brown-Riggs
EB 2016 - 4th Yogurt Summit - Constance Brown-RiggsYogurt in Nutrition #YINI
 
Biology project
Biology projectBiology project
Biology projectHarsh Jain
 
what diabetes is?.pdf
what diabetes is?.pdfwhat diabetes is?.pdf
what diabetes is?.pdffawzi morsy
 
Insulin Presentation-Gulu.pptx
Insulin Presentation-Gulu.pptxInsulin Presentation-Gulu.pptx
Insulin Presentation-Gulu.pptxDeriqueJoshua2
 
SGLT2 inhibitor -A boon in uncontrolled dm
SGLT2 inhibitor -A boon in uncontrolled dmSGLT2 inhibitor -A boon in uncontrolled dm
SGLT2 inhibitor -A boon in uncontrolled dmdr nirmal jaiswal
 
Know the signs and symptoms of diabetes and possible solutions
Know the signs and symptoms of diabetes and possible solutionsKnow the signs and symptoms of diabetes and possible solutions
Know the signs and symptoms of diabetes and possible solutionssupreme100
 
Beyond metformin dr clayton feb 22
Beyond metformin dr clayton feb 22Beyond metformin dr clayton feb 22
Beyond metformin dr clayton feb 22Ihsaan Peer
 
What Spine Surgeons Need to Know About Dietary Strategies for Heart Disease a...
What Spine Surgeons Need to Know About Dietary Strategies for Heart Disease a...What Spine Surgeons Need to Know About Dietary Strategies for Heart Disease a...
What Spine Surgeons Need to Know About Dietary Strategies for Heart Disease a...James McCarter
 
Impact of patient counseling on diabetes mellitus patients in the territory c...
Impact of patient counseling on diabetes mellitus patients in the territory c...Impact of patient counseling on diabetes mellitus patients in the territory c...
Impact of patient counseling on diabetes mellitus patients in the territory c...SriramNagarajan17
 

Similar a Materi Workshop Diabetes Melitus untuk Dokter Umum - Practical Management of Diabetes and Its Complication for General Practitioner (20)

Prediabetes a new appraisal
Prediabetes a new appraisal Prediabetes a new appraisal
Prediabetes a new appraisal
 
Resiko metabolik
Resiko metabolik Resiko metabolik
Resiko metabolik
 
Ueda2015 gdm dr.lobna el-toony
Ueda2015 gdm dr.lobna el-toonyUeda2015 gdm dr.lobna el-toony
Ueda2015 gdm dr.lobna el-toony
 
Risk factors for diabetes during childhood
Risk factors for diabetes during childhoodRisk factors for diabetes during childhood
Risk factors for diabetes during childhood
 
T1D-S4-Treatment.051217.pdf
T1D-S4-Treatment.051217.pdfT1D-S4-Treatment.051217.pdf
T1D-S4-Treatment.051217.pdf
 
Ueda 2016 2-pathophysiology ,classification &amp; diagnosis of diabetes - kha...
Ueda 2016 2-pathophysiology ,classification &amp; diagnosis of diabetes - kha...Ueda 2016 2-pathophysiology ,classification &amp; diagnosis of diabetes - kha...
Ueda 2016 2-pathophysiology ,classification &amp; diagnosis of diabetes - kha...
 
EPIDEMIOLOGY OF DIABETES.pptx
EPIDEMIOLOGY OF DIABETES.pptxEPIDEMIOLOGY OF DIABETES.pptx
EPIDEMIOLOGY OF DIABETES.pptx
 
EB 2016 - 4th Yogurt Summit - Constance Brown-Riggs
EB 2016 - 4th Yogurt Summit - Constance Brown-RiggsEB 2016 - 4th Yogurt Summit - Constance Brown-Riggs
EB 2016 - 4th Yogurt Summit - Constance Brown-Riggs
 
Managing Type 2 Diabetes
Managing Type 2 DiabetesManaging Type 2 Diabetes
Managing Type 2 Diabetes
 
Biology project
Biology projectBiology project
Biology project
 
what diabetes is?.pdf
what diabetes is?.pdfwhat diabetes is?.pdf
what diabetes is?.pdf
 
Insulin Presentation-Gulu.pptx
Insulin Presentation-Gulu.pptxInsulin Presentation-Gulu.pptx
Insulin Presentation-Gulu.pptx
 
DM IN PREGN.pdf
DM IN PREGN.pdfDM IN PREGN.pdf
DM IN PREGN.pdf
 
J044080093
J044080093J044080093
J044080093
 
Glp1 clinical view
Glp1 clinical viewGlp1 clinical view
Glp1 clinical view
 
SGLT2 inhibitor -A boon in uncontrolled dm
SGLT2 inhibitor -A boon in uncontrolled dmSGLT2 inhibitor -A boon in uncontrolled dm
SGLT2 inhibitor -A boon in uncontrolled dm
 
Know the signs and symptoms of diabetes and possible solutions
Know the signs and symptoms of diabetes and possible solutionsKnow the signs and symptoms of diabetes and possible solutions
Know the signs and symptoms of diabetes and possible solutions
 
Beyond metformin dr clayton feb 22
Beyond metformin dr clayton feb 22Beyond metformin dr clayton feb 22
Beyond metformin dr clayton feb 22
 
What Spine Surgeons Need to Know About Dietary Strategies for Heart Disease a...
What Spine Surgeons Need to Know About Dietary Strategies for Heart Disease a...What Spine Surgeons Need to Know About Dietary Strategies for Heart Disease a...
What Spine Surgeons Need to Know About Dietary Strategies for Heart Disease a...
 
Impact of patient counseling on diabetes mellitus patients in the territory c...
Impact of patient counseling on diabetes mellitus patients in the territory c...Impact of patient counseling on diabetes mellitus patients in the territory c...
Impact of patient counseling on diabetes mellitus patients in the territory c...
 

Más de Dayu Agung Dewi Sawitri

Materi Seminar HKN ke 50 : Obesitas dan Infertilitas
Materi Seminar HKN ke 50 : Obesitas dan Infertilitas Materi Seminar HKN ke 50 : Obesitas dan Infertilitas
Materi Seminar HKN ke 50 : Obesitas dan Infertilitas Dayu Agung Dewi Sawitri
 
Panduan Praktik Klinis Bagi Dokter Di Fasilitas Pelayanan Kesehatan Primer
Panduan Praktik Klinis Bagi Dokter Di Fasilitas Pelayanan Kesehatan Primer Panduan Praktik Klinis Bagi Dokter Di Fasilitas Pelayanan Kesehatan Primer
Panduan Praktik Klinis Bagi Dokter Di Fasilitas Pelayanan Kesehatan Primer Dayu Agung Dewi Sawitri
 
Materi Pelatihan PONED - Asfiksia dan Resusitasi Bayi Baru Lahir
Materi Pelatihan PONED - Asfiksia dan Resusitasi Bayi Baru LahirMateri Pelatihan PONED - Asfiksia dan Resusitasi Bayi Baru Lahir
Materi Pelatihan PONED - Asfiksia dan Resusitasi Bayi Baru LahirDayu Agung Dewi Sawitri
 
Pedoman Nasional Pelayanan Kedokteran Tata Laksana Tuberkulosis - 2013
Pedoman Nasional Pelayanan Kedokteran Tata Laksana Tuberkulosis - 2013Pedoman Nasional Pelayanan Kedokteran Tata Laksana Tuberkulosis - 2013
Pedoman Nasional Pelayanan Kedokteran Tata Laksana Tuberkulosis - 2013Dayu Agung Dewi Sawitri
 
PENGENALAN KELAS IBU HAMIL DI UPT. KESMAS TAMPAKSIRING II
PENGENALAN KELAS IBU HAMIL DI UPT. KESMAS TAMPAKSIRING IIPENGENALAN KELAS IBU HAMIL DI UPT. KESMAS TAMPAKSIRING II
PENGENALAN KELAS IBU HAMIL DI UPT. KESMAS TAMPAKSIRING IIDayu Agung Dewi Sawitri
 
KEBIJAKAN PROGRAM KESEHATAN IBU DAN ANAK OLEH DINAS KESEHATAN KABUPATEN GIANYAR
KEBIJAKAN PROGRAM KESEHATAN IBU DAN ANAK OLEH DINAS KESEHATAN KABUPATEN GIANYARKEBIJAKAN PROGRAM KESEHATAN IBU DAN ANAK OLEH DINAS KESEHATAN KABUPATEN GIANYAR
KEBIJAKAN PROGRAM KESEHATAN IBU DAN ANAK OLEH DINAS KESEHATAN KABUPATEN GIANYARDayu Agung Dewi Sawitri
 
MATERI PENYULUHAN PHBS (PERILAKU HIDUP BERSIH DAN SEHAT) DI SEKOLAH DASAR
MATERI PENYULUHAN PHBS (PERILAKU HIDUP BERSIH DAN SEHAT) DI SEKOLAH DASAR MATERI PENYULUHAN PHBS (PERILAKU HIDUP BERSIH DAN SEHAT) DI SEKOLAH DASAR
MATERI PENYULUHAN PHBS (PERILAKU HIDUP BERSIH DAN SEHAT) DI SEKOLAH DASAR Dayu Agung Dewi Sawitri
 
PENGENALAN MATERI SPIP (SISTEM PENGENDALIAN INTERN PEMERINTAH) DI UPT. KESMAS...
PENGENALAN MATERI SPIP (SISTEM PENGENDALIAN INTERN PEMERINTAH) DI UPT. KESMAS...PENGENALAN MATERI SPIP (SISTEM PENGENDALIAN INTERN PEMERINTAH) DI UPT. KESMAS...
PENGENALAN MATERI SPIP (SISTEM PENGENDALIAN INTERN PEMERINTAH) DI UPT. KESMAS...Dayu Agung Dewi Sawitri
 
PENERAPAN PROGRAM PERKESMAS DI UPT KESMAS TAMPAKSIRING II GIANYAR - BALI TAHU...
PENERAPAN PROGRAM PERKESMAS DI UPT KESMAS TAMPAKSIRING II GIANYAR - BALI TAHU...PENERAPAN PROGRAM PERKESMAS DI UPT KESMAS TAMPAKSIRING II GIANYAR - BALI TAHU...
PENERAPAN PROGRAM PERKESMAS DI UPT KESMAS TAMPAKSIRING II GIANYAR - BALI TAHU...Dayu Agung Dewi Sawitri
 
IMPLEMENTASI FORMULARIUM NASIONAL DALAM PELAKSANAAN PELAYANAN KESEHATAN
IMPLEMENTASI FORMULARIUM NASIONAL DALAM PELAKSANAAN PELAYANAN KESEHATAN IMPLEMENTASI FORMULARIUM NASIONAL DALAM PELAKSANAAN PELAYANAN KESEHATAN
IMPLEMENTASI FORMULARIUM NASIONAL DALAM PELAKSANAAN PELAYANAN KESEHATAN Dayu Agung Dewi Sawitri
 
Materi Pembinaan Kader Kesehatan Remaja (KKR) - KESPRO
Materi Pembinaan Kader Kesehatan Remaja (KKR) - KESPROMateri Pembinaan Kader Kesehatan Remaja (KKR) - KESPRO
Materi Pembinaan Kader Kesehatan Remaja (KKR) - KESPRODayu Agung Dewi Sawitri
 
PROFIL UPT. KESMAS TAMPAKSIRING II GIANYAR - BALI
PROFIL UPT. KESMAS TAMPAKSIRING II GIANYAR - BALIPROFIL UPT. KESMAS TAMPAKSIRING II GIANYAR - BALI
PROFIL UPT. KESMAS TAMPAKSIRING II GIANYAR - BALIDayu Agung Dewi Sawitri
 

Más de Dayu Agung Dewi Sawitri (15)

Materi Seminar HKN ke 50 : Obesitas dan Infertilitas
Materi Seminar HKN ke 50 : Obesitas dan Infertilitas Materi Seminar HKN ke 50 : Obesitas dan Infertilitas
Materi Seminar HKN ke 50 : Obesitas dan Infertilitas
 
Panduan Praktik Klinis Bagi Dokter Di Fasilitas Pelayanan Kesehatan Primer
Panduan Praktik Klinis Bagi Dokter Di Fasilitas Pelayanan Kesehatan Primer Panduan Praktik Klinis Bagi Dokter Di Fasilitas Pelayanan Kesehatan Primer
Panduan Praktik Klinis Bagi Dokter Di Fasilitas Pelayanan Kesehatan Primer
 
Standar Kompetensi Dokter Indonesia
Standar Kompetensi Dokter IndonesiaStandar Kompetensi Dokter Indonesia
Standar Kompetensi Dokter Indonesia
 
Materi Pelatihan PONED - Asfiksia dan Resusitasi Bayi Baru Lahir
Materi Pelatihan PONED - Asfiksia dan Resusitasi Bayi Baru LahirMateri Pelatihan PONED - Asfiksia dan Resusitasi Bayi Baru Lahir
Materi Pelatihan PONED - Asfiksia dan Resusitasi Bayi Baru Lahir
 
Pedoman Nasional Pelayanan Kedokteran Tata Laksana Tuberkulosis - 2013
Pedoman Nasional Pelayanan Kedokteran Tata Laksana Tuberkulosis - 2013Pedoman Nasional Pelayanan Kedokteran Tata Laksana Tuberkulosis - 2013
Pedoman Nasional Pelayanan Kedokteran Tata Laksana Tuberkulosis - 2013
 
PENGENALAN KELAS IBU HAMIL DI UPT. KESMAS TAMPAKSIRING II
PENGENALAN KELAS IBU HAMIL DI UPT. KESMAS TAMPAKSIRING IIPENGENALAN KELAS IBU HAMIL DI UPT. KESMAS TAMPAKSIRING II
PENGENALAN KELAS IBU HAMIL DI UPT. KESMAS TAMPAKSIRING II
 
KEBIJAKAN PROGRAM KESEHATAN IBU DAN ANAK OLEH DINAS KESEHATAN KABUPATEN GIANYAR
KEBIJAKAN PROGRAM KESEHATAN IBU DAN ANAK OLEH DINAS KESEHATAN KABUPATEN GIANYARKEBIJAKAN PROGRAM KESEHATAN IBU DAN ANAK OLEH DINAS KESEHATAN KABUPATEN GIANYAR
KEBIJAKAN PROGRAM KESEHATAN IBU DAN ANAK OLEH DINAS KESEHATAN KABUPATEN GIANYAR
 
MATERI PENYULUHAN PHBS (PERILAKU HIDUP BERSIH DAN SEHAT) DI SEKOLAH DASAR
MATERI PENYULUHAN PHBS (PERILAKU HIDUP BERSIH DAN SEHAT) DI SEKOLAH DASAR MATERI PENYULUHAN PHBS (PERILAKU HIDUP BERSIH DAN SEHAT) DI SEKOLAH DASAR
MATERI PENYULUHAN PHBS (PERILAKU HIDUP BERSIH DAN SEHAT) DI SEKOLAH DASAR
 
PENGENALAN MATERI SPIP (SISTEM PENGENDALIAN INTERN PEMERINTAH) DI UPT. KESMAS...
PENGENALAN MATERI SPIP (SISTEM PENGENDALIAN INTERN PEMERINTAH) DI UPT. KESMAS...PENGENALAN MATERI SPIP (SISTEM PENGENDALIAN INTERN PEMERINTAH) DI UPT. KESMAS...
PENGENALAN MATERI SPIP (SISTEM PENGENDALIAN INTERN PEMERINTAH) DI UPT. KESMAS...
 
PENERAPAN PROGRAM PERKESMAS DI UPT KESMAS TAMPAKSIRING II GIANYAR - BALI TAHU...
PENERAPAN PROGRAM PERKESMAS DI UPT KESMAS TAMPAKSIRING II GIANYAR - BALI TAHU...PENERAPAN PROGRAM PERKESMAS DI UPT KESMAS TAMPAKSIRING II GIANYAR - BALI TAHU...
PENERAPAN PROGRAM PERKESMAS DI UPT KESMAS TAMPAKSIRING II GIANYAR - BALI TAHU...
 
IMPLEMENTASI FORMULARIUM NASIONAL DALAM PELAKSANAAN PELAYANAN KESEHATAN
IMPLEMENTASI FORMULARIUM NASIONAL DALAM PELAKSANAAN PELAYANAN KESEHATAN IMPLEMENTASI FORMULARIUM NASIONAL DALAM PELAKSANAAN PELAYANAN KESEHATAN
IMPLEMENTASI FORMULARIUM NASIONAL DALAM PELAKSANAAN PELAYANAN KESEHATAN
 
Materi Pembinaan Kader Kesehatan Remaja (KKR) - KESPRO
Materi Pembinaan Kader Kesehatan Remaja (KKR) - KESPROMateri Pembinaan Kader Kesehatan Remaja (KKR) - KESPRO
Materi Pembinaan Kader Kesehatan Remaja (KKR) - KESPRO
 
PROFIL UPT. KESMAS TAMPAKSIRING II GIANYAR - BALI
PROFIL UPT. KESMAS TAMPAKSIRING II GIANYAR - BALIPROFIL UPT. KESMAS TAMPAKSIRING II GIANYAR - BALI
PROFIL UPT. KESMAS TAMPAKSIRING II GIANYAR - BALI
 
Koordinasi JKN di Kabupaten Gianyar
Koordinasi JKN di Kabupaten GianyarKoordinasi JKN di Kabupaten Gianyar
Koordinasi JKN di Kabupaten Gianyar
 
Icd 10 2nd-ed_volume2
Icd 10 2nd-ed_volume2Icd 10 2nd-ed_volume2
Icd 10 2nd-ed_volume2
 

Último

VIP Hyderabad Call Girls Bahadurpally 7877925207 ₹5000 To 25K With AC Room 💚😋
VIP Hyderabad Call Girls Bahadurpally 7877925207 ₹5000 To 25K With AC Room 💚😋VIP Hyderabad Call Girls Bahadurpally 7877925207 ₹5000 To 25K With AC Room 💚😋
VIP Hyderabad Call Girls Bahadurpally 7877925207 ₹5000 To 25K With AC Room 💚😋TANUJA PANDEY
 
Premium Call Girls Cottonpet Whatsapp 7001035870 Independent Escort Service
Premium Call Girls Cottonpet Whatsapp 7001035870 Independent Escort ServicePremium Call Girls Cottonpet Whatsapp 7001035870 Independent Escort Service
Premium Call Girls Cottonpet Whatsapp 7001035870 Independent Escort Servicevidya singh
 
Top Rated Bangalore Call Girls Richmond Circle ⟟ 8250192130 ⟟ Call Me For Gen...
Top Rated Bangalore Call Girls Richmond Circle ⟟ 8250192130 ⟟ Call Me For Gen...Top Rated Bangalore Call Girls Richmond Circle ⟟ 8250192130 ⟟ Call Me For Gen...
Top Rated Bangalore Call Girls Richmond Circle ⟟ 8250192130 ⟟ Call Me For Gen...narwatsonia7
 
College Call Girls in Haridwar 9667172968 Short 4000 Night 10000 Best call gi...
College Call Girls in Haridwar 9667172968 Short 4000 Night 10000 Best call gi...College Call Girls in Haridwar 9667172968 Short 4000 Night 10000 Best call gi...
College Call Girls in Haridwar 9667172968 Short 4000 Night 10000 Best call gi...perfect solution
 
(Rocky) Jaipur Call Girl - 09521753030 Escorts Service 50% Off with Cash ON D...
(Rocky) Jaipur Call Girl - 09521753030 Escorts Service 50% Off with Cash ON D...(Rocky) Jaipur Call Girl - 09521753030 Escorts Service 50% Off with Cash ON D...
(Rocky) Jaipur Call Girl - 09521753030 Escorts Service 50% Off with Cash ON D...indiancallgirl4rent
 
Night 7k to 12k Navi Mumbai Call Girl Photo 👉 BOOK NOW 9833363713 👈 ♀️ night ...
Night 7k to 12k Navi Mumbai Call Girl Photo 👉 BOOK NOW 9833363713 👈 ♀️ night ...Night 7k to 12k Navi Mumbai Call Girl Photo 👉 BOOK NOW 9833363713 👈 ♀️ night ...
Night 7k to 12k Navi Mumbai Call Girl Photo 👉 BOOK NOW 9833363713 👈 ♀️ night ...aartirawatdelhi
 
Call Girls Service Jaipur Grishma WhatsApp ❤8445551418 VIP Call Girls Jaipur
Call Girls Service Jaipur Grishma WhatsApp ❤8445551418 VIP Call Girls JaipurCall Girls Service Jaipur Grishma WhatsApp ❤8445551418 VIP Call Girls Jaipur
Call Girls Service Jaipur Grishma WhatsApp ❤8445551418 VIP Call Girls Jaipurparulsinha
 
Call Girls Mumbai Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Mumbai Just Call 9907093804 Top Class Call Girl Service AvailableCall Girls Mumbai Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Mumbai Just Call 9907093804 Top Class Call Girl Service AvailableDipal Arora
 
Call Girls Faridabad Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Faridabad Just Call 9907093804 Top Class Call Girl Service AvailableCall Girls Faridabad Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Faridabad Just Call 9907093804 Top Class Call Girl Service AvailableDipal Arora
 
Russian Call Girls in Jaipur Riya WhatsApp ❤8445551418 VIP Call Girls Jaipur
Russian Call Girls in Jaipur Riya WhatsApp ❤8445551418 VIP Call Girls JaipurRussian Call Girls in Jaipur Riya WhatsApp ❤8445551418 VIP Call Girls Jaipur
Russian Call Girls in Jaipur Riya WhatsApp ❤8445551418 VIP Call Girls Jaipurparulsinha
 
Call Girls Kochi Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Kochi Just Call 9907093804 Top Class Call Girl Service AvailableCall Girls Kochi Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Kochi Just Call 9907093804 Top Class Call Girl Service AvailableDipal Arora
 
Call Girls Jabalpur Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Jabalpur Just Call 9907093804 Top Class Call Girl Service AvailableCall Girls Jabalpur Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Jabalpur Just Call 9907093804 Top Class Call Girl Service AvailableDipal Arora
 
VIP Call Girls Indore Kirti 💚😋 9256729539 🚀 Indore Escorts
VIP Call Girls Indore Kirti 💚😋 9256729539 🚀 Indore EscortsVIP Call Girls Indore Kirti 💚😋 9256729539 🚀 Indore Escorts
VIP Call Girls Indore Kirti 💚😋 9256729539 🚀 Indore Escortsaditipandeya
 
VIP Service Call Girls Sindhi Colony 📳 7877925207 For 18+ VIP Call Girl At Th...
VIP Service Call Girls Sindhi Colony 📳 7877925207 For 18+ VIP Call Girl At Th...VIP Service Call Girls Sindhi Colony 📳 7877925207 For 18+ VIP Call Girl At Th...
VIP Service Call Girls Sindhi Colony 📳 7877925207 For 18+ VIP Call Girl At Th...jageshsingh5554
 
Night 7k to 12k Chennai City Center Call Girls 👉👉 7427069034⭐⭐ 100% Genuine E...
Night 7k to 12k Chennai City Center Call Girls 👉👉 7427069034⭐⭐ 100% Genuine E...Night 7k to 12k Chennai City Center Call Girls 👉👉 7427069034⭐⭐ 100% Genuine E...
Night 7k to 12k Chennai City Center Call Girls 👉👉 7427069034⭐⭐ 100% Genuine E...hotbabesbook
 
VIP Mumbai Call Girls Hiranandani Gardens Just Call 9920874524 with A/C Room ...
VIP Mumbai Call Girls Hiranandani Gardens Just Call 9920874524 with A/C Room ...VIP Mumbai Call Girls Hiranandani Gardens Just Call 9920874524 with A/C Room ...
VIP Mumbai Call Girls Hiranandani Gardens Just Call 9920874524 with A/C Room ...Garima Khatri
 
♛VVIP Hyderabad Call Girls Chintalkunta🖕7001035870🖕Riya Kappor Top Call Girl ...
♛VVIP Hyderabad Call Girls Chintalkunta🖕7001035870🖕Riya Kappor Top Call Girl ...♛VVIP Hyderabad Call Girls Chintalkunta🖕7001035870🖕Riya Kappor Top Call Girl ...
♛VVIP Hyderabad Call Girls Chintalkunta🖕7001035870🖕Riya Kappor Top Call Girl ...astropune
 
Call Girls Dehradun Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Dehradun Just Call 9907093804 Top Class Call Girl Service AvailableCall Girls Dehradun Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Dehradun Just Call 9907093804 Top Class Call Girl Service AvailableDipal Arora
 
Book Paid Powai Call Girls Mumbai 𖠋 9930245274 𖠋Low Budget Full Independent H...
Book Paid Powai Call Girls Mumbai 𖠋 9930245274 𖠋Low Budget Full Independent H...Book Paid Powai Call Girls Mumbai 𖠋 9930245274 𖠋Low Budget Full Independent H...
Book Paid Powai Call Girls Mumbai 𖠋 9930245274 𖠋Low Budget Full Independent H...Call Girls in Nagpur High Profile
 
Call Girls Ooty Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Ooty Just Call 9907093804 Top Class Call Girl Service AvailableCall Girls Ooty Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Ooty Just Call 9907093804 Top Class Call Girl Service AvailableDipal Arora
 

Último (20)

VIP Hyderabad Call Girls Bahadurpally 7877925207 ₹5000 To 25K With AC Room 💚😋
VIP Hyderabad Call Girls Bahadurpally 7877925207 ₹5000 To 25K With AC Room 💚😋VIP Hyderabad Call Girls Bahadurpally 7877925207 ₹5000 To 25K With AC Room 💚😋
VIP Hyderabad Call Girls Bahadurpally 7877925207 ₹5000 To 25K With AC Room 💚😋
 
Premium Call Girls Cottonpet Whatsapp 7001035870 Independent Escort Service
Premium Call Girls Cottonpet Whatsapp 7001035870 Independent Escort ServicePremium Call Girls Cottonpet Whatsapp 7001035870 Independent Escort Service
Premium Call Girls Cottonpet Whatsapp 7001035870 Independent Escort Service
 
Top Rated Bangalore Call Girls Richmond Circle ⟟ 8250192130 ⟟ Call Me For Gen...
Top Rated Bangalore Call Girls Richmond Circle ⟟ 8250192130 ⟟ Call Me For Gen...Top Rated Bangalore Call Girls Richmond Circle ⟟ 8250192130 ⟟ Call Me For Gen...
Top Rated Bangalore Call Girls Richmond Circle ⟟ 8250192130 ⟟ Call Me For Gen...
 
College Call Girls in Haridwar 9667172968 Short 4000 Night 10000 Best call gi...
College Call Girls in Haridwar 9667172968 Short 4000 Night 10000 Best call gi...College Call Girls in Haridwar 9667172968 Short 4000 Night 10000 Best call gi...
College Call Girls in Haridwar 9667172968 Short 4000 Night 10000 Best call gi...
 
(Rocky) Jaipur Call Girl - 09521753030 Escorts Service 50% Off with Cash ON D...
(Rocky) Jaipur Call Girl - 09521753030 Escorts Service 50% Off with Cash ON D...(Rocky) Jaipur Call Girl - 09521753030 Escorts Service 50% Off with Cash ON D...
(Rocky) Jaipur Call Girl - 09521753030 Escorts Service 50% Off with Cash ON D...
 
Night 7k to 12k Navi Mumbai Call Girl Photo 👉 BOOK NOW 9833363713 👈 ♀️ night ...
Night 7k to 12k Navi Mumbai Call Girl Photo 👉 BOOK NOW 9833363713 👈 ♀️ night ...Night 7k to 12k Navi Mumbai Call Girl Photo 👉 BOOK NOW 9833363713 👈 ♀️ night ...
Night 7k to 12k Navi Mumbai Call Girl Photo 👉 BOOK NOW 9833363713 👈 ♀️ night ...
 
Call Girls Service Jaipur Grishma WhatsApp ❤8445551418 VIP Call Girls Jaipur
Call Girls Service Jaipur Grishma WhatsApp ❤8445551418 VIP Call Girls JaipurCall Girls Service Jaipur Grishma WhatsApp ❤8445551418 VIP Call Girls Jaipur
Call Girls Service Jaipur Grishma WhatsApp ❤8445551418 VIP Call Girls Jaipur
 
Call Girls Mumbai Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Mumbai Just Call 9907093804 Top Class Call Girl Service AvailableCall Girls Mumbai Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Mumbai Just Call 9907093804 Top Class Call Girl Service Available
 
Call Girls Faridabad Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Faridabad Just Call 9907093804 Top Class Call Girl Service AvailableCall Girls Faridabad Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Faridabad Just Call 9907093804 Top Class Call Girl Service Available
 
Russian Call Girls in Jaipur Riya WhatsApp ❤8445551418 VIP Call Girls Jaipur
Russian Call Girls in Jaipur Riya WhatsApp ❤8445551418 VIP Call Girls JaipurRussian Call Girls in Jaipur Riya WhatsApp ❤8445551418 VIP Call Girls Jaipur
Russian Call Girls in Jaipur Riya WhatsApp ❤8445551418 VIP Call Girls Jaipur
 
Call Girls Kochi Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Kochi Just Call 9907093804 Top Class Call Girl Service AvailableCall Girls Kochi Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Kochi Just Call 9907093804 Top Class Call Girl Service Available
 
Call Girls Jabalpur Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Jabalpur Just Call 9907093804 Top Class Call Girl Service AvailableCall Girls Jabalpur Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Jabalpur Just Call 9907093804 Top Class Call Girl Service Available
 
VIP Call Girls Indore Kirti 💚😋 9256729539 🚀 Indore Escorts
VIP Call Girls Indore Kirti 💚😋 9256729539 🚀 Indore EscortsVIP Call Girls Indore Kirti 💚😋 9256729539 🚀 Indore Escorts
VIP Call Girls Indore Kirti 💚😋 9256729539 🚀 Indore Escorts
 
VIP Service Call Girls Sindhi Colony 📳 7877925207 For 18+ VIP Call Girl At Th...
VIP Service Call Girls Sindhi Colony 📳 7877925207 For 18+ VIP Call Girl At Th...VIP Service Call Girls Sindhi Colony 📳 7877925207 For 18+ VIP Call Girl At Th...
VIP Service Call Girls Sindhi Colony 📳 7877925207 For 18+ VIP Call Girl At Th...
 
Night 7k to 12k Chennai City Center Call Girls 👉👉 7427069034⭐⭐ 100% Genuine E...
Night 7k to 12k Chennai City Center Call Girls 👉👉 7427069034⭐⭐ 100% Genuine E...Night 7k to 12k Chennai City Center Call Girls 👉👉 7427069034⭐⭐ 100% Genuine E...
Night 7k to 12k Chennai City Center Call Girls 👉👉 7427069034⭐⭐ 100% Genuine E...
 
VIP Mumbai Call Girls Hiranandani Gardens Just Call 9920874524 with A/C Room ...
VIP Mumbai Call Girls Hiranandani Gardens Just Call 9920874524 with A/C Room ...VIP Mumbai Call Girls Hiranandani Gardens Just Call 9920874524 with A/C Room ...
VIP Mumbai Call Girls Hiranandani Gardens Just Call 9920874524 with A/C Room ...
 
♛VVIP Hyderabad Call Girls Chintalkunta🖕7001035870🖕Riya Kappor Top Call Girl ...
♛VVIP Hyderabad Call Girls Chintalkunta🖕7001035870🖕Riya Kappor Top Call Girl ...♛VVIP Hyderabad Call Girls Chintalkunta🖕7001035870🖕Riya Kappor Top Call Girl ...
♛VVIP Hyderabad Call Girls Chintalkunta🖕7001035870🖕Riya Kappor Top Call Girl ...
 
Call Girls Dehradun Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Dehradun Just Call 9907093804 Top Class Call Girl Service AvailableCall Girls Dehradun Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Dehradun Just Call 9907093804 Top Class Call Girl Service Available
 
Book Paid Powai Call Girls Mumbai 𖠋 9930245274 𖠋Low Budget Full Independent H...
Book Paid Powai Call Girls Mumbai 𖠋 9930245274 𖠋Low Budget Full Independent H...Book Paid Powai Call Girls Mumbai 𖠋 9930245274 𖠋Low Budget Full Independent H...
Book Paid Powai Call Girls Mumbai 𖠋 9930245274 𖠋Low Budget Full Independent H...
 
Call Girls Ooty Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Ooty Just Call 9907093804 Top Class Call Girl Service AvailableCall Girls Ooty Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Ooty Just Call 9907093804 Top Class Call Girl Service Available
 

Materi Workshop Diabetes Melitus untuk Dokter Umum - Practical Management of Diabetes and Its Complication for General Practitioner

  • 1.
  • 2. 2 Sponsored by PT. Novo Nordisk Indonesia New INSPIRE by PERKENI and STENO Diabetes Center A National Diabetes Management Course
  • 3. 3 Overall Training Objectives ü  To provide participants with a holistic understanding of diabetes management – from diagnosis to late-stage complications ü  To provide participants with practical tools, guidelines, demonstrations and take-home educational materials to improve and optimize their diabetes treatment ü  To emphasize and demonstrate the importance of early treatment of diabetes to avoid long-term complications About INSPIRE Training in Indonesia ¥  Curriculum, workshops and cases designed in collaboration between PB. PERKENI and STENO Diabetes Center ¥  Joint PERKENI – STENO certificates will be distributed for a participation rate of 80% Curriculum Sponsorship ¥  The INSPIRE Training courses, the development of the curriculum and all support programs are sponsored by PT. Novo Nordisk Indonesia to support and enhance the quality of diabetes training across Indonesia Coordination Coordination and Alignment
  • 4. 4 Why INSPIRE? BE INSPIRED AS A DOCTOR… …TO INSPIRE YOUR PATIENTS A TRULY UNIQUE PLACE ¥  An independent research and patient care institution funded by the capital Region of Copenhagen and Novo Nordisk ¥  Patient care, research and education – focusing exclusively on diabetes care and prevention ¥  One of the leading diabetes research and health promotion centers in the world ¥  Treating 6.200 patients with Type 1 and Type 2 Diabetes through the ‘team-based’ method
  • 5. 5 STENO EDUCATION CENTER Facts: ¥  Collaborating with Novo Nordisk and the Capital Region on education of HCPs ¥  Frontiers Steno Symposium ¥  STAR courses in India/Middle East/China ¥  Educational tools ¥  Partnerships with endocrine society's in selected countries (China / Indonesia) Rules of the INSPIRE Program ¥  Certificates can only be given for minimum 80% attendance ¥  Limit Mobile Phone Activity to the Coffee Breaks ¥  Be back on time after lunch- and coffee breaks RULES
  • 6. 6 Why do we see a massive increase in people with Type 2 Diabetes across the World? Cockram CS 2000. HKMJ; 6 (1): 43-52 Mohan et al 2007. Indian J Med Res; 125: 217-230 Adapted from IDF Diabetes Atlas 4th ed., 2009 Aging population Dietary changes Reduced physical activity UrbanisationUnhealthy lifestyle choices
  • 7. 7 Diabetes is developing much faster than anticipated in Indonesia… RISKESDAS Survey 2007 Diagnosed people with Diabetes Undiagnosed people with Diabetes Total people with diabetes Total people with IGT** 1.5% 4.2% 5.7% 10.2% * Source: RISKESDAS Survey 2007 – 24.417 subjects , >15 years ol from 33 provinces ** IFT = Impaired Glucose Tolerance Approximately 10 million people with diabetes in Indonesia …and our diabetes patients are not in good glycemic control DiabCare Indonesia 2008 illustrated the need for more intensive treatment to decrease FPG and PPG n: 1.823 patients with diabetes 208 144 100 140 0 20 40 60 80 100 120 140 160 180 200 220 mg/dl PPG (mg/dl)FPG (mg/dl) GlycemicControlLevel PERKENI GuidelinesDiabCare 2008 Source: Novo Nordisk Data on File
  • 8. 8 Pre-Test & Questionnaire X X Time: 30 minutes Please fill out the Evaluation Scheme after Day 1 and Day 2 In your participant folder
  • 9. 9 Early Detection and Standardized Diabetes Management Lecture: 30 minutes Early Detection and Standardized Diabetes Management Lecture Main Learning Points ¥  Understand the process from screening to diagnosis and the associated national guidelines ¥  Understand the importance of treating diabetes and intensify treatment on diabetes via blood glucose- and HbA1c monitoring ¥  Understand the reason and need for routine follow-up and reaching individual targets to avoid complications
  • 10. 10 Some Definitions before we start… Common Definitions Abbreviation Definition NGT Normal Glucose Tolerance (Gula Darah Normal) FPG Fasting Plasma Glucose (Gula Darah Puasa) PPG Post-Prandial Plasma Glucose (Gula Darah Post Prandial) IGT Impaired Glucose Tolerance (Toleransi Glukosa Terganggu) IFG Impaired Fasting Glucose (Gula Darah Puasa Terganggu) HbA1c Average amount of glucose in the bloodstreams over a 3-month period Classification of Diabetes ¥  Type 1 diabetes ¥  Absolute insulin deficiency due to the destruction of pancreatic beta-cells ¥  Type 2 diabetes ¥  Type 2 is characterized by insulin resistance with relative insulin deficiency to a predominately secretary defect with insulin resistance ¥  Other specific types ¥  Gestational diabetes ¥  Glucose intolerance first detected in pregnancy that often resolves after the birth of the baby Diabetes Care 1997; 20: 1183-1197
  • 11. 11 Difference between Type 1 and Type 2 Diabetes Comparison of Type 1 and Type 2 Diabetes Features Type 1 Diabetes Type 2 Diabetes Onset Sudden Gradual Age at Onset Any age (mostly young) Mostly in adults Body Habitus Thin or normal Often obese Ketoacidosis Common Rare Autoantibodies Usually present Absent Endogenous Insulin Low or absent Normal, decreased or increased Prevalence Less prevalent More prevalent, typically 90-95% of all people with diabetes Type 2 diabetes is a progressive disease Lebovitz. Diabetes Reviews 1999;7:139–53 (data are from the UKPDS population: UKPDS 16. Diabetes 1995;44:1249–58) HOMA: homeostasis model assessment
  • 12. 12
  • 13. 13 Classical Diabetes Symptoms Polyuria Unexplained weight loss Polydipsia Polyphagia ¥  Excessive Urination at night ¥  Excessive Hunger ¥  Excessive Thirst ¥  Weight Loss even if food in-take is normal Other Diabetes Symptoms Blurred Vision Numbness and/or Tingling Fatigue Itchy Skin Impotence ¥  Damaging blood vessels in the eyes ¥  Numbness and tingling in hands, legs and feet ¥  Frequent fatigue regardless of exercise ¥  Affects legs, feet, and hands ¥  Physical and Physiological
  • 14. 14 4 Simple Steps from Screening to Diagnosis Conduct 1st Blood Test 2 Conduct 2nd Blood Test (if required) and establish Diagnosis 3 Screen patients with diabetes risk factors 1 Inform Patient and Initiate treatment 4 Step 1: Risk Factors – PERKENI screening risk factor guideline Unmodifiable Risk Modifiable Risk Diabetes Associated Risk ¥  Race and Ethnic ¥  Family History of Diabetes ¥  History of Gestational Diabetes ¥  History of delivery a baby more than 4.000g ¥  History of low birth weight <2.500g ¥  Overweight (BMI >23) ¥  Hypertension > 140/90 mmHg ¥  Dyslipidemia (HDL < 35 mg/dl and/or triglycerides >250 mg/dl ¥  Unhealthy Diet ¥  Limited Physical Activity ¥  Polycystic Ovary Syndrome (PCOS) or another clinical condition related to insulin resistance ¥  Metabolic Syndrome (IGT, IFG, History of Coronary Artery Disease , stroke and/or PAD) Source: KONSENSUS: Pengelolaan Dan Pencegahan DM Type 2
  • 15. 15
  • 16. 16 Step 4: Inform Patient and Initiate Treatment Diabetes Mellitus IGT IFG ¥  Evaluation of Nutritional Status ¥  Evaluation of Diabetes Complications ¥  Evaluation of Required Food Regulation ¥  Decision on medicines ¥  Education ¥  Food Regulation ¥  Physical Exercise ¥  Ideal Body Weight ¥  OADs are unnecessary at this stage Source: KONSENSUS: Pengelolaan Dan Pencegahan DM Type 2 Cut-points: Diabetes, IGT and IFG mg/dL 2-hour Plasma Glucose (PPG) FastingPlasmaGlucose(FPG) mg/dL 140 200 100 126 NGT (Normal Glucose Tolerance) Diabetes IFG (Impaired Fasting Glucose IGT (Impaired Glucose Tolerance) Diabetes
  • 17. 17 Diagnosis of Type 2 Diabetes KONSENSUS: Pengelolaan Dan Pencegahan DM Type 2 1.  Classical symptoms of Diabetes (+) & Random plasma glucose concentration ≥ 200 mg/dl 2.  Classical symptoms of Diabetes (+) & Fasting Plasma Glucose ≥ 126 mg/dl. 3.  2-hour post-OGTT ≥ 200 mg/dl. Note: ¥  Classical symptom of diabetes (+), only need 1 abnormal BG ¥  No classical symptom of diabetes, need 2 x abnormal BG level in a different days Or Or
  • 18. 18 What is good glycemic control? ¥  Overall aim to achieve glucose levels as close to normal as possible ¥  Minimise development and progression of microvascular and macrovascular complications FPG <130 mg/dL HbA1c < 7.0% PPG <180 mg/dL FPG <110 mg/dl HbA1c < 6.5% PPG <145 mg/dL IDF2 ADA1 PERKENI3 1. American Diabetes Association Diabetes Care 2009;32 (Suppl 1):S1-S97 2. IDF Clinical Guidelines Task Force. International Diabetes Federation 2005. 3. PERKENI 2011 Konsensus . FPG <100 mg/dl HbA1c < 7% PPG <140 mg/dl HbA1c correlation with blood glucose level David M. Nathan, Judith Kuenen, Rikke Borg, Hui Zheng, David Schoenfeld, and Robert J. Heine, for the A1c-Derived Average Glucose (ADAG) Study Group. Diabetes Care 2008 The relationship between A1C and eAG is described by the formula 28.7 X A1C – 46.7 = eAG
  • 19. 19 Risk of Complications increases as Hb1Ac increases and that’s why diabetes must be treated Stratton IM et al. BMJ 2000;321:405–12 0 20 40 60 80 5 6 7 8 9 10 11 Myocardial infarction Microvascular disease Adjusted for age, sex, and ethnic group. The relationship between A1C and mg/dl is described by the formula 28.7 X A1C – 46.7 = mg/dl. Incidenceper1.000patient- years 12697 154 183 212 240 269 Mean HbA1c (%) Mean mg/dl The benefits of good blood glucose control are clear Good control is ≤ 7.0% HbA1c HbA1c measures the average blood glucose level over the last three months Source: UKPDS = United Kingdom Prospective Diabetes Study. Stratton IM et al. BMJ. 2000;321(7258):405-412. Deaths related to diabetes Microvascular complications Myocardial infarction -14% -37% -21% HbA1c -1%
  • 20. 20 Practical Monitoring Scheme Source: Konsensus Pengelolaan dan Pencegahan DMT2 di Indonesia. PERKENI. 2011. Diabetes Care 2012. Penatalaksanaan Diabetes Melitus Terpadu. 2009 Practical Monitoring Scheme Cont… Source: Konsensus Pengelolaan dan Pencegahan DMT2 di Indonesia. PERKENI. 2011. Diabetes Care 2012. Penatalaksanaan Diabetes Melitus Terpadu. 2009
  • 21. 21 Individualized Treatment based on several criteria to control blood glucose Early Detection and Standardized Diabetes Management Lecture Main Learning Points ¥  Understand the importance of treating diabetes and reaching individual targets to avoid complications ¥  Understand the process from screening to diagnosis and the associated national guidelines ¥  Understand the reason and need for routine follow-up and intensify treatment on diabetes via blood glucose- and HbA1c monitoring Summary ¥  Diabetes is a progressive disease that must be treated in order to avoid long-term complications ¥  Good glycemic control according to PERKENI is: ¥  HbA1c <7% ¥  FPG: <100 mg/dl ¥  PPG: <140 mg/dl ¥  Patient treatment need to be individualized according to the characteristics of each particular patients
  • 22. 22 Handout: Overview of Diabetes National Clinical Practice Guidelines Ref: Rudianto et al. The Indonesian Society of Endocrinology’s Summary Article of Diabetes Mellitus National Clinical Practice Guidelines. JAFES Vol. 26 (1), May 2011
  • 23. 23 Diabetes and its Co-morbidities – Hypertension and Dyslipidemia Lecture: 30 minutes Diabetes HypertensionDyslipidemia Diabetes and its Co-morbidities – Hypertension and Dyslipidemia Lecture Main Learning Points • Understand the relationship between diabetes and hypertension • Understand how hypertension should be treated and how diabetic patients with hypertension should be treated • Understand the relationship between diabetes and dyslipidemia • Understand how dyslipidemia should be treated and how diabetic patients with dyslipidemia should be treated
  • 24. 24 Diabetes and its Co-morbidities Hypertension Categories for Blood Pressure Levels in Adults (JNC VII)* * Aged 18 years or older Blood Pressure Level (mmHg) Category Systolic Diastolic Normal < 120 And < 80 Prehypertension 120 -139 Or 80 – 89 High Blood Pressure Stage 1 Hypertension 140 - 159 Or 90 - 99 Stage 2 Hypertension > 160 Or > 100 When systolic and diastolic blood pressures fall into different categories, the higher category should be used to classify blood pressure level. For example, 160/80 mmHg would be stage 2 hypertension (high blood pressure) Why focus on the triangle of diabetes, hypertension and dyslipidemia? Diabetes HypertensionDyslipidemia “Triangular Focus’ Treatment Implications • 40-60% of type 2 diabetes patients will also have either hypertension, dyslipidemia or both • Hypertension and Dyslipidemia are both well established risk factors for diabetes-related complications like CVD and nephropathy • Early and correct treatment of hypertension and dyslipidemia can delay the onset of diabetes complications
  • 25. 25 Diabetes Is a Major Multiplier of Cardiovascular Risk in Patients With Hypertension Systolic Blood Pressure and Cardiovascular Mortality Stamler J, et al. Diabetes Care. 1993;16:434–444. 130 85 62 42 2218 245 153 160 112 73 55 0 50 100 150 200 250 CardiovascularMortality RatePer10,000Person-Years 120 - 139<120 >200 Systolic Blood Pressure mmHg 160 -179 180 - 199140 -159 Diabetes No Diabetes Effect of Blood Pressure Control in the UKPDS Tight vs. Less Tight Control Any diabetes-related endpoint Diabetes-related deaths Heart failure Stroke Myocardial infarction Micro vascular disease Tight Control  1,148 Type 2 patients  Average BP lowered to 144/82 mmHg (controls: 154/87); 9-year follow-up 24 32 56 44 21 37 Risk Reduction (%) P value 0.0046 0.019 0.0043 0.013 NS 0.0092 UKPDS Group. BMJ. 1998;317:703-713.
  • 26. 26 UKPDS hypertension sub-study: Tight blood pressure control reduces complications in diabetes UKPDS Group. BMJ. 1998;317:703-713. Stroke Years 0 20 15 10 5 44% risk reduction P = 0.013 30 5 7 86421 9 Patientswithevents(%) Years Diabetes-related deaths 0 40 30 20 10 30 5 7 86421 9 32% risk reduction P < 0.02 Patientswithevents(%) Less tight control: mean BP 154/87 mmHg Tight control with captopril or atenolol: mean BP 144/82 mmHg Years Microvascular disease Patientswithevents(%) 0 20 15 10 5 30 5 7 86421 9 37% risk reduction P < 0.01 Major Outcomes of the Hypertension Optimal Treatment (HOT) Trial Diabetes Sub-group shows that lowering blood pressure is beneficial for diabetes patients with hypertension Hansson L, et al. Lancet. 1998;351: 1755-1762. 11 8 24 11 4 18 33 11 0 5 10 15 20 25 30 CV Mortality Events/1000Pt-Years MIMajor CV Events <85 mmHG (n=501) <90 mmHG (n=501) <80 mmHG (n=499) Diastolic Target
  • 27. 27 ADA Recommendations on Hypertension Diabetes Care 2012; 35 (Suppl. 1): p29Years Systolic Blood Pressure <130 mmHg, however depending on patient characteristics and response to therapy, higher or lower SBP targets may be appropriate GOAL SBP or DBP 130 – 139 mmHg 80 – 89 mmHg SBP or DBP > 140 mmHg > 90 mmHg • Lifestyle therapy alone for a maximum of 3 months • If targets are not achieved, start treatment with pharmacological agents • Should receive pharmacological therapy in addition to lifestyle therapy JNC 7 Algorithm for Treatment of Hypertension Lifestyle Modifications Initial Drug Choices Not at Goal BP (<140/90 mm Hg) (<130/80 mm Hg for those with diabetes or chronic kidney disease) Without Compelling Indications Stage 1 HTN (SBP 140-159 or DBP 90-99 mm Hg) Thiazide-type diuretics for most. May consider ACEI, ARB, BB, CCB, or combination. Optimize dosages or add additional drugs until goal BP is achieved. Consider consultation with hypertension specialist. Drug(s) for the compelling indications other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB) as needed. Without Compelling Indications Not at Goal BP Stage 2 HTN (SBP 160 or DBP 100 mm Hg) 2-drug combination for most (usually thiazide-type diuretic and ACEI, ARB, BB, or CCB) Chobanian AV et al. JAMA. 2003;289:2560-72
  • 28. 28 ADA Recommendations on Hypertension Cont. Diabetes Care 2012; 35 (Suppl. 1): p29 Lifestyle Treatment Pharmacological Treatment • Weight Control • Increased consumption of fruit, vegetables and low fat diet • Sodium restriction • Increased physical activity • Alcohol moderation • Pharmacologic therapy • A regimen that includes either an ACE I or ARB • If one class is not tolerated, the other should be substituted • Other classes but RAS are equally good. • Multiple drugs are generally required • If ACE I, ARBs, or diuretics are used: • Monitor: kidney function and s- potassium Most relevant drugs are indicated for hypertension patients with diabetes Chobanian, et al.2004
  • 29. 29 Dyslipidemia Dyslipidemia in Diabetes • Total cholesterol • LDL cholesterol • HDL cholesterol • Triglyceride
  • 30. 30 Mean Plasma Lipids at Diagnosis of Type 2 Diabetes UKPDS Number of Pts TC (mg/dl) LDL-C (mg/dl) HDL-C (mg/dl) TG (mg/dl) Type 2 Control MEN * P<0.001, ** P<0.02 comparing type 2 vs. control group 2139 213 139 39** 159* 52 205 132 43 103 Type 2 Control WOMEN 1574 224 151* 43* 159* 143 217 135 55 95 UKPDS Group. Diabetes Care 1997;20:1683-1687. Diabetes & Dyslipidemia • NHANES 1999–2000 prevalence of control of LDL-C, HDL-C, and triglycerides (TG) among those with vs. those without diabetes M.J. Jacobs et al. /Diabetes Research and Clinical Practice 70 (2005) 263–269 Control of LDL-C indicated as <2.6 mmol/l (<100 mg/dl), HDL-C >1.0 mmol/l (40 mg/dl) for men and >1.3 mmol/l (50 mg/dl) for women, and TG <1.7 mmol/l (150 mg/dl).
  • 31. 31 Heart Protection Study Proportions of patients with major vascular events in the Heart Protection Study (HPS) by year of follow-up evaluation and numbers of events prevented with simvastatin treatment per 1,000 individuals The American Journal of Cardiology, Volume 92, Issue 4, Supplement 2, 21 August 2003, Pages 3–9 Meta-analysis of statin treatment in diabetes Risk reduction of clinical outcomes per 40 mg/dL (1.0 mmol/L) reduction in LDL cholesterol • 21% reduction major vascular events • 25% reduction in coronary revascularisation • 21% reduction in stroke • 9% reduction in all-cause mortality • 13% reduction in CVD mortality • No difference in non-vascular mortality Independent of baseline LDL or prior CVD Lancet, 371, 117-25, 2008
  • 32. 32 Updated ATP III LDL-C Goals and Cutpoints for Therapy Grundy SM et al. Circulation 2004;110: 227-239 Risk Category LDL-C (mg/dL) Goal Initiation Level for TLC Consideration Level for Drug Therapy High risk: CHD or CHD risk equivalents (10-yr risk >20%) <100 (optional: <70) ≥100 ≥100 (<100: consider drug options) Moderately high risk: 2+ risk factors (10-yr risk 10–20%) <130 (optional: <100) ≥130 ≥130 (100–129: consider drug options) Moderate risk: 2+ risk factors (10-yr risk <10%) <130 ≥130 ≥160 Lower risk: 0–1 risk factor <160 ≥160 ≥190 (160–189: LDL-C– lowering drug optional) Statin therapy algorithm Third report of the National Cholesterol Education Program (NCEP) Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III): final report. National Heart, Lung, and Blood Institute and National Institutes of Health Website. http://www.nhlbi.nih.gov/guidelines/cholesterol/atp3full.pdf. Accessed November 25, 2009.
  • 33. 33 Conclusions on Statins ADA 2012 • Statin therapy should be considered for all individuals with type 2 diabetes • independent of baseline lipid levels if previously CVD • Statin therapy should be considered for all patients above 40 y with more than 1 risk factor • Especially if • Prior CVD • Albuminuria • Smokers • Hypertension • Severe family history • Lack of data for age < 40y • Should be considered in type 1 diabetes at high risk of CVD or with signs of diabetic complications Risk stratification as per NCEP ATP III guideline Major risk factors as per ATP III guidelines Major risk factors to modify treatment of LDL (excluding LDL cholesterol) Nonmodifiable Modifiable Age: male ≥45 years and female ≥55 years Hypertension: BP ≥140/90 mm Hg or on antihypertensive agents Family history of premature CHD: CHD in male first-degree relative <55 years and in female first- degree relative <65 years Low HDL cholesterol levels: <40 mg/dL (HDL ≥60 mg/dL is protective) Cigarette smoking
  • 34. 34 Fibrates algorithm Fibrates • Greater reductions in triglycerides • Increase HDL cholesterol more effective than statins • Combined treatment (fibrates + statins) decrease triglycerides and LDL cholesterol and increase HDL cholesterol more than statins or fibrates as monotherapy • However, the combination of fenofibrate and simvastatin does not reduce the rate of fatal cardiovascular events, nonfatal MI, or nonfatal stroke, as compared with simvastatin alone
  • 35. 35 Nicotinic Acid • Significant reduction in triglycerides and increases HDL compared to fibrates and statins • Significant effects in combination with statins on Intima Media Thickness (proxy marker of atherosclerosis) compared to statins alone • Adverse effects: vasodilatation (flushing), increases HbA1c, increase uric acid • No data on Nicotinic acid on CVD endpoints Order of Priorities for Treatment of Diabetic Dyslipidemia in Adults Adapted from American Diabetes Association. Diabetes Care 2000;23(suppl 1):S57-S60. LDL Cholesterol Lowering1 • First choice: HMG CoA reductase inhibitor (statin) • Second choice: Bile acid binding resin or fenofibrate HDL cholesterol raising2 • Behavior interventions such as weight loss, increased physical activity and smoking cessation • Glycemic control • Difficult except with nicotinic acid, which is relatively contraindicated, or fibrates. Evidence for treating HDL with drugs is limited and priority should be on lowering LDL Triglyceride lowering3 • Glycemic control first priority • Fibric acid derivative (gemfibrozil, fenofibrate) • Statins are moderately effective at high dose in hypertriglyceridemic subjects who also have high LDL cholesterol
  • 36. 36 Diabetes and its Co-morbidities – Hypertension and Dyslipidemia Lecture Main Learning Points • Understand the relationship between diabetes and hypertension • Understand how hypertension should be treated and how diabetic patients with hypertension should be treated • Understand the relationship between diabetes and dyslipidemia • Understand how dyslipidemia should be treated and how diabetic patients with dyslipidemia should be treated Summary • Measure blood pressure at all visits because hypertension should be treated to prevent complications of diabetes • Target 130/80 mmHg or 125/75 mmHg if proteinuria> 1 gram/24 hrs. • Control lipid profile to prevent cardiovascular event in diabetes • Target of LDL-cholesterol in diabetes: • No CVD :<100 mg/dL • Prior CVD or high risk : <70 mg/dL
  • 37. 37 Non-Pharmacology Intervention Lecture: 30 minutes Non-Pharmacology Intervention Lecture Main Learning Points ¥ The relationship between nutrition and blood glucose control ¥ Understand the eating pattern in the local region that could play a role on the fat or carbohydrate intake ¥ Determine healthy and unhealthy eating and initiating and assessing dietary intervention in a clinical setting ¥ Understand the importance of exercise and the relationship between exercise and blood glucose control ¥ Understand the relationship between smoking and diabetes associated complications
  • 38. 38 Diet & Exercise in Diabetes ¥  Important in type 1 and type 2 diabetes ¥  In type 2 diabetes: ¥  Obesity and physical inactivity are major risk factors ¥  Diet and exercise may provide good long- term glycaemic control in some patients ¥  Improved cardiovascular status ¥  Cost-effective Something went wrong… 2.5 million years 50 years
  • 39. 39 Medical Nutrition Therapy in Diabetes As integral part of : ¥  Prevention and management of diabetes ¥  Component of diabetes education ¥  Prevention of diabetes complication Source: Diabetes Care, Vol. 31, Suppl. 1, 2008 Targets of Medical Nutrition Therapy in prevention and management of Type 2 Diabetes Diabetes Care, Vol. 31, Suppl. 1, 2008 Individual with Diabetes Risk- factors or with pre-diabetes Individual with diagnosed Diabetes 1) To reduce the risk of diabetes and cardiovascular disease by promoting healthy food choices and physical activity leading to moderate weight loss that is maintained. 1)  To achieve and maintain: ¥  Blood Glucose levels in the normal range ¥  A lipid profile that reduces the risk for vascular diseases ¥  Blood Pressure levels in the normal range 2)  To prevent / delay progressivity of chronic complications 3)  To address individual nutrition needs, taking into account personal and cultural preferences and willingness to change
  • 40. 40 The relationship between healthy nutrition and blood glucose Source: Long-term Effects of a Lifestyle Intervention on Weight and Cardiovascular Risk Factors in Individuals with Type 2 Diabetes; Four Yesr Results of the Look AHEAD Trial. The Look AHEAD Reseach Group DSE: Diabetes Support and Education ILI: Intensive Lifestyle Intervention The Fundamentals of food management for diabetes patients Similar with healthy people: ¥  Balance food intake according to calories and nutrition needs for each individual ¥  Weight loss, increased physical activity, and weight management ¥  Consistency in day-to-day carbohydrate intake at meals and snacks ¥  Nutritional content ¥  Timing of meals and snacks ¥  Carbohydrates are the principal determinant for blood glucose Emphasis (‘triple Js)’: ¥  Jadwal (Schedule) ¥  Jenis (Type) ¥  Jumlah (Amount)
  • 41. 41 Calorie Requirement Formula ¥  Harris–Benedict formula ¥  Men = 66 + (13.7 x weight in kg) + (5 x height in cm) - (6.8 x age in years) ¥  Women = 65.5 + (9.6 x weight in kg) + (1.7 x height in cm) - (4.7 x age in years) Frankenfield DC, et al. The Harris-Benedict studies of human basal metabolism: history and limitations. J Am Diet Assoc. 1998;98:439-445 Guidelines for a healthy diet PERKENI 2011 ¥  Healthy balanced diet composed of: ¥  45-65% carbohydrate ¥  20-25% fat ¥  10–20% protein Fat Carbohydrate Protein
  • 42. 42 Carbohydrate Eat Less of These Eat More of These Fruit, Low fat Milk, Beans, Brown rice, Yoghurt, Whole wheat bread White sugar, Brown sugar, White bread, White rice, DASH Pyramid
  • 43. 43 Proteins Eat Less of These Eat More of These Chicken, Fish, TofuSausages, processed meat, Shrimps and shell fish, Red Meat Fat Eat Less of These Eat More of These Avocado, Nuts, Olives, Oils rich in poly and mono unsaturated fats Coconut, Margarine/butter, Cheese, Oils/fats rich in saturated fat
  • 44. 44 Understanding portion sizes is important Recommendation to take smaller portion sizes of the less recommended food Rice boiled – 100 g Calorie – 175 kcal Carbohydrates – 40gm Rice boiled – 200 g Calorie – 350 kcal Carbohydrates – 80gm Noodles boiled – 200 gm Calorie – 175 Kcal Carbohydrates – 40 gm Source: Daftar Bahan Makanan Penukar How you cook is important Less Healthy More Healthy
  • 45. 45 The relationship between exercise and blood glucose Diabetology & Metabolic Syndrome, 2009, 1:27 HbA1c values collected 12 weeks prior to the initiation of the exercise program (Baseline), at the start of the exercise program (Pre-Intervention) and at the completion of the 10 weeks program (Post-Intervention). Ten week changes are denoted by * (p < 0.05). A difference between exercise groups is denoted by # (p < 0.008). Both resistance and aerobic exercise were effective in reducing blood glucose levels and HbA1c levels
  • 46. 46 Boulé NG, et al. JAMA 2001;286:1218-27. -0.66%-0.7 -0.6 -0.5 -0.4 -0.3 -0.2 -0.1 0.0 0.1 0.2 Exercise Non-exercise control ChangeinHbA1c frombaselinetopost-intervention (weightedmeandifference) p<0.001 Effect was weight- independent 0.08% Pooled meta-analysis of 14 exercise trials % Exercise significantly reduces HbA1c Source: Boule NG et al. Effects of exercise on glycemic control and body mass in T2 Diabetes: JAMA2001; 286:1218-27
  • 47. 47 Diabetes and Smoking Background Before diabetes ¥  Smoking is associated with insulin resistance ¥  dose-response relationship between smoking and the risk of type 2 diabetes ¥  Stopping to smoke decreases the risk of type 2 diabetes Additional to diabetes ¥  Smoking increases the risk of developing diabetic complications - nephropathy, neuropathy and retinopathy ¥  Independent risk factor for CVD and all-cause mortality ¥  Smokers are also lipid intolerant ¥  Smoking cessation increases HDL and reduces LDL levels, despite weight gain Facchini. F. S et al Lancet, (1992) 339 (8802) , pp. 1128-1130 . Al-Delaimy WK, et al. Arch Intern Med. 2002;162(3):273-279. Patja, K., et al Journal of Internal Medicine, 258: 356–362. Chaturvedi N, Diabetes Care 1995; 18: 785–92.Jacobs DR Jr et al Arch Intern Med 1999;159: 733-40. Axelsen M., et al (1995), Journal of Internal Medicine, 237: 449–455.D.P. Mikhailidis, et al (1998) The Journal of the Royal Society for the Promotion of Health 118: 91 Significant reduction in mortality of diabetes patients among non-smokers* 591 368323275215 1,984 1,443 1,2191,249 1,012 0 500 1,000 1,500 2,000 MortalityRate(per100.000person-years) Past 1-14 cig / dayNever 15-34 cig / day 35+ cig / day Non-diabetic woman Diabetic woman Source: Wael K. Al-Delaimy et al. Diabetes Care 24: 2043-2048, 2001 cig = cigarette RR of mortality 1.31 1.43 1.64 2.19 * Adjusting BP, high cholesterol & other CV risk factors
  • 48. 48 Practical Initiation of Diet Programs for diabetes patients Food Mapping Systems Food Mapping System can be used for patient education to increase patient compliance with diet scheme Beras Merah Kukus Nasi Putih Nasi Goreng Ayam Bakar Ayam Goreng Ayam Goreng Tepung Ikan Bakar / Kukus Ikan Goreng Udang Goreng Sayur Kukus Kukus Dim Sum Dim Sum Goreng Group Discussion
  • 49. 49 Practical Initiation of Diet Programs for diabetes patients Healthy Plate Models T-shaped plate model to loose weight Y-shaped plate model to maintain weight Portion Control Plate was effective in inducing weight loss and decreased use of hypoglycemic medications in obese patients with type 2 diabetes mellitus Vegetables Carbo- hydrate / Starch Protein Carbo- hydrate / Starch Vegetables Protein Pedersen DE et al. Arch Intern Med. 2007; 167 Practical Initiation of Exercise Programs for diabetes patients CRIPE Pricnciple CRIPE: Continuous, Rhytmic, Interval, Progressive, Endurance Continuous ¥  Exercises should be done continuously without rest (e.g. 30 minutes of jogging without rest) Rhythmic ¥  Choose more rhythmical sports where regular contraction and relaxation are possible (e.g. walking, jogging, running and swimming) Interval ¥  Exercises with both quick and slower actions (e.g. running followed by jogging) Progressive ¥  Increase intensity according to abilities (heart rate target: 75-85% from maximum heart rate) Endurance ¥  Exercise for endurance to improve cardiorespiratory abilities (e.g. walking, jogging, swimming, cycling)
  • 50. 50 Non-Pharmacology Intervention Lecture Main Learning Points ¥  The relationship between nutrition and blood glucose control ¥  Understand the eating pattern in the local region that could play a role on the fat or carbohydrate intake ¥  Determine healthy and unhealthy eating and initiating and assessing dietary intervention in a clinical setting ¥  Understand the importance of exercise and the relationship between exercise and blood glucose control ¥  Understand the relationship between smoking and diabetes associated complications Summary ¥  It’s importance to educate the patients about diet, exercise and non-smoking recommendations as sufficient evidence is available about the improvement in HbA1c levels through lifestyle intervention ¥  Simple patient supporting tools like food mapping system or the CRIPE exercise principle are readily available ¥  It is important to negotiate with the patients on which food choices are the healthiest based upon the patient eating patterns
  • 51. 51 Diabetes Acute Complications – Hypoglycemia and DKA Lecture: 30 minutes Management of Hypoglycemia Lecture Main Learning Points • Understand the hypoglycemia mechanism, diagnosis and how hypoglycemia should be treated • Understand how to adjust OAD - or insulin dosage after hypoglycemic events • Understand what causes a DKA event, how DKA is treated and what to do if you experience a patient with DKA
  • 52. 52 Why address hypoglycemia in diabetes training • Reducing HbA1c levels associated with prevention or delay in complications and death • Hypoglycaemia is a limiting factor in achieving glycaemic targets • Hypoglycaemia is associated with morbidity and rarely even be fatal • Optimising glycaemic control is of obvious importance: • $465 billion USD spent to treat diabetes and its complications in 2011; hypoglycaemia is cost-intensive • 6.8% of global all-cause mortality attributed to diabetes in 2010 (4 million deaths) Cryer et al 2003. Diabetes Care; 26,6: 1902-1912. IDF Diabetes Atlas tth ed., 2009. Roglic and Unwin 2010. Diabetes Research and Clinical Practice; 87: 15-19 What is hypoglycemia? neurogenic symptoms due to low plasma glucose levels • Low plasma glucose levels defined as: • ≤70 mg/dL (ADA)1 • <60 mg/dl (PERKENI)2 • <72 mg/dL (CDA)3 • Symptoms respond to the administration of carbohydrate3 1. ADA. Diabetes Care 2005;28:1245–9; 2. PERKENI Konsensus 2011. 3. Yale et al. Canadian J Diabetes 26:22–35 ADA, American Diabetes Association; CDA, Canadian Diabetes Association; A state of neuroglycopenic and/or neurogenic symptoms due to low plasma glucose levels
  • 53. 53 Most common symptoms of Hypoglycemia Patients (%) Circumoral paraesthesia Difficulties in concentration Slurred speech Blurred vision 0 20 40 60 80 100 Hunger Palpitations Vertigo Cold feeling Anxiety Euphoria Weakness Tremor Sweating Headache Nausea Pramming 1991 Sequel of hypoglycaemia • Mild symptomatic hypoglycaemia • No direct serious clinical effects • May impair subsequent hypoglycaemia awareness • Severe hypoglycaemia associated with • Stroke and transient ischaemic attacks • Memory loss/cognitive impairment • Myocardial infarction • Injury (direct/indirect) • Death Turner et al. (UKPDS 33), 1998. The Lancet; 352: 837-853
  • 54. 54 Risk Factors of Hypoglycemia • General risk factors for hypoglycaemia:1,2 • delayed or missed meal • consuming a smaller meal than planned • exercise • use of diabetes medications • drug/alcohol consumption • increased insulin sensitivity or decreased insulin clearance • Risk factors for major hypoglycaemia:3,4 • age/duration of diabetes treatment • intensive glycaemic control • hypoglycaemia unawareness • sleep • antecedent hypoglycaemia • history of major hypoglycaemia 1.Briscoe & Davis. Clin Diabetes 2006;24:115–21; 2. ADA Workgroup on Hypoglycemia. Diabetes Care 2005;28:1245–9. 3. Frier. Diabetes Metab Res Rev 2008;24:87–92; 4. Cryer. Diabetes 2008;57:3169–76 Hypoglycaemic events occur more often in Type 1 diabetes patients and are less frequent and less severe in Type 2 diabetes patients both on conventional and intensive therapy Adapted from DCCT Research Group. Diabetes 1997. Adapted from Bonds D., data presented at ADA 2009 Eventsper100PatientYears HbA1c (%) Conventional Therapy 0 10 20 30 40 50 60 70 80 90 100 6.0 6.5 7.0 7.5 8.0 8.5 9.0 ACCORD (T2 DM) DCCT (T1 DM) Eventsper100PatientYears HbA1c (%) Intensive Therapy 0 10 20 30 40 50 60 70 80 90 100 6.0 6.5 7.0 7.5 8.0 8.5 9.0 DCCT (T1 DM) ACCORD (T2 DM)
  • 55. 55 Treatment of mild Hypoglycemia First: 10–20 g fast-acting carbohydrate, e.g.: • 3–6 glucose tablets* • 90–180 ml fizzy drink or squash (not diet)** • Two teaspoons of sugar added to a cup of cold drink • 50–100 ml energy drink (e.g. Lucozade®)* Then: • If next meal is due, add extra carbohydrate • If next meal is not due, eat longer-acting carbohydrate, such as biscuits or a sandwich Treating early signs RCN 2004 *not widely available in Indonesia ** Indonesia  processed drinks (tea, etc) Prevention of Hypoglycemic Events • Education • Symptoms • Self management • Proper food intake in therapy • For elderly patients, caregiver should also be educated • Repetitive education in patients with decreased cognitive function • Self monitoring blood glucose (SMBG) • Exercise planning • Measuring blood glucose before exercise • Consuming carbohydrate • Adjust insulin dose based on the blood glucose level • Right type and dose for therapy
  • 56. 56 Treatment of moderate-to-major Hypoglycemia Patient requires assistance with treatment If conscious: • Carer should help the patient to consume 10–20 g fast-acting carbohydrate • Dextrose gel* may be useful If unconscious: • Don’t put anything in patient’s mouth • IM or SC glucagon* or IV glucose should be administered • Emergency services should be called Treating late signs RCN 2004; Cryer 2010 IM: intramuscular, SC: subcutaneous, IV: intravenous Adjusting Dosage after a Hypoglycemic Event If hypoglycemic events are repeated, OAD and / or Insulin dosages should be reduced OAD: Depending on drug Insulin: Initially decrease with 2 units / day
  • 57. 57 Diabetes Ketoacidosis What is Diabetes Ketoacidosis Watkins et al. In: Diabetes and its Management 2003  Acute decompensated metabolic state due to  severe insulin deficiency  over-activity of glucagon & other counter-regulatory hormone  Common in Type 1; Rare in Type 2  Potentially life-threatening  High mortality  Incidence : 5-8 /1000 diabetic persons/yr  Mortality rates 9-14 % - Has improved with insulin use 2%
  • 58. 58 How to Diagnose Diabetes Ketoacidosis  Anorexia  Nausea  Vomiting  Thirst  Polyuria  Weakness  Abdominal pain  Weight loss  Tachycardia  Hypotension  Hypothermia  Impaired consciousness  Warm dry skin  Kussmaul respiration  Acetone odour on breath Symptoms Signs Why are patients developing ketoacidosis The most common events that cause a person with diabetes to develop diabetic ketoacidosis are:  infection such as diarrhea, vomiting, and/or high fever (40%)  missed or inadequate insulin (25%)  newly diagnosed or previously unknown diabetes (15%)  Various other causes may include a heart attack, stroke, trauma, stress, alcohol abuse, drug abuse, and surgery.  Approximately 5% to 10% of cases have no identifiable cause
  • 59. 59 Diabetes Ketoacidosis Definitions Diabetes Care, Vol. 29, Number 12, December 2006 DKA is defined as:  Increase serum concentration of ketones greater than 5 mEq/L (beta hydroxybutirate acid > 0,6)  Blood glucose level greater than 250 mg/dL (although it is usually much higher),  Blood pH less than 7.3  Ketonemia and ketonuria are characteristic, as is a serum bicarbonate level of 18 mEq/L or less (< 5 mEq/L is indicative of severe DKA) Objectives and Management of DKA Treatment 1. Search & treat precipitating cause 2. Replacing fluids 3. Insulin iv (rapid / short- acting) 4. Replacing electrolytes - potassium & magnesium- if required 5. For GPs: If you observe a DKA case, immediately send the patient to the hospital 1. To normalize blood glucose as soon as possible with Insulin 2. To replace fluids and reverse ketoacidosis 3. Monitoring: • Vital signs • Fluid and electrolyte balance • Glycaemia Objectives Management
  • 60. 60 Initial DKA Treatment in Primary Care 1. Evaluate vital signs and urine volume 2. IV line, start the rehydration 3. Check the blood glucose periodically (per hour if possible) Prepare the patient for Hospital 12:00 12:30 1:00 2:00 30 min. 30 min. 60 min. • Start insulin with bolus IV 180 mU/kgBW, and continue with insulin drip 90 mU/hour/kgBW • Check blood glucose per hour with glucometer on the way to hospital Diabetes Acute Complication – Hypoglycemia and DKA Lecture Main Learning Points • Understand the hypoglycemia mechanism and how hypoglycemia should be treated • Understand how to adjust OAD - or insulin dosage after hypoglycemic events • Understand what causes a DKA event, how DKA is treated and what to do if you experience a patient with DKA Summary • The risk of hypoglycemia is one of the key limiting factors in reaching optimal glucose targets • For Insulin, hypoglycemia is mainly a phenomenon occurring in Type 1 diabetes patients • Prevention of hypoglycemia requires patient education, frequent blood glucose monitoring and exercise planning • If hypoglycemia occur repeatedly, reduce the dosage of OAD and/or Insulin • DKA should be regarded as an emergency situation and prompt treatment with insulin is vital
  • 61. 61 Initiating Diabetes Treatment with OADs Lecture: 30 minutes Initiating Diabetes Treatment with OADs Lecture Main Learning Points • Understand the different classes of OADs and when to use which OADs – either as mono therapy or in combination with other OAD’s / Insulin
  • 62. 62 Factors to Consider when Choosing an Anti- hyperglycemic agent Effectiveness in lowering glucose Extraglycaemic effects that may reduce long-term complications Safety profile Tolerability Cost Effect on body weight Nathan DM et al. Diabetes Care 2006;29(8):1963-72. Treatment therapies for Type 2 diabetes When and How to start treatment Adapted from Raccah et al. Diabetes Metab Res Rev 2007;23:257. Lifestyle + Metformin +-other OAD or GLP-1 agonists HbA1c ≥7.0% Basal Basal Insulin Premix Insulin Basal + Bolus Insulin START TREATMENT OAD TREATMENT START INSULIN INSULIN INTENSIFICATION
  • 63. 63 Updated PERKENI Type 2 Diabetes Treatment Algorithm Diabetes STEP 1 STEP 2 STEP 3 Healthy life style Healthy life style + Mono therapy Healthy life style + 2 OAD Combination Healthy life style + Combination 2 OAD + Basal insulin Insulin Intensification* *Intensive Insulin: use of basal insulin together with insulin prandial Healthy life style + 3 OAD Combination Alternative option, if : • No insulin is available • The patient is objecting insulin • Blood glucose is still not optimally controlled Note: 1. Therapy failed if target of HbA1c < 7% is not achieved within 2-3 months for each step 2. In case of no HbA1c test, the use of blood glucose level is also permitted. Average blood glucose level for a few BG test in one day can be converted to HbA1c (ref: ADA 2010) Updated PERKENI Type 2 Diabetes Treatment Algorithm
  • 64. 64 ADA/EASD Algorithm Main pathophysiological defects in type 2 DM hepatic glucose production peripheral glucose uptake pancreatic insulin secretion pancreatic glucagon secretion gut carbohydrate delivery and absorption incretin effect Hyperglycemia ? Liver Muscle PancreasIntestines Adipose Brain Kidney Glucose reabsorpsion Adapted from:Inzucchi SE, Sherwin RS. Diabetes Mellitus. In: Goldman L, Ausiello D, eds. Cecil Textbook of Medicine. 23rd Edn. Philadelphia, Pa: Saunders Elsevier; 2007.
  • 65. 65 Current available OADs and non-Insulin injectables in Indonesia • Metformin • Sulfonylureas (SUs) and glinides • α-glucosidase inhibitors (AGIs) • Glucagon-like peptide-1 (GLP-1) agonists • Thiazolidinediones (TZDs) • Dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) Metformin Mode of Action The primary effects of metformin are to decrease hepatic glucose production and increase insulin-mediated peripheral glucose uptake  Anaerobic glucose metabolism  Glucose uptake Adipose tissueMuscle Liver  Glucose uptake  Glucose oxidation Glucose oxidation  Glycogenesis Intestine  Oxidation of FA  Gluconeogenesis  Glycogenolysis  Oxidation of FA Krentz AJ, Bailey CJ. Drugs 2005;65:385–411. FA: Fatty Acids
  • 66. 66 Metformin Clinical Overview and Contraindications Metformin Efficacy* Safety, Tolerability and Adherence Contraindications Advantages • HbA1c reduction of 1-2% • FPG reduction of 40-70 mg/dl • Associated with diarrhea and abdominal discomfort • Lactic acidosis if improperly prescribed • Renal insufficiency • Liver failure • Heart failure • Severe gastrointestinal disease • Do not cause hypoglycaemia when used as mono-therapy • Do not cause weight gain; may contribute to weight loss Krentz AJ, Bailey CJ. Drugs 2005;65:385–411. * Efficacy depends on existing blood glucose levels Metformin Little benefit – if any - to go above 2.000 mg Fasting Plasma Glucose HbA1c 61.9 77.9 40.9 31.0 18.9 0 10 20 30 40 50 60 70 80 Changevs.Placebo(mg/dl) 2500mg2000mg1500mg1000mg500mg Garber AJ, Am J Med 1997;102:491-7. Metformin Dose 1.6 2.0 1.7 1.2 0.9 0.0 0.5 1.0 1.5 2.0 Changevs.Placebo(%) 2500mg2000mg1500mg1000mg500mg Metformin Dose
  • 67. 67 SUs and Glinides Mode of Action • Sulfonylureas (SUs) and glinides increase endogenous insulin secretion by binding to pancreatic β-cells and triggering a cascade of intracellular events1–3 • The mode of action of SUs and glinides is similar, but stimulation of insulin secretion is more rapid and short-acting with glinides • SU receptors are also found on other cells, including the cardiac myocytes 1. Gallwitz B, Haring H-U. Diabetes Obes Metab 2010;12:1–11. 2. Schuit FC, et al. Diabetes 2001;50:1–11. 3. Krentz AJ, Bailey CJ. Drugs 2005;65:385–411. SU: sulfonylurea; GLUT: glucose transporter. Pancreatic β-cell Glucose uptake Insulin release Voltage-gated calcium channel ATP-sensitive potassium channel SUs / glinides Glycolysis respiration Glucokinase ATP Ca2+ ATP = orange Ca2+ = light green SUs and Glinides Clinical Overview Sulphonylurea Efficacy* Safety, Tolerability and Adherence • HbA1c reduction of 1-2% • FPG reduction of 40-70 mg/dl • Associated with hypoglycaemia and weight gain Krentz AJ, Bailey CJ. Drugs 2005;65:385–411. Nathan DM, et al. Diabetologia. 2009;52:17–30. Rosenstock J, et al. Diabetes Care. 2004;27:1265–70. * Efficacy depends on existing blood glucose levels Glinides Efficacy* Safety, Tolerability and Adherence • HbA1c reduction of 0.5-1.5% • FPG reduction of 20-60 mg/dl • PPG reduction of 75-100 mg/dl • Associated with hypoglycaemia and weight gain • Frequent administration (with every meal) is required.
  • 68. 68 Alpha glucosidase inhibitors Mode of Action • Slow digestion of sucrose and starch and therefore delay absorption • Slow post-meal rise in blood glucose • Side effects • Flatulence, abdominal discomfort , diarrhoea • As mono-therapy will not cause hypoglycaemia • Hypoglycaemia when used with other medicine (e.g. a sulphonylurea) 1. Gallwitz B, Haring H-U. Diabetes Obes Metab 2010;12:1–11. 2. Schuit FC, et al. Diabetes 2001;50:1–11. 3. Krentz AJ, Bailey CJ. Drugs 2005;65:385–411. Alpha glucosidase inhibitors Clinical Overview Alpha glucosidase inhibitors Efficacy* Safety, Tolerability and Adherence • HbA1c reduction of 0.5-1% • FPG reduction of 10-20 mg/dl • PPG reduction of 40-50 mg/dl • Associated with flatulence, diarrhea and abdominal discomfort • As mono-therapy will not cause hypoglycaemia • Frequent administration (with every meal) is required. Krentz AJ, Bailey CJ. Drugs 2005;65:385–411. Nathan DM, et al. Diabetologia. 2009;52:17–30. Rosenstock J, et al. Diabetes Care. 2004;27:1265–70. * Efficacy depends on existing blood glucose levels
  • 69. 69 Thiazolidinediones (TZDs) Mode of Action Thiazolidinediones (TZDs) increase the sensitivity of muscle and adipose cells to insulin and suppressing hepatic glucose production Krentz AJ, Bailey CJ. Drugs 2005;65:385–411. TZD: Thiazolidinediones  Glucose uptake  Glucose uptake  Gluconeogenesis *Inconsistent findings Adipose tissue Muscle Liver  Fatty acid uptake  Lipogenesis  Pre-adipocyte differentiation  Glycolysis  Glucose oxidation  Glycogenesis*  Glycogenolysis  Lipogenesis  Glucose uptake* Thiazolidinediones Clinical Overview Krentz AJ, Bailey CJ. Drugs 2005;65:385–411. Drug Class Review: Thiazolidinediones. Available at: http://pharmacy.oregonstate.edu/drug_policy/pages/dur_board/reviews/articles/TZD_ClassReview.pdf . Rizzo M, et al. Expert Opin Pharmacother. 2008;9:2295–303. * Efficacy depends on existing blood glucose levels Thiazolidinediones Efficacy* Safety, Tolerability and Adherence Contraindications Advantages • HbA1c reduction of 0.5-1.5% • FPG reduction of 20-55 mg/dl • Associated with weight gain and edema • Contraindicated in patients with abnormal liver function • Warnings regarding risk of fractures • May exacerbate or precipitate congestive heart failure • Liver disease, heart failure or history of heart disease • Pregnancy and breast feeding • Reduced levels of LDL- cholesterol and increased level of HDL- cholesterol
  • 70. 70 DPP-4 inhibitors Mode of Action Drucker DJ et al. Nature 2006;368:1696–705. Idris I, et al. Diabetes Obes Metab 2007;9:153–65. Barnett A. Int J Clin Pract 2006;60:1454–70. Gallwitz B, et al. Diabetes Obes Metab 2010;12:1–11. DPP-4: dipetidyl peptidase-4; GI: gastrointestinal; GIP:glucose-dependent insulinotropic polypeptide; GLP-1: glucagon-like peptide Increases and prolongs GLP-1 effect on α-cells Increases and prolongs GLP-1 and GIP effects on β-cells Food intake Stomach GI tract Intestine α-cells Pancreas Glucose-dependent insulin secretion β-cells DPP-4 inhibitor Glucose-dependent glucagon secretion Incretins (GLP-1, GIP) DPP-4 Net effect: blood glucose * GIP does not inhibit glucagon secretion by α-cells DPP-4 inhibitors Clinical Overview DPP-4 inhibitors Efficacy* Safety, Tolerability and Adherence • HbA1c reduction of 0.5-1% • FPG reduction of 20 mg/dl • PPG reduction of 45-55 mg/dl • Generally well tolerated • Low risk of hypoglycemia • Not associated with weight gain • Upper respiratory tract infection5 has been reported in clinical studies • Most require only once daily administration Ahrèn B. Expert Opin Emerg Drugs 2008;13:593–607. Gallwitz B, et al. Diabetes Obes Metab 2010;12:1–11. Amori RE, et al. JAMA 2007;298:194–206. Saxagliptin, FDA’s Endocrinologic and Metabolic Drugs Advisory Committee Briefing Document for April 2009 Meeting: NDA 22-350. Available at: http://www.fda.gov/OHRMS/DOCKETS/ac/09/briefing/2009-4422b1-02-Bristol.pdf. (accessed Nov 2010). Aschner P, et al. Diabetes Care 2006;29:2632–7. * Efficacy depends on existing blood glucose levels
  • 71. 71 GLP 1 Agonist Mode of Action 1. Doyle ME, Egan JM. Pharmacol Ther 2007;113(3):546–93. GLP-1: glucagon-like peptide Glucagon-like peptide-1 (GLP-1) agonist activates the GLP receptor in the pancreas. This increases insulin release from the pancreatic β-cells, while inhibiting glucagon release by the pancreatic α-cells α-cell Pancreas • Glucose-dependent insulin biosynthesis and secretion • β-cell proliferation β-cells • Glucagon secretion • β-cell apoptosis GLP-1 agonist Net effect: blood glucose GLP 1 Agonist Clinical Overview GLP-1 Agonist Efficacy* Safety, Tolerability and Adherence • HbA1c reduction of 1-2% • FPG reduction of 6-12 mg/dl • PPG reduction of 6-18 mg/dl • Associated with moderate and transient nausea, vomiting and diarrhoea • Low risk of hypoglycemia and no evidence of increased CV risk • Associated with weight reduction • Associated with reduction in BP Garber AJ. Diabetes Care 2011;34 (Suppl 2):S279–84. Moretto TJ, et al. Clin Ther 2008;30:1448–60. Drucker DJ. Cell Metab 2006;3:153–65. Amori RE, et al. JAMA 2007;298:194–206. * Efficacy depends on existing blood glucose levels
  • 72. 72 The Principles of OAD Combination Theory • Two (or more) oral blood glucose-lowering medicines that have different mechanisms of action • Two medications is better rather than increase in initial medicine to maximum dosage • Fewer side effects than mono-therapy at higher doses Diabetes in elderly people • Always start with the lowest dose of any blood glucose-lowering medicine and increase gradually • Using shorter-acting medicines that reduces the risk of hypoglycaemia • Hypoglycaemia may increase the risk of falls and heart attack in older people  Remember the possibility of • Forgetfulness • Poor motivation • Depression • Cognitive deficits • Poly-pharmacy • Reduced manual dexterity • These factors impact on the ability to maintain self-care and achieve maximum benefits from blood glucose-lowering medicines.
  • 73. 73 OAD’s – a quick summary of the different mechanism of actions α-Glucosidase inhibitors Delay intestinal carbohydrate absorption Thiazolidinediones Increase glucose uptake in skeletal muscle and decrease lipolysis in adipose tissue Sulfonylureas Increase insulin secretion from pancreatic β-cells GLP = glucagon-like peptide. Adapted from Cheng and Fantus. CMAJ. 2005;172:213–226. Meglitinides Increase insulin secretion from pancreatic β-cells Incretins :GLP-1 analogue(exen- atide)/DPP-4 inhibitors Improves glucose-dependent insulin secretion from pancreatic β-cells, suppresses glucagon secretion from α-cells, slows gastric emptying Properties of available glucose-lowering agents that may guide treatment choice in Type 2 Diabetes Class Compounds(s) Cellular mechanism Primary Physiological action(s) Advantages Disadvantages Biguanides Metformin Activates AMP-kinase Hepatic Glucose Production ↓ Extensive Experience No weight gain No hypoglycaemia Likely CVD Events ↓ Gastrointestinal side effects Lactic acidosis risk (rare) Vitamin B12 deficiency Multiple contraindications: CKD, acidosis, hypoxia, dehydration etc. Sulfonylureas Glibenclamide / glyburide Glipizide Gliclazide Glimepiride Closes KATP channels on beta cell plasme membranes Insulin secretion ↑ Extensive experience Microvascular Risk ↓ (UKPDS) Hypoglycemia Weight gain Blunts myocardial ischaemic preconditioning ? Low durability Meglitinides Repaglinide Nateglinide Closes KATP channels on beta cell plasme membranes Insulin secretion ↑ Postprandial glucose excursions ↓ Dosing flexibility Hypoglycemia Weight gain Blunts myocardial ischaemic preconditioning ? Frequent dosing schedule Inzucci SE, et al. Diabetologia. 2012
  • 74. 74 Properties of available glucose-lowering agents that may guide treatment choice in Type 2 Diabetes cont. Class Compounds(s) Cellular mechanism Primary Physiological action(s) Advantages Disadvantages Thiazolidinedi ones Pioglitazone Rosiglitazone Activates the nuclear transcription factor PPAR-y Insulin Sensitivity ↑ No hypoglycaemia Durability HDL-C ↑ Triacylglycerol ↓ (pioglitazone) CVD Events ↓? Weight Gain Oedema / Heart Failure Bone Fractures LDL-C ↑ (rosiglitazone) Mn ↑ (meta- analyses, rosiglitazone) Bladder Cancer ↑? (pioglitazone) a-Glucosidase Inhibitors Acarbose Migitol Voglibose Inhibits intestinal a- glucosidase Slows intestinal carbohydrate digestions / absorption No hypoglycaemia Postprandial glucose excursions ↓ CVD Events ↓ Non-systemic Modest HbA1c efficacy Gastrointestinal side effects (flatulence, diarrhoea) Frequent dosing schedule DPP-4 Inhibitors Sitagliptin Vildagliptin Saxagliptin Linagliptin Alogliptin Inhibits DPP-4 activity, increasing postprandial active incretin (GLP-1, GIP) concentrations Insulin secretion ↑ (glucose-dependent) Glucagon secretion ↓ (glucose-dependent) No hypoglycaemia Well tolerated Modest HbA1c efficacy Urticardia/Angio- oedema Pancreatitis ? Inzucci SE, et al. Diabetologia. 2012 Properties of available glucose-lowering agents that may guide treatment choice in Type 2 Diabetes cont. Class Compounds(s) Cellular mechanism Primary Physiological action(s) Advantages Disadvantages GLP-1 Receptor Agents Exenatide Liraglutide Activates GLP- 1 receptors Insulin secretion ↑ (glucose-dependent) Glucagon secretion ↓ (glucose-dependent) Slows gastric emptying Satiety ↑ No hypoglycaemia Weight reduction Improved beta cell mass / function ? Cardiovascular protective actions ? Gastrointestinal side effects (nausea / vomiting) Acute pancreatitis ? C cell hyperplasia / medullary thyroid tumours Injectable Training Requirements Insulin Human NPH Human Regular Lispro Aspart Gluisine Glargine Determir Pre-mixed (several types) Activates insulin receptors Glucose disposal ↑ Hepatic glucose production ↓ Universally effective Theoretically unlimited efficacy Microvascular Risk ↓ (UKPDS) Hypoglycemia Weight gain Mitogenic effects ? Injectable Training Requirements ‘Stigma’ for patients Inzucci SE, et al. Diabetologia. 2012
  • 75. 75 Initiating Diabetes Treatment with OADs Lecture Main Learning Points • Understand the different classes of OADs and when to use which OADs – either as mono therapy or in combination with other OAD’s / Insulin Summary • Different start and intensification options for OADs exist depending on the need for the individual patient • Metformin will generally be the first drug of choice
  • 76. 76 Propertiesofavailableglucose-loweringagentsthatmay guidetreatmentchoiceinType2Diabetes ClassCompounds(s)Cellular mechanism Primary Physiological action(s) AdvantagesDisadvantages BiguanidesMetforminActivates AMP-kinase HepaticGlucose Production↓ Extensive Experience Noweightgain Nohypoglycaemia LikelyCVDEvents↓ Gastrointestinalside effects Lacticacidosisrisk (rare) VitaminB12 deficiency Multiple contraindications: CKD,acidosis, hypoxia, dehydrationetc. SulfonylureasGlibenclamide/ glyburide Glipizide Gliclazide Glimepiride ClosesKATP channelson betacell plasme membranes Insulinsecretion↑Extensive experience MicrovascularRisk↓ (UKPDS) Hypoglycemia Weightgain Bluntsmyocardial ischaemic preconditioning? Lowdurability MeglitinidesRepaglinide Nateglinide ClosesKATP channelson betacell plasme membranes Insulinsecretion↑Postprandial glucoseexcursions↓ Dosingflexibility Hypoglycemia Weightgain Bluntsmyocardial ischaemic preconditioning? Frequentdosing schedule InzucciSE,etal.Diabetologia.2012
  • 77. 77 Propertiesofavailableglucose-loweringagentsthatmay guidetreatmentchoiceinType2Diabetescont. ClassCompounds(s)Cellular mechanism Primary Physiological action(s) AdvantagesDisadvantages Thiazolidinedi ones Pioglitazone Rosiglitazone Activatesthe nuclear transcription factorPPAR-y InsulinSensitivity↑No hypoglycaemia Durability HDL-C↑ Triacylglycerol↓ (pioglitazone) CVDEvents↓? WeightGain Oedema/Heart Failure BoneFractures LDL-C↑ (rosiglitazone) Mn↑(meta- analyses, rosiglitazone) BladderCancer↑? (pioglitazone) a-Glucosidase Inhibitors Acarbose Migitol Voglibose Inhibits intestinala- glucosidase Slowsintestinal carbohydrate digestions/ absorption No hypoglycaemia Postprandial glucose excursions↓ CVDEvents↓ Non-systemic ModestHbA1c efficacy Gastrointestinalside effects(flatulence, diarrhoea) Frequentdosing schedule DPP-4 Inhibitors Sitagliptin Vildagliptin Saxagliptin Linagliptin Alogliptin InhibitsDPP-4 activity, increasing postprandial activeincretin (GLP-1,GIP) concentrations Insulinsecretion↑ (glucose-dependent) Glucagonsecretion↓ (glucose-dependent) No hypoglycaemia Welltolerated ModestHbA1c efficacy Urticardia/Angio- oedema Pancreatitis? InzucciSE,etal.Diabetologia.2012
  • 78. 78 Propertiesofavailableglucose-loweringagentsthatmay guidetreatmentchoiceinType2Diabetescont. ClassCompounds(s)Cellular mechanism Primary Physiological action(s) AdvantagesDisadvantages GLP-1 Receptor Agents Exenatide Liraglutide ActivatesGLP- 1receptors Insulinsecretion↑ (glucose-dependent) Glucagonsecretion↓ (glucose-dependent) Slowsgastric emptying Satiety↑ No hypoglycaemia Weightreduction Improvedbeta cellmass/ function? Cardiovascular protective actions? Gastrointestinalside effects(nausea/ vomiting) Acutepancreatitis? Ccellhyperplasia/ medullarythyroid tumours Injectable Training Requirements InsulinHumanNPH HumanRegular Lispro Aspart Gluisine Glargine Determir Pre-mixed (severaltypes) Activates insulin receptors Glucosedisposal↑ Hepaticglucose production↓ Universally effective Theoretically unlimited efficacy Microvascular Risk↓(UKPDS) Hypoglycemia Weightgain Mitogeniceffects? Injectable Training Requirements ‘Stigma’forpatients InzucciSE,etal.Diabetologia.2012
  • 79. 79 The Usage of Insulin Lecture Main Learning Points • Understand the insulin mechanism of action and its relationship to blood glucose • Understand the current usage of Insulin in Indonesia • Understand the different types of insulin, when to use insulin and the different insulin regiments • Understand the relationship between insulin dosage and blood glucose measurements Insulin Initiation and Monitoring Lecture: 30 minutes
  • 80. 80 Insulin remains the most efficacious glucose lowering agent Decrease in HbA1c: Potency of monotherapy HbA1c% Nathan et al., Diabetes Care 2009;32:193-203. IMS Full year 2011 Data. CIA World Factbook 29 67 92 Malaysia Thailand Vietnam Philippines 104 Bangladesh 161 Indonesia 248 Population Million People Mega Units Total Insulin Used 2,029 3,258 417 982 3,097 694 70 49 5 9 19 3 Insulin Usage per Capita Insulin Units / Capita …but Insulin usage is currently very low in Indonesia compared to its neighbouring countries
  • 81. 81 What is Insulin • After a meal carbohydrates are digested and enter the blood system, which transports them to the cells INSULIN is needed for glucose uptake and storage • Some cells (those of muscles and fat tissue) need assistance to have blood sugar enter into them and to be used for energy production • The liver needs assistance to start the process of storage of glucose in the form of glycogen …and our diabetes patients are not in good glycemic control DiabCare Indonesia 2008 illustrated the need for more intensive treatment to decrease FPG and PPG n: 1.823 patients with diabetes 208 144 100 140 0 20 40 60 80 100 120 140 160 180 200 220 mg/dl PPG (mg/dl)FPG (mg/dl) GlycemicControlLevel PERKENI GuidelinesDiabCare 2008 Source: Novo Nordisk Data on File
  • 82. 82 Insulin secretion is delayed and blunted in Type 2 Diabetes Adapted from: Polonsky KS, et al. N Engl J Med. 1996 Mar 21;334(12):777-783. Normal Type 2 diabetes Time (24 hours) 800 600 400 200 0 Insulin Secretion (pmol/min) Meal Meal Meal The goal of insulin therapy is to restore normal insulin secretion ‘Gap’ that needs to be covered How Insulin acts in the body Insulin Insulin binds to the insulin receptors on the cell membranes of the target cells in the liver, muscles and adipose tissue Liver Adipose Tissue Muscles • Inhibits glucose production • Promotes formation of glycogen and its storage • Promotes uptake and utilization of glucose • Promotes uptake of glucose • Suppresses lipolysis
  • 83. 83 …diabetes Patients will eventually fail on OAD’s 6.2% – upper limit of normal range MedianHbA1c(%) UKPDS 6 7 8 9 Years from randomisation Conventional* Glibenclamide Metformin Insulin 2 4 6 8 100 7.5 8.5 6.5 Recommended treatment target <7.0%† 8 6 7.5 7 6.5 Time (years) 0 2 3 4 51 ADOPT Metformin Glibenclamide Rosiglitazone *Diet initially then sulphonylureas, insulin and/or metformin if FPG>15 mmol/L; †ADA clinical practice recommendations. UKPDS 34, n=1704 UKPDS 34. Lancet 1998:352:854–65; Kahn et al (ADOPT). NEJM 2006;355(23):2427–43 Most people with type 2 diabetes will, in time, need insulin therapy Wright A et al. Diabetes Care 2002;25:330–6 (Patients treated with chlorpropramide) Years from start of UKPDS Patientsrequiring additionalinsulin(%) 0 10 20 30 40 50 60 1 2 3 4 5 6
  • 84. 84 Maintain blood glucose levels between 80-140 mg/dl: 1. By promoting uptake of glucose by target cells • subsequent breakdown into energy (glycolysis) • storage as glycogen (glycogenesis) 2. By inhibiting new glucose formation from non carbohydrate source (gluconeogenesis) or production of glucose by liver 3. By suppressing lipolysis (breakdown of fat) Objectives of Insulin Treatment Absolut Indication Type 1 Diabetes Relative Indication Patients who fail to reach target with OAD optimal dosage (3-6 months) Type 2 DM Outpatient with: Pregnancy not controlled with diet Infected Diabetes Feet High Blood Glucose Fluctuations Repeated History of Ketoacidosis History of Pankreotomi Besides the above, there are a number of conditions where insulin is required, e.g. chronic liver, kidney function interruption and high dosage steroid therapy Insulin Indications
  • 85. 85 Insulin can be initiated at any time… • Traditionally, insulin has been reserved as the last line of therapy… • …However, considering the benefits of normal glycemic status, Insulin can be initiated earlier. Inadequate Lifestyle + 1 OAD + 2 OAD + 3 OAD INITIATE INSULIN Adapted from Nathan DM, et al. Diabetes Care 2009; 31:193-203 ADA/EASD Guideline
  • 86. 86 Three Types of Insulin Schematic Representation OnlyGIR(mg/kg/min) Time (h) 0 4 8 12 16 20 24 BASAL INSULIN PRE-MIX INSULIN FAST-ACTING INSULIN Three Types of Insulin 1. Hompesch M. Diabetes Obes Metab 2006; 8:568; 2. Weyer et al. Diabetes Care 1997;10:1612–1614.; 3. 1. Heinemann et al. Diabetes Care. 1998;21:1910–4 Basal Insulin provides a steady concentration of insulin in the bloodstream over 24 hours. Initially, basal insulin should be given at 10 units per day at night time or in the morning1 Time (h) Premixed insulins contain a mixture of rapid-acting and intermediate-acting insulin in a fixed combination to provide coverage of prandial and basal insulin requirements2 Fast-acting insulins include single amino acid replacement that reduce their ability to self- associate into dimers and hexamers. This means that they are quickly absorbed into the bloodstream, following subcutaneous injection.3 FAST-ACTINGPRE-MIXBASAL GIR(mg/kg/min) 0 8 16 20 244 12 Time (h) GIR(mg/kg/min) 0 8 16 20 244 12 Time (h) GIR(mg/kg/min) 0 8 16 20 244 12
  • 87. 87 Basic Insulin Start Recommendation If Fasting Blood Glucose is elevated • Start with Basal Insulin If both Fasting and Prandial Blood Glucose are elevated • Start with Premix Insulin • OR add Basal Insulin to OAD • OR Start Basal/Bolus Therapy Source: ADA Guidelines Pharmacokinetics of the different Types of Insulin available in Indonesia Profile Type of Insulin Insulin Name Onset (hours) Peak (hours) Duration (hours) Fast-acting Analogue Insulin Insulin Aspart (NovoRapid) 0.2 – 0.5 0.5 - 2 3 - 5 Insulin Lispro (HumaLog) 0.2 – 0.5 0.5 - 2 2 - 4 Insulin Gluisine (Apidra) 0.2 – 0.5 0.5 - 2 1 – 2.5 Fast-acting Human Insulin ActRapid 0.5 – 1 0.5 - 1 3 – 6 Humulin R 0.5 – 1 0.5 - 1 3 - 6 Intermediate Human Insulin Insulatard 1.5 – 4 4 - 10 10 – 16 Humulin N 1.5 – 4 4 - 10 10 - 16 Long-acting Analogue Insulin Insulin Detemir (Levemir) 1 - 3 Up to 24 Insulin Glargine (Lantus) 1 - 3 Up to 24 Pre-mix Analogue Insulin Insulin Aspart (NovoMix) 0.2 – 0.5 1 - 4 10 -16 Insulin NPL (HumaLog) 0.2 – 0.5 1 - 4 10 -16 Pre-mix Human Insulin Mixtard 0.5 – 1 3 - 12 10 - 16 Humulin Mix 0.5 – 1 3 - 12 10 – 16 Adapted from Mooradian et al. Ann Intern Med 2006; 145: 125-34
  • 88. 88 Insulin Titration schemes Basal and Fast-Acting Insulin Fasting Blood Glucose Content (mg/dl) Basal Insulin Titration <70 mg/dl Reduce dosage with 2 units 70-130 mg/dl Maintain dosage 130-180 mg/dl Increase dosage 2 units per 3 days >180 mg/dl Increase dosage 4 units per 3 days Once titrated, continue to monitor HbA1c every 3 months BASAL INSULIN Subsequent pre-meal Glucose (mg/dl) Fast-acting Insulin Titration Start with 4 units / day Increase by 2 units every 3 days until target is reached When starting Fast-acting Insulin, secretagogues should be discontinued FAST- ACTING INSULIN Source: KONSENSUS: Insulin Treatment 2011 Insulin Treatment Optimization How to Optimize Treatment after Initiation Basal Insulin Only Usually with OAD Start with Basal Insulin 10u / daily with meal or before bedtime. Same injection time every day If glycemic target is not reached within 2-3 months, intensify Insulin treatment If glycemic target is not reached titrate according to Basal Titration Scheme Basal Insulin Only Usually with OAD Basal with Prandial Usually keep Metformin Premix Insulin Usually keep Metformin Basal Bolus Usually keep Metformin Add Prandial starting with 4u / day either once or twice-daily and titrate accordingly Switch to Premix twice-daily. Start with equal basal dose, but give 50% per injection and titrate accordingly Switch to Basal Bolus (3 daily prandial) start with 4u / day and titrate accordingly) Source: PERKENI Insulin Guidelines 2011
  • 89. 89 Primarily one type of Insulin device available in Indonesia • Disposable – disposed of once empty • Less teaching time required • Primarily plastic • Easy and Convenient for Patients Prefilled devices
  • 92. 92 Screening, Treatment and Evaluation of Complications Lecture: Screening, Treatment and Evaluation of Complications Lecture Main Learning Points • Understand the screening, diagnose and treatment options / refer for diabetes associated complications: • Nephropathy • Retinopathy • Neuropathy • Erectile Dysfunction • CVD • CAD
  • 93. 93 Recap: The goal of diabetes management is to secure optimal glycemic control to avoid complications Diabetic retinopathy Leading cause of blindness in working-age adults1 Diabetic nephropathy Leading cause of end-stage renal disease2 Cardiovascular disease Stroke 1.2- to 1.8-fold increase in stroke3 Diabetic neuropathy Leading cause of non-traumatic lower extremity amputations5 75% diabetic patients die from CV events4 1Fong DS, et al. Diabetes Care 2003;e 26 (Suppl.1):S99–S102. 2Molitch ME, et al. Diabetes Care 2003; 26 (Suppl.1):S94–S98. 3Kannel WB, et al. Am Heart J 1990; 120:672–676. 4Gray RP & Yudkin JS. Textbook of Diabetes 1997. 5Mayfield JA, et al. Diabetes Care 2003; 26 (Suppl.1):S78–S79. Microvascular Macrovascular Diabetic Foot Erectile Dysfunction The most secretive Complication of DM Recap: Risk of Complications increases as Hb1Ac increases Stratton IM et al. BMJ 2000;321:405–12 0 20 40 60 80 5 6 7 8 9 10 11 Myocardial infarction Microvascular disease Updated Mean HbA1c (%) Adjusted for age, sex, and ethnic group Incidenceper1.000 patient-years
  • 94. 94 Recap: It’s the diabetes-related complications – not the diabetes medicine - that carries the biggest cost to the society Cost increases with a factor of 22.5 if patients develop complications (ASKES Data) 900 40 0 100 200 300 400 500 600 700 800 900 US$ With ComplicationsWithout Complications Approximate Annual Cost / Diabetes Patient ASKES 2010 Unpublished data 22.5X Positive legacy effect of earlier glucose control Provides long-term reductions in both microvascular and macrovascular complications 15% p=0.01 24% p=0.001 13% p=0.007 9% p=0.04 Any diabetes endpoint Microvascular disease Myocardial infarction Death (any cause) 16% p=0.052 25% p=0.0099 6% p=0.44 12% p=0.03 RRR* at end of UKPDS RRR* at end F/U (median 8.5 years) RRR: relative risk reduction of intensive therapy over conventional therapy UKPDS 80. Holman et al. NEJM 2008; 359:1577-89.
  • 95. 95 Classification of Micro- and Macrovascular Complications Chronic complications of diabetes • Microvascular complications • Kidney – nephropathy » kidney failure • Eyes – retinopathy » blindness • Nerves – neuropathy » disability • Peripheral Arterial Diseases » disability • Erectile Dysfunction • Macrovascular complications • Heart – myocardial infarction • Brain – stroke • Atherosclerosis – myocardial infarction Microvascular Complications – an overview Retinopathy and blindness Nephropathy Neuropathy International Diabetes Federation. Diabetes Atlas 2006;111–2 Erectile Dysfunction
  • 96. 96 Diabetes Nephropathy Characteristics • Persistent albuminuria • Diabetic retinopathy • Hypertension • Decline in kidney function (about 12 ml/min/year) Diabetes Nephropathy Prevention and Treatment DCCT. Diabetes 1996;45:1289–98 Glycated haemoglobin (%) 5 8 12 0.0 0.4 0.8 0.6 0.2 111096 7 Probabilityof microalbuminuria • Maintain tight glycaemic and blood pressure control • Multifactorial disease management: • antihypertensive agents • good blood glucose control • control of dyslipidaemia • monitoring renal function • lifestyle changes, including smoking cessation and low-protein diet
  • 97. 97 Micro / Macro-albuminuria 24h: 30 - 299 mg/24h >300 mg/24h Random spot: 30 - 299 mcg/mg >300 mcg/mg Morning spot: 30 – 299 mcg/mg >300 mcg/mg Dipstick/overnight albumin: low sensitivity and specificity Micro Macro In 2 of 3 measurements Natural history of diabetic nephropathy . Functional GFR - (90-95%) Microalbuminuria, hypertension Proteinuria, nephrotic syndrome, GFR ¯ Urinary protein excretionGFR Urinaryproteinexcretion(mg/d) Years Glomerularfiltrationrate(GFR) (mL/min) 0 150 100 50 5 10 15 20 25 20 200 1000 5000 Incipient diabetic nephropathy Pre Overt diabetic nephropathy End-stage renal disease 1 2 3 4 5 Vora JP, et al. In: Johnson RJ, Feehally J, eds. Comprehensive Clinical Nephrology. New York: Mosby; 2000
  • 98. 98 Diabetes Retinopathy Non- Diabetic Retina Diabetic Maculopathy Proliferative Diabetic Retinopathy Treating Albuminuria • Use ACE-I or ARB in nonpregnant patiens with micro- or macroalbuminuria • Reduce protein intake to 0.8-1.0 g/kgBW/day in DM & early CKD; 0.8 g/kgBW/day in later CKD • If ACE-Is /ARBs/diuretics are given, monitor serum creatinine and potassium • When eGFR <60 ml/min/1.73m2, evaluate for CKD complications • Consider referral to experienced physician in kidney disease care Diabetes Care. 2012
  • 99. 99 Diabetes Retinopathy Risk Factors and Classification • Poor glycaemic and blood pressure control increase the risk of retinopathy • Five categories: • Mild Nonproliferative • Moderate Nonproliferative • Severe Nonproliferative • proliferative • advanced diabetic eye disease • maculopathy Chaturvedi et al. Diabetes Care 2001;24:284–9 London HbA1c (%) Retinopathyincidence(oddsratio) 4 6 9 0 5 10 875 35 30 25 20 15 10 DCCT HbA1c (%) 5.7 7.7 10.89.88.86.7 11.9 Diabetes Retinopathy Prevention and Treatment • Maintain tight glycaemic and blood pressure control • Regular eye examinations • Treat with laser photocoagulation and vitreoretinal surgery Klein et al. Ann Intern Med 1996;124:90–6
  • 100. 100 Diabetes Neuropathy Risk Factors and Common Types • Hyperglycaemia is the leading cause of diabetic neuropathy • Alcohol makes neuropathy worse • A number of clinical syndromes are recognisable Watkins et al. In: Diabetes and Its Management 2003. Pickup & Williams. In: Slide Atlas of Diabetes 2004 Pickup & Williams. In: Slide Atlas of Diabetes 2004 Symmetrical diffuse sensorimotor neuropathy Femoral neuropathy (amyotrophy) Other acute mononeuropathies Pressure palsies Sensory loss 0 → +++ Pain + → +++ Tendon reflexes N → ↓ Motor deficit 0 → + Sensory loss 0 → + Pain + → +++ Tendon reflexes ↓ → 0 Motor deficit + → +++ Sensory loss 0 → + Pain + → +++ Tendon reflexes N Motor deficit + → +++ Sensory loss + → +++ Pain + → ++ Tendon reflexes N Motor deficit + → +++ VIIII Truncal Ulnar Median Lateral popliteal Diabetes Neuropathy The Most Frequent Diabetes related Complication in Indonesia (and in the World…) Note: One patient can have more than one complication 6.7% 16.1%19.1%21.7% 41.9% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Neuropathy EyeCV Renal Foot Ulcer Frequency of complications A1Chieve Indonesia (2.240 patients) 8.7% 26.5% 33.4% 54.0% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Neuropathy Eye Renal Foot Ulcer Frequency of complications IDMPS Indonesia (715 patients)
  • 101. 101 Diabetic Foot Complications Diabetes Neuropathy Prevention and Treatment • Maintain tight glycaemic control to reduce the risk or progression of neuropathy • Exclude or treat contributory factors: • alcohol excess • vitamin B12 deficiency • uraemia • Offer pain relief based on the dominant symptoms DCCT. NEJM 1993;329:977–86 16 8 0 0 Percentageofcasesaffected p<0.001 12 4 Conventional therapy Intensified therapy 1 Time (years) 2 3 4 5
  • 102. 102 Erectile Dysfunction Definition ED is the inability to achieve and maintain an erection adequate for intercourse to the mutual satisfaction of the man and his partner. Remember, both partners in a relationship are affected Erectile Dysfunction Background • 35%-75% of men with diabetes will experience at least some degree of ED • Men with diabetes tend to develop erectile dysfunction 10 to 15 years earlier than men without diabetes. • Men with diabetes will have ED • 50%-60% in > 50 years old • 95% in >70 years old
  • 103. 103 Erectile Dysfunction Risk Factors  Risk Factors  Neuropathy  Peripheral vascular disease  Poor glycemic control  Diabetes duration and complications  Age and high BMI  Smoking doubles the risk Erectile Dysfunction Screening Rosen RC, Cappelleri JC, Smith MD, et al. Development and evaluation of an abridged, 5-item version of the International Index of Erectile Function (IIEF-5) as a diagnostic tool for erectile dysfunction. Int J Impot Res. 1999 Dec;11(6):319-26
  • 104. 104 MACRO VASCULAR COMPLICATION Erectile Dysfunction Treatment Options • Oral medications: Sildenafil (Viagra), Vardenafil (Levitra), Tadalafil (Cialis) • Urethral suppositories (MUSE) • Injection therapy: Caverject, Trimix, Bimix • Vacuum constriction device • Surgery • Sex therapy
  • 105. 105 Macrovascular Complications – an overview Stroke Cardiovascular/heart disease Peripheral vascular disease Cardiovascular Diseases Patients with Type 2 Diabetes at a increased risk of CVD • Risk of cardiovascular disease is greater in patients with diabetes than in those without • Having diabetes results in a similar risk of heart attack as a prior heart attack Incidence of myocardial infarction over 7 years Haffner et al. N Engl J Med 1998;339:229–34 With diabetes n=1059 Without diabetes n=1373 Patients(%)
  • 106. 106 Cardiovascular Diseases Risk for Myocardial infaction and stroke increases with progression to Type 2 Diabetes Adapted from Hu et al. Diabetes Care 2002; 25:1129-34 Relative risk for MI and stroke in women *Nurses’ Health Study (NHS) cohort comprised women only Relativerisk No diabetes during study Prior to diagnosis After diagnosis Diabetic at baseline Prevention of Cardiovascular Diseases Adapted from Stamler et al. Diabetes Care 1993;16:434–44 • Reduce risk factors for cardiovascular disease: • stop smoking • treat hypertension • treat hyperlipidaemia • improve glycaemic control • reduce weight in the obese • take regular exercise Number of risk factors Numberofdeathsper10,000patient-years Non-diabetic subjects Subjects with type 2 diabetes 0 1 2 3 0 20 40 60 80 100 120 140
  • 107. 107 Treatment of Cardiovascular Diseases Risk factors Hypertension SBP 130-139 or DPB 80-89 mmHg: lifestyle modification (DASH) for 3 months, if fails  pharmacological agents SBP ≥140 or DBP ≥90 mmHg: Lifestyle modification +pharmacological therapy Dyslipidemia Lifestyle modification + statins Antiplatelet agents* Aspirin and/or clopidogrel Smoking cessation Stop smoking, counseling CHD screening and treatment ACE-I and aspirin and statin (if not contraindicated) Diabetes Care 2012 *Depends on risk factors (???) Poor Control of CV Risk Factors in Diabetes (NHANES) Saydak SH et al. JAMA 2004 CV risk factors target Frequency • S-Cholesterol < 200 mg/dl (5.2 mmol/l) 52 % • BP < 130/80 mmHg 36 % • HbA1c < 7.0% 37 % • All three risk factors controlled 7 % • Unchanged CV risk factors from 1991 to 2000
  • 108. 108 STENO-2 STUDY The STENO2 Study – “a multifactorial approach to Type 2 Diabetes” New Engl J Med 2003; 383-93 New Engl J Med 2008; 358: 580-91 • 160 patients • Type 2 diabetes and microalbuminuria • Mean age 55 yrs, BMI 30 kg/m2; HbA1c 8.4 % • Randomized to • conventional therapy assigned to their GPs • or intensive care at Steno Diabetes Center
  • 109. 109 The STENO2 Study – Study Design Conventional treatment Intensive treatment Endpoint examinations Micro-vascular Macro-vascular 4 years 8 years 80 80 n=160 Advice to the Intensive Group • Food Advice • Cut down on animal fat • Have some kind of seafood every day • 5-6 vegetables and fruits every day • Exercise Advice • Enjoy physical performance > 150 min/week • Smoking cessation • Intensification of OHA and insulin • Treatment with ACE/ARB, Statin and baby aspirin
  • 110. 110 Patients in the Intensive Group had obtained better outcomes than patients in the Conventional Group… Intervention n=55 Standard n=38 Haemoglobin A1c (%) 7.7 8.0 F-s-total-cholesterol (mg/dl) 147 155 F-s-LDL-cholesterol (mg/dl) 71 77 F-s-triglycerides (mg/dl) 99 148 Systolic BP (mm Hg) 140 146 Diastolic BP (mm Hg) 74 73 Albumin excretion rate (mg/24h)* 69 75 Values are mean * median
  • 111. 111 The STENO2 Study Risk Reduction in Intensive Group Relative risk reduction after 8 years • Cardiovascular disease 53% • Diabetic Nephropathy 61% • Diabetic Retinopathy 58% • Autonomic Neuropathy 63% Screening, Treatment and Evaluation of Complications Lecture Main Learning PointsSummary • Complications should be screened for and treated according to guidelines • Routine follow up on treatment of complications should be performed • CVD complications are the mail cause of death among patients with diabetes • Risk of end-stage renal disease and blindness is significantly reduced by treatment of hyperglycemia and hypertension • Understand the treatment options for diabetes associated complications: • Nephropathy • Retinopathy • Neuropathy • Erectile Dysfunction • CVD • CAD
  • 112. 112 Assessment of Kidney function in Diabetes Mellitus type 2 GUIDELINES A.Annual Screening for albuminuria by : Albumin Excretion Rate (AER) – timed urine collection AER mg/ hour ug/min *in timed collection Microalbuminuria 30 - 300 20 - 200 Macroalbuminuria >300 >200 OR Albumin : Creatinine Ratio (ACR) – spot urine sample ACR Males (mg/mmol) Females (mg/mmol) Microalbuminuria 2,5 - 25 3,5 - 35 Macroalbuminuria >25 >35  If AER or ACR screening is positive for microalbuminuria : Perform additional ACR or AER measurements one to two times within 3 months. Microalbuminuria is confirmed if at least two or three tests (including the screening test) are positive.  If AER or ACR screening is positive for macroalbuminuria : Perform a 24 h urine collection for quantitation of protein excretion. AND B. Annual estimation of the Glomerular Filtration Rate (eGFR) eGFR Indicates <60 mL/min per 1,73 m2 At least moderate kidney dysfunction (stage 3 – 5 chronic kidney disease (CKD)) 60 – 90 mL/min per 1,73 m2 Mild kidney dysfunction (stage 2 CKD if albuminuria also present) Continue annual screening for albuminuria and eGFR in the event of negative screening tests. Reference : Chadban, et al. Nephrology 2010; 15, S146-S161
  • 113. 113 Simple Diabetes Foot Care Lecture: 30 minutes Simple Diabetes Foot Care Lecture Main Learning Points • Understand the risk factors for diabetic foot complications • Understand the steps for a simple diabetes foot examination • Understand the management of foot ulcers
  • 114. 114 From Theory to real-life – studies on foot care in RSCM 32% 26% 16% 26% RSCM 2003 Died Major Amputation and then Improved Discharge on their own will Improved without amputation 50% 14% 36% RSCM 2007 Died Amputation No Amputation Why foot care is important to diabetes management Have 15 – 40 fold higher risk of leg amputation than non diabetic Have a 15 % life time risk of developing foot ulcer Every 30 seconds a lower limb lost caused by diabetes 5-year suvival rate after major amputation < 50 % • 85% of diabetes-related amputations are happening in patients with foot ulcers • Early detection can prevent 40-85 % lower limb amputation Frykberg et al. J Foot Ankle Surg, 2000. IDF, International Working Group on Diabetic Foot 2007 Diabetes Patients
  • 115. 115 5 Cornerstones of diabetes foot care management Identification of risk factors Foot examination regularly Education (patients, providers and family) Treatment before Ulcer occurs Use appropriate footwear Risk Factors for diabetic foot ulceration Frykberg, Diabetic Microvascular Complications Today, May/June 2006 Intrinsic Factors Extrinsic Factors • Peripheral Neuropathy • Micro- and Macrovascular Diseases • Immunopahty • Structural Deformity • Limited Joint Mobility • Nephropathy • Age • Duration of Diabetes • Visual Acuity • Previous Ulceration • Minor mechanical trauma • Callus • Thermal Injury • Chemical Burns • Improper use of nail cutter • Smoking • Poor knowledge of diabetes • Psychological Factors • Alternative medication
  • 116. 116 Pathway to diabetic foot ulceration Reiber GE, Vileikyte, Boyko EJ et al. Causal pathways for incident lower–extremity ulcers in patients with from two settings. Diabetes Care 1999: 157-162 1% 30% 35%37% 63% 77%78% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Peripheral Neuropathy Peripheral Ischemia EdemaDeformityMinor Trauma Callus Infections Components leading to foot ulceration Intrinsic Factors Peripheral Neuropathy Autonomic SensoricMotoric Decreased Sweating Dry Skin Decreased Elasticity Fissure / Callus Ulcer • Loss of protective sensation • Decreased pain threshold • Lack of temperature sensation and proprioception Thermal Trauma in ‘bajaj’ Ill fitting Shoes
  • 117. 117 Intrinsic Factors Peripheral Arterial Disease (PAD) Risk Factors* • Hyperglycemia • Eleveted systolic blood pressure • hyperlipidemia • Smoking • Cardiovascular disease * UKPDS PAD • Correlated with atherosclerosis • A1c 1%  26 % PAD • More aggressive • Narrowing vessel lumen … obstructive • Distal tissue necrosis Intrinsic Factors Neuropathic Ulcers Influenced by: - Friction - Pressure
  • 118. 118 Intrinsic Factors Foot Deformities / Biomechanical Causes of Ulcers (Extrinsic Factors) Kyoto Foot Meeting 2010
  • 119. 119 Pathophysiology of diabetic foot Diabetes Mellitus Neuropathy Trauma Vascular Disease MOTOR Weakness Atrophy High Plantar Pressure Deformity Abnormal Stress Callus Formation Structural Deformity Cheiroarthropathy Impaired Response to Infection Diabetic Foot Ulcer AmputationAmputation AUTONOMIC Ischemia Diabetic Foot Disorders: A Clinical Practice Guideline (2006 Revision) SENSORY Loss of Protective Sensation Anhidrosis dry skin Sympathetic Tone MICROVASCULAR MACROVASCULAR Structural capillary BM thickening Functional AV Shunting Structural atherosclerosis Occlusive narrowing Ischemia Clinical Classification of diabetic foot (Edmond) Grade 1 Grade 2 Grade 3 Grade 4 Grade 5 Grade 6 Normal foot, no risk factors of neuropathy, ischemia, deformities No active ulcers, have ≥1 risk factors: neuropathy, ischemia, deformities, callus and swelling, nail deformities Skin breakdown; fisurre, blitser, ulcer Usually in plantar surface Foot develop infections, Discharge purulent, cellulitis, neuropathy and or ischemia Tissue necrosis with or with out intake foot, neuropathy, ischemia, neuroischemi, infection Unsalvageable foot, need major amputation, extensive necrosis, destroyed foot, severe infection
  • 120. 120 First 4 steps in the assessment Assessment Significant Finding Patient History - Previous foot ulceration - Previous amputation - Diabetic > 10 years - A1c > 7 % - Impaired vision - Neuropathic symptoms - Claudicatio Gross Inspection - Hammer toes - Claw toes - Halux valgus - Corn, callus, callus with ulcer, bunion - Prominent metatarsal head Dermatologic Examination - Dry skin - Absence of hair - Yellow or erythematous scale - Ulcer or healed ulcer - Interspace maceration - Moist - Unhealing ulceration Nail Deformities - Yellow, thickened nail - Ingrowing nail edge - Long or sharp nails 6 Steps for a complete Diabetes Foot Examination DIABETES FOOT EXAMINATION Patient History Gross Assess- ment Vascular Examination Screening for neuropathy Derma- tologic Examination Nail Defor- maties
  • 121. 121 Last 2 steps in the assessment Assessment Test Significant Finding Screening for Neuropathy - Semmes-Weinstein monofilamen 10 gram Lack of perception at one or more side - Tuning fork 128Hz Negative of vibration perception - Biothesiometer: Vibration perception Vibration perception threshold >25 volt Vascular Examination - Palpation of dorsalis pedis and tibialis posterior artery - Ankle Brachial Index - Color doppler • Decrease or absent pulse • ABI < 0.9 consistent with PAD ABI >1.2 0.9 – 1.2 <0.9 <0.6 Interpretation Rigid or calcified vessels or both Normal (or calcified) Ischemia Severe ischemia Risk Classification based on Foot Assessment Score Category Risk Profile Check-up Frequency 0 Low Risk • Pulsation ADP and ATP good • No deformities (hammer toe, claw toes, halux valgus, prominent metatarsal head) Once a year 1 Increased Risk • Pulsation ADP and ATP good • And/or deformities (hammer toe, claw toes, halux valgus, prominent metatarsal head) Once every 6 months 2 High Risk • ABI < 0,9 or ADP/ ATP not palpable • Deformities ( hammer toe, claw toes, halux valgus, , prominent metatarsal head Once every 3 months 3 Very High Risk • History of ulcer or amputation • Ulcer Once every 1-3 months
  • 122. 122 Intervention based on Risk Classification Score Category Intervention 0 Low Risk • Encourage extended knowledge on diabetes and foot care • Encourage self-care 1 Increased Risk • Inspect patient’s feet • Review need for vascular assessment • Evaluate footwear • Enhance foot care education 2 High Risk • Inspect patient's feet • Review need for vascular assessment • Evaluate provision and provide appropriate • Intensified foot care education • Specialist footwear and insoles • Skin and nail 3 Very High Risk • Multidisciplinary foot care team : • They should have unhindered access to suites for managing major wounds, • Urgent inpatient facilities • Antibiotic administration Prevention of Diabetes Foot DO Check your feet everyday Always wear footwear Check your footwear before wearing them Use shoes that fit Buy shoes in the afternoon Always use socks of cotton Wash your feet with soft soap and dry them Cut your nails in a flat way Check your feet regularly at the doctor Use lotion regularly at your skin DON’T’s Walk without shoes Use shoes that don’t fit Use socks that don’t fit to your foot Let your skin become dry Use sharp items to remove warts Smoke Use ring on finger Use high heels or shoes with sharp edges Over use of irritative lotion Use hot water to dip your feet
  • 123. 123 Wound Control1 1. Incision, drainage, debridement and necrotomy 2. Management of infections in tissue and bone 3. Exudate Management 4. Keep control of proliferation phase and infections Metabolic Control Infection Control Vascular Control Mechanic Control Wound Control Management of Foot Ulcers International Working Group on the Diabetic Foot 2007 1 2 3 4 5
  • 124. 124 Metabolic Control2 1. Hyperglycemia - Will inhibit process of wound recovery - Inhibit growth factor, collagen synthesis and fibroblast activities 2. Hypoalbuminemi 3. Hypertension 4. Decrease of heart and kidney function 5. Dyslipidemia 6. Anemia 7. Other diseases caused by diabetes Infection Control3 1. Need aggressive therapy 2. Usually there are no symptoms or signs of infection 3. External Infection: Positive gram bacteria 4. Internal Infection: Negative gram bacteria 5. Might need surgery
  • 125. 125 Use of Antibiotics3 Choice of antibiotics should be determined by: 1. Condition of the Infection: - Stage of infection and history of antibiotics - Bone infection, condition of blood vessels 2. Type of bacteria (sensitivity test) - Anarob, aerob, gram positive / gram negative 3. Condition of the patient - Allergy, heart and kidney function 4. Drug Profile - Safety, drug interactions, adverse events, frequency and dosage and price Vascular Control4 1. Neuroischemic Foot 2. Atherosclerosis can cause total block in the blood vessels 3. Decrease of blood flow to the wound 4. Critical Limb ischemia: Amputation Warning
  • 126. 126 Mechanic Control5 Principle: Reduce stress on the wound • Off loading • Might be bed rest • Non-weight bearing • Use of walker, wheel-chair or crutches • Use special shoes (‘half- shoes’) • Distribute the body weight to all surfaces of the foot Simple Diabetes Foot Care Lecture Main Learning PointsSummary • There are two risk factors for diabetic foot; intrinsic and extrinsic. • Check feet regularly to prevent ulcers. • Diabetes foot care management (Identification of risk factors, Foot examination regularly, treatment before ulcer occurs, use appropriate foot wear, education). • Management of foot ulcers (wound control, metabolic control, infection control, vascular control, mechanic control). • Understand the risk factors for diabetic foot complications • Understand the steps for a simple diabetes foot examination • Understand the management of foot ulcers