Diabetes for nurses

1. DIABETES MELLITUS
IN RENAL COMPLICATIONS
นพ.กมล โฆษิตรังสิกุล
อายุรแพทย์โรคไต
โรงพยาบาลมหาราชนครศรีธรรมราช

2. WHAT IS DIABETES ?
A chronic metabolic disorder causing elevation of
blood glucose and specific & nonspecific
complications

3. INTRODUCTION
Between 1985 and 2010, the worldwide prevalence of
DM has risen almost 10-fold, from 30 million to 285
million cases.
In the United States, DM prevalence in 2010 is
estimated at 26 million, or 8.4% of the population.
A significant portion of persons with DM are
undiagnosed.

4. THE BURDEN OF DM IN THAILAND
Prevalence of DM in Thai adults (age > 35 years) was
9.6%
4.8% Known DM, 4.8% newly Dx DM
2.4 million people have diabetes
Fair access to diabetes medications
Diabetes Care 2003; 26: 2758-63

6. INCIDENT COUNTS & ADJUSTED
RATES OF ESRD
2012 USRDS annual Data Report

7. CAUSE OF CKD IN THAI RRT 2003
DM, 1348,
34%
HT, 1043, 26%
CGN, 558,
14%
Other, 448,
11%
Unknown,
613, 15%

8. DIAGNOSIS OF DM
Criteria for the diagnosis of DM include one of the following:"
Hemoglobin A1c >6.5%
Fasting plasma glucose ≥7.0 mmol/L (≥126 mg/dL)
Symptoms of diabetes plus a random blood glucose
concentration ≥11.1 mmol/L (≥200 mg/dL)
2-h plasma glucose ≥11.1 mmol/L (≥200 mg/dL) during
a 75-g oral glucose tolerance test.
ADA 2010

9. DIAGNOSIS
Categories of increased risk for DM"
Impaired fasting glucose (IFG) for a fasting plasma
glucose level of 5.6–6.9 mmol/L (100–125 mg/dL)
Impaired glucose tolerance (IGT) for plasma glucose
levels of 7.8–11.1 mmol/L (140–199 mg/dL) 2 h after
a 75-g oral glucose load
HbA1C 5.7-6.4%

10. การแปลผล FPG
Normal FG IFG Provisional DM
100 126 mg/dL

11. OGTT
การทดสอบความทนกลูโคส
เป็นวิธีทดสอบการทํางานของβ-cell ของตับอ่อน ในการหลั่ง
insulin หลังกินกลูโคสในปริมาณสูง (75 g)
คนปกติสามารถลดระดับนํ้าตาลลงมาได้ภายใน เวลา 2 ชั่วโมง
ผู้ที่มีการหลั่งinsulin บกพร่องหรือเป็นโรค เบาหวาน จะต้องใช้
เวลาในการลดระดับนํ้าตาลนานกว่า 2 ชั่วโมง

12. 75 gm glucose

13. ข้อบ่งชี้ การส่งตรวจ OGTT
1. เพื่อตรวจยืนยันการวินิจฉัยโรคเบาหวานในกรณีที่การตรวจ FPG ให้
ผลไม่ชัดเจน(IFG)
2. FPG ให้ผลปกติแต่มีความสงสัยว่าจะเป็นโรคเช่น
2.1 มีอาการทางคลินิกของโรคเบาหวาน เช่น retinopathy,
neuropathy, peripheral arterial disease
2.2 กลุ่มที่มีแนวโน้มอาจจะเป็นโรคเบาหวานได้ มากกว่าผู้อื่น (high
risk group)

14. การแปลผล OGTT
Normal GT Provisional DM
140 200 mg/dL
75 gm glucose then 2 hour plasma glucose
Impaired GT
(DIABETES CARE 2007; 30)

15. !
SCREENING
Screening with a fasting plasma glucose level
is recommended every 3 years for individuals
over the age of 45, as well as for younger
individuals who are overweight
(body mass index ≥25 kg/m2) and have one
or more additional risk factors.

16. ADDITIONAL RISK FACTORS
Physical inactivity
First-degree relatives with diabetes
Members of high-risk ethnic population(eg. African American,
Latino, Native American, Asian American, Pacific Islander)
Women who delivered a body weighing 9 Ib (4 kg) or were
diagnosed with GDM
Hypertension (140/90 mHg or on therapy for hypertension)

17. ADDITIONAL RISK FACTORS
HDL < 35 mg/dL and/or a triglyceride level > 250 mg/dL
Women with polycystic ovary syndrome
A1C 5.7 %, IGT, IFG on previous testing
Other clinical conditions associated with insulin
resistance (eg. severe obesity, acanthuses nigricans)
History of CVD

18. ADA CLASSIFICATION OF DIABETES
Type 1 Diabetes Mellitus
Type 2 Diabetes Mellitus
Other specific types
Gestational Diabetes Mellitus

19. DIABETES MELLITUS
Type 1 Diabetes (5-10%)
Juvenile Onset, IDDM, type I
Auto-immune disease
Pancrease is unable to produce insulin (Beta cell destruction)
Required insulin for survival
Generally diagnosed from birth to age 30, highest incidence age 12-18

20. DIABETES MELLITUS
Type 2 Diabetes (90-95%)
Adult onset, NIDDM, type II
Variable degree of insulin deficiency coupled with
insulin resistance
Disorder associated with obesity and the ageing process
Generally diagnosed after age 40

21. DIABETES MELLITUS
Gestational Diabetes Mellitus (GDM)
Hyperglycemia first diagnosed in pregnancy
Diagnosis made by OGTT

22. DIABETES MELLITUS
Other specific types
Maturity-Onset Diabetes of the Young (MODY)(<1%)
Pancreatic disease
Drug
etc.

23. ETIOLOGY OF DIABETES

24. Adapted from DeFronzo RA.Diabets 1988;37:667-87

25. COMPLICATION OF DIABETES
Acute complication: Hyperglycemic crisis
Diabetic Keto-Acidosis (DKA)
Hyperglycemic Hyperosmolar State (HHS)
Long term complications
Microvascular
Macrovascular

26. ACUTE COMPLICATION
Type I DM
DKA
Rapid deep breathing
Abdominal pain
Nuasea/Vomiting
Fruity odor of ketone
Type 2 DM
HHS
Weight loss
Seizure
Polyuria
Polydipsia
Drowsy
Coma

27. ACUTE COMPLICATION
DKA HHS
DM Type1 Type2
Glucose(mg/dl) >250 >600
pH <7.3 >7.3
Serum HCO3(mEq/L) <15 >20
BUN (mg/dl) <25 >30
S. Osmolality <320 >320
Ketones > 3+ - / small

28. CHRONIC COMPLICATIONS OF DM
Ophthalmologic: nonproliferative or proliferative
diabetic retinopathy, macular edema, rubeosis of iris,
glaucoma, cataracts
Neurologic: distal symmetric polyneuropathy,
polyradiculopathy, mono-neuropathy, autonomic
neuropathy

29. CHRONIC COMPLICATIONS OF DM
Gastrointestinal: gastroparesis, diarrhea,
constipation
Genitourinary: cystopathy, erectile dysfunction,
female sexual dysfunction, vaginal candidiasis

30. CHRONIC COMPLICATIONS OF DM
Cardiovascular: coronary artery disease, congestive
heart failure, peripheral vascular disease, stroke
Lower extremity: foot deformity (hammer toe, claw
toe, Charcot foot), ulceration, amputation
Dental: Periodontal disease

31. CHRONIC COMPLICATIONS OF DM
Dermatologic: Infections (folliculitis, furunculosis,
cellulitis), necrobiosis, poor healing, ulcers, gangrene

32. CHRONIC COMPLICATIONS OF DM
Renal: proteinuria, end-stage renal disease (ESRD),
type IV renal tubular acidosis

33. CHRONIC COMPLICATIONS
cataract
retinopathy
!
!
proteinuria
!
!
neuropathy
!
!
!
Arthero
sclerosis
!
Blindness!
!!
Kidney
failure!
!
Amputation!
!
MI!
!
Stroke!

35. CAUSES OF MORTALITY IN DIABETES
32!
Heart Disease
Cerebrovascular
Disease
Other
Pneumonia/
InfluenzaMalignant
Neoplasms
Diabetes
Geiss LS, et al. In: Diabetes in America. 2nd ed. NIH Publication No. 95-1468. 1995:233-257.
Causes of Mortality in Patients With
Diabetes
10%
13%
13%
4% 5%
55%
Geiss LS, et al :Diabetes in America 2 nd ed, NIH publication No.95-1468. 1995:233-257

36. CLINICAL PROGRESSION
Stage Onset Designation Kidney change
1 เมื่อวินิจฉัย Hyperfunction GFR ↑
2 2-3 ปี Silent stage GFR ↑ ,Thick GBM
3 >5 ปี Incipient stage GRF ↑ or
Microalbuminuria
4 >10 ปี Overt DN GFR or ↓
Clinical proteinuria
5 >15 ปี ESRD GFR < 10 ml/min

37. DEFINITION IN ALBUMIN EXCRETION
.
Random** 24 hr Urine Timed
(microgram/min)
Normal <30 mg/g <30 mg/24h <20
Microalbuminuria 30-300 mg/g 30-300 mg/24h 20-200
Macroalbuminuria >300 mg/g >300 mg/24h >200
Diabetes Care 28, Supple 1, Jan 1998

38. No nephropathy
Microalbuminuria
Macroalbuminuria
Rising Cr, RRT
0.3%
2.8%
0.1%
0.1%
1.4%/ years
2.3%
3.0%
19.2%
2.0% / years
4.6%
DEATH
UKPDS 64: Kidney Int 2003; 63:225-232

39. GLYCEMIC GOAL IN ADULT

40. GLYCEMIC GOAL IN ADULT
DIABETES(CARE,(VOLUME(35,(SUPPLEMENT(1,(JANUARY(2012!

42. Monotherapy
Insulin therapy
Combination oral therapy
Lifestyle modification
Expected HbA1c
(time allotted)
1% (3 months)
1 to 2%
(1 3 months)
1 to 2% fall per
additional OHA
(1 3 months)
Unlimited
T2DM treatment strategies
Adapted from Bergenstal RM. In: De Fronzo RA, et al (eds). International Textbook of Diabetes
Mellitus. 3rd ed. Chichester, New York: John Wiley & Sons; 2004:995 1015.

43. PRIMARY SITE OF ACTION
48!
Glucose
Adipose tissue
Gut
Stomach
Liver
Sulphonylureas and
glinides
TZDs
Biguanides
Muscle
Pancreas
Insulin
Adapted from Kobayashi M. Diabetes Obes Metab 1999; 1 (Suppl 1): S32–40;
Nattrass M et al. Baillieres Best Pract Res Clin Endocrinol Metab 1999; 13: 309–29.
α-glucosidase inhibitors
Primary sites of action of oral
antidiabetic agents
incretin

45. METFORMIN
Decrease hepatic glucose production
Mechanism: Unclear, Activating the AMP-activated
protein kinase (AMPK)

46. METFORMIN
J. Clin. Invest. 2001;108(8): 1167-74.

47. CLINICAL ADVANTAGES OF METFORMIN
1.Does not cause weight gain
2.Does not cause hypoglycaemia
3.Improve lipid profile
Decrease plasma triglyceride 10-20%
Decrease plasma cholesterol 5-10%
Small increases in HDL-C Levels
4.Decrease plasma insulin levels

48. ADVERSE EFFECTS OF METFORMIN
1.Gastrointestinal 10-30%
diarrhea, nausea, abdominal discomfort
anorexia, metalic taste
2.Impaired absorption of Vit B12 and folate
3.Lactic acidosis

49. CONTRAINDICATION & CAUTION
FOR THE USE OF METFORMIN
Renal impairment :
Cr > 1.5 mg/dL ; men
Cr >1.4 mg/dL ; women
Cardiac or respiratory
insuffiency
History of lactic acidosis
Severe infection
Liver disease
Alcohol abuse
Use of intravenous radio
contrast agents

50. METFORMIN USE BASED ON GFR
DIABETES CARE, VOLUME 34, JUNE 2011

51. SULFONYL UREA
Pancreatic action
Stimulation of insulin secretion by closing ATP-
dependent potassium channels causing calcium
influx

52. INSULIN SECRETAGOGUES
Drug ! Dose !T 1/2 !Metabolites !Excretion"
! ! !(mg/d) ! (h)"
Chlorpropamide 100 - 500 36 Active or Kidney
unchanged
Glipizide 2.5 - 30 2-4 Inactive Kidney 80%
Bile 20 %
Gliburide 1.25 - 20 10 Inactive & Kidney 50%
weakly active Bile 50 %
Glimepiride 1 - 8 9 Inactive & Kidney 60%
weakly active Bile 40 %
Repaglinide 1.5 - 6 1 Inactive Bile

53. CONTRAINDICATION TO SULFONYL UREA
1. IDDM
2. post-pancreatectomy
3.During acute diabetic complication
4.During stress, infection or major operation
5.Renal impairment
6.During gestation?
7.Adverse drug reaction

54. HYPOGLYCAEMIA FROM SULFONYLUREAS
Risk factors
1.Age > 70 yr
2.Poor nutrition
3.Alcohol intake
4.Impaired renal function
5.Drug interactions

55. THIAZOLIDINE DIONE
Ligand for PPAR ɣ , a nuclear receptor transcription factor
regulates many gene expression involved in CHO and lipid
metabolism
Specific mechanism: unclear
⬆️ insulin-mediated glucose uptake by skeleton muscle
⬇️ lipolysis and enhance adipocyte differentiation
indirect effect mediated through adipokines

56. ADVERSE EVENT OF TZD
1.Edema: generally dose related, more commonly observed when
combination with SU, Insulin
2.Weight gain: up to 8 kg
3.Anemia: Hct drop around 3%
4.Congestive heart failure
5.Macular edema
6.Bone fractures
7.Exacerbate Grave’s opthalmopathy

57. INSULIN
Types Examples
Bolus (Meal) Insulin
Rapid-acting lispro, aspart, glulisine
Short-acting Regular
Basal (Background) Insulin
Intermediate-acting NPH, Lente
Long-acting Glargine
Pre-Mixed Insulin
NPH/Regular 70/30, 50/50
NPL/Lispro Mix 75/25
NPA/Aspart Mix 70/30

58. INSULIN ACTION
76!
Insulin Action:
Comparison of New Insulin Analogs
0
20
40
60
80
100
120
140
0 2 4 6 8 10 12 14 16
Regular
Rapid (Lispro, Aspart)
InsulinLevel(µU/ml)
Hours
Intermediate (NPH)
Long ( Detemir,Glargine)

59. INSULIN ACTION
Comparison of Human insulins and insulin analogues
Insulin Onset of Duration of
Preparations Action Peak Action Action
Lispro/Aspart 5-15 min 1-2 hr 4-6 hr
Human Regular 30-60 min 2-4 hr 6-10 hr
Human NPH/Lente 1-2 hr 4-8 hr 10-20 hr
Glargine/Detrimir 1-2 hr Flat ~24 hr
Endocrinol Metab Clin North Am 2001;30:944

60. Dyslipidemia

61. DM#Type#II#&#CVD,#CKD,#
CVD#with#age#>#40#yr##
with#TOD#
#or#>#1#risk##
#
#
LDL>C#goal#<#70#mg/dl !
Non#HDL>C#<100#mg/dl##
#Apo#B#<#80#mg/dl#
!
!
!
All!DM!type!II!!patients!
!
LDL0C<100!mg/dl!
Non!HDL0C!<130!mg/dl!!
!Apo!B!<!100!mg/dl!
!
European)Heart)Journal)(2011))32,)1769–1818)

62. !
Mod!to!severe!CKD!
LDL.C!target!70!mg/dl!
!
Expert!:!Sta;n!may!slow!
rate!of!kidney!func;on!loss!
!
CKD$=$CAD$Risk$equivalent$
$
LDL4C$lowering$is$useful$
$
European)Heart)Journal)(2011))32,)1769–1818)

68. FOLLOW UP AFTER START ACEI/ARB