5. Introduction
The frequency of hyperglycemia potential contribution to
morbidity and mortality in hospitalized patients make
measurement of blood glucose mandatory in all patients
admitted to the hospital whether or not known diabetes
7. ADA Recommendations:
Diabetes Care in the Hospital
All patients with diabetes admitted to the hospital
should have
– Their diabetes clearly identified in the medical record
– An order for blood glucose monitoring, with results
available to the health care team
ADA. VIII. Diabetes Care in Specific Settings. Diabetes Care. 2011;34(suppl 1):S43.
8. Hyperglycemia Adversely Affects Outcomes
Diabetes increases the risk for disorders that predispose
individuals to hospitalization ,including cardiovascular
diseases, nephropathy, infection and lower-extremity
amputations.
9. Hyperglycemia Adversely Affects Outcomes
Hyperglycemia impacts
– Mortality
– Morbidity
– Rate of infections
– Length of hospital stay
18. Stress Hyperglycemia
On 2010 ADA proposed a threshold of blood
sugar 140 mg/dl in patient not known to have
diabetes
A1c eleveted should be measured above 6.5%
indicate preexisting diabetes in need for long term
follow up
20. Strategy of In-Hospital Management of Diabetes
Dose improving glycemic control improve
clinical outcomes for inpatients with
hyperglycemia ?
What glycemic target can be recommended in
different patients ?
21. Strategy of In-Hospital Management of Diabetes
What treatment options are available for achieving
optimal glycemic targets safely and effectively
in specific clinical situation?
22. Dose improving glycemic control improve clinical
outcomes for inpatients with hyperglycemia ?
23. Hyperglycemia and Hospital Mortality
Normoglycemia Known diabetes New hyperglycemia
35
30
*
Mortality (%)
25
20
*
15
10 *
5
0
Total Non-ICU ICU
*P<.01 compared with normoglycemia and known diabetes.
Umpierrez GE et al. J Clin Endocrinol Metab. 2002;87:978-982.
24. Hyperglycemia: An Independent Marker of
ICU Mortality
31%*
30
ICU Mortality
Mortality (%)
20
11%
10 10%
0
Normoglycemia Known New
Diabetes Hyperglycemia
Umpierrez et al. J Clin Endocrinol Metab 87:978, 2002 *P<0.01
25. • No doubt that hyperglycemia is associated
with poor clinical outcomes
• However, it does not mean that treatment of
hyperglycemia will improve clinical outcomes
27. DIGAMI Study
Diabetes, Insulin Glucose Infusion in Acute Myocardial Infarction(1997)
Acute MI With BG > 200 mg/dl
Intensive Insulin Treatment
IV Insulin For > 24 Hours
Four Insulin Injections/Day For > 3 Months
Reduced Risk of Mortality By:
28% Over 3.4 Years
51% in Those Not Previous Diagnosed
Malmberg BMJ 1997;314:1512
28. DIGAMI Study:
CVD Mortality Post-AMI
.7 All Subjects (N = 620) .7 Subjects at low CV risk and
.6 .6 w/ no prior insulin therapy
.5 .5 (N = 272)
.4 .4
.3 .3
.2 RRR=28% .2
RRR=51%
.1 P=.011 .1
0 0
P=.0004
0 1 2 3 4 5 0 1 2 3 4 5
Years of Follow-up Years of Follow-up
Standard treatment
Intensive management
Malmberg K et al. BMJ 314: 1512-1515, 1997
29. Van Den Berghe et al:
Intensive Insulin Therapy in Critically Ill Patients
------------------------------SICU---------------------------
Prospective randomized controlled study.
Enrolled 1548 SICU patients into 2 groups
Intensive therapy targeted glucose between 80-110 and
the conventional range was 180-200
Primary outcome was death in ICU which was 4.6
percent in the Intensive Glucose control group vs. 8.0
percent in Conventional glucose control group which
was statistically significant.
30. Van den Berghe et al 2
Intensive Insulin Therapy in the
Medical ICU
Prospective, randomized, controlled study of 1200
patients
Same authors and same conventional and intensive
parameters as the first study
Primary outcome was death in hospital which was
37.3% in the intensive group versus 40% in the
conventional group which was statistically
insignificant.
31. Wiener et al
Meta analysis of 34 randomized trials totaling 8432
patients.
Hospital mortality did not differ between tight vs.
conventional glucose control.
Tight glucose control was not associated with a
decreased risk for new dialysis, but was a associated
with a decreased risk of septicemia.
Tight glucose control was associated with an increased
risk of hypoglycemia.
32. GLUCONTROL
Prospective randomized control trial stopped early due
to adverse events in the tight BG control group.
Tight (80-110 mg/dL) vs Conventional(140-180 mg/dL)
glucose control.
Incidence of severe hypoglycemia (BG<40 mg/dL) was
significantly more frequent in patients assigned to tighter
control group. Risk of death was not increased by
hypoglycemia.
No difference in mortality 17% vs. 15% and the
conclusion of the authors was that there are no apparent
benefits of tight glucose control.
33. NICE-SUGAR
Intensive versus Conventional Glucose Control in Critically Ill
Patients
Randomized, prospective un-blinded clinical controlled trial
of 6104 patients.
34. Patients were randomized into one of 2 groups within 24
hours of admission to the ICU if they were expected to be
in the ICU for more than 3 days.
The 2 groups were intensive glucose control target (80-
108 mg/dL) or the conventional control target (180mg/dL
or less).
35.
36. NICE-SUGAR
.
In the intensive control group, control of blood glucose
was achieved with an insulin infusion.
In the conventional group, insulin was administered if the
blood glucose level exceeded 180mgdL.
37. NICE-SUGAR Results
.
829 patients(27.5%) died in the intensive control group
751(24.9%) in the conventional-control group which is
a difference of 2.6%.
There was no statistical difference between surgical
vs. medical ICU patients
.
38. NICE-SUGAR
Results
Severe hypoglycemia(<40mg/dL) was recorded in 6.8%
of patients in the intensive control group, vs. 0.5%
in the conventional group.
39. These conflecting findinges have called to question the
benefit of tight control and highlight in the risk for severe
hyperglycemia
so
41. ADA/AACE Target Glucose Levels in
ICU Patients
ICU setting:
– Insulin infusion should be used to control hyperglycemia
– Starting threshold of no higher than 180 mg/dl
– Once IV insulin is started, the glucose level should be maintained
between 140 and 180 mg/dl
– Lower glucose targets (110-140 mg/dl) may be appropriate in
selected patients
– Targets <110 mg/dL are not recommended
Not recommended Acceptable Recommended Not recommended
< 110 110-140 140-180 >180
ADA/AACE Inpatient Task Force
Endocrine Practice 2009;15;1-17
42. AACE-ADA Consensus Statement on
Inpatient Glycemic Control: ICU
Glucose target
140-180mg/dl
Moghissi E et al., Diabetes Care 2009;32:1344; Moghissi E et
al., Endocrine Practice 2009;15:353
43. AACE-ADA Consensus Statement on
Inpatient Glycemic Control: ICU
• Lower target acceptable
• ( 110-140 mg/dl )
Moghissi E et al., Diabetes Care 2009;32:1344; Moghissi E et
al., Endocrine Practice 2009;15:353
44. AACE-ADA Consensus Statement on
Inpatient Glycemic Control: ICU
• Tighter targets ( <110 mg/dl ) not safe;
• >180 mg/dl not acceptable.
Moghissi E et al., Diabetes Care 2009;32:1344; Moghissi E et
al., Endocrine Practice 2009;15:353
45. ADA/AACE Target Glucose Levels in
Non-ICU Patients
Non-ICU setting:
– Pre-meal glucose targets <140 mg/dL
– Random BG <180 mg/dL
– To avoid hypoglycemia, reassess insulin regimen if BG levels fall
below 100 mg/dL
– Occasional patients may be maintained with a glucose range
below or above these cut-points
Hypoglycemia= BG < 70 mg/dl
Severe hypoglycemia= BG < 40 mg/dl
ADA/AACE Inpatient Task Force
Endocrine Practice 2009;15:1-17
46. Achieving Tight Glycemic Targets
.
What treatment options are available for achieving
optimal glycemic targets safely and effectively in specific
clinical situation?
48. Oral Antidiabetes Agents in the Hospital
Oral agents can be continued in stable patients with
normal nutritional intake, normal blood glucose levels,
and stable renal and cardiac function.
However, there are several potential disadvantages to
using these medications in hospital patients:
50. Disadvantages of insulin secretagogues
(e.g. sulfonylureas and meglitinides such as glyburide,
glypizide, repaglinide, etc.):
• Hypoglycemia if caloric intake is reduced
• Some are long-acting (hypoglycemia may be prolonged)
51. Disadvantages of Metformin:
• Lactic acidosis can occur when used in the setting of
renal dysfunction, circulatory compromise, or hypoxemia
• Slow onset of action
• GI complications: Nausea, diarrhea
52. Insulin
only
The most powerful agent we
have
to control blood glucose
53. Conclusions
Inhospital glycemic control is now recognized as a
patient safety issue
BG target 140 mg/dL-180 mg/dL
Safe and Effective Protocols can be implemented
institutionally to attain goals with acceptable
hypoglycemia
American Diabetes Association. Diabetes Care. 2006;29:S4-S42.
57. IV Insulin Therapy: Recommended Uses
Best method to achieve quick glycemic control
Continuous Variable Rate IV Insulin Drip
Major Surgery, NPO, Unstable, MI, DKA,
Hyperglycemia, Steroids, Gastroparesis,
Delivery, etc
Basal / Bolus Therapy when eating
Bode et al. Endocr Pract. 2004;10(suppl 2):71-80
58. Patient with an Acute MI
53 yo male with DM 2 on SU, Metformin and
Glitazone presents with an acute MI
BG random is 220 mg/dl
What do you recommend for glucose control?
1. Sliding scale rapid analog?
2. Basal Bolus insulin therapy?
3. IV insulin drip?
59. Patient with an Acute MI
For acute MI with elevated glucose, you can give in
type 2’s IV variable rate insulin infusion in all
persons with elevated glucose
60. If you order an IV insulin drip ;
1- What dilution of IV insulin?
2- How often do you check the glucose?
62. Continuous Variable Rate IV Insulin Drip
Mix Drip with 125 units Regular Insulin into
250 cc NS
Starting Rate Units / hour = (BG – 60) x 0.02
where BG is current Blood Glucose
and 0.02 is the multiplier
Check glucose every hour and adjust drip
Adjust Multiplier to keep in desired glucose
target range
63. Continuous Variable Rate IV Insulin Drip
Adjust Multiplier (initially 0.02) to obtain glucose in
target range 100 to 140 mg/dL
If BG > 140 mg/dL, increase by 0.01
If BG < 100 mg/dL, decrease by 0.01
If BG 100 to 140 mg/dL, no change in Multiplier
If BG is < 80 mg/dL, Give D50 cc = (100 – BG) x 0.4
Give continuous rate of Glucose in IVF’s
Once eating, continue drip till 2 hours post SQ insulin
64. The default insulin drip column
< 100 off
100-109 0.5 Check BG every 1 hr and adjust
rate
110-129 1.0
130-149 1.5
150-169 2.0
170-189 2.5
190-209 3.0
210-254 4.0
255-299 5.0 etc.
65. Converting to SC insulin
If More than 0.5 u/hr IV insulin required with
normal BG, start long-acting insulin (glargine)
Must start SC insulin at least 2 hours before
stopping IV insulin
Some centers start long-acting insulin on initiation
of IV insulin or the night before stopping the drip
66. How to Initiate
Starting dose = 0.4 to 0.5 x weight in kilograms
Bolus dose (aspart/lispro) = 20% of starting dose at
each meal
Basal dose (glargine) = 40% of starting dose given
at bedtime or anytime
Correction bolus = (BG - 100)/ Correction Factor,
where CF = 1700/total daily dose
67. Starting dose = 0.45 x wgt. in kg
Wt. is 100 kg; 0.45 x 100 = 45 units
Bolus dose (aspart / lispro) = 20% of starting dose
at each meal; 0.2 x 45 = 9 units ac (tid)
Basal dose (glargine) = 40% of starting dose at HS;
0.4 x 45 = 18 units at HS
Correction bolus = (BG - 100)/ CF, where
CF = 1700/total daily dose; CF = 40 or 3000 / wgt kg
69. Calculating Initial MDI* Doses for Insulin-naïve
Patients
Starting dose = 0.5 × weight in kg
Basal dose = 40%-50% Total prandial dose = 50%-
of starting dose at bedtime 60% of starting dose, 1/3 at
each meal*
Do not skip correction dose even if
no food eaten
*Give after meals as rapid-acting analog if food intake is in doubt Adjust upwards daily by adding 50%
*MDI = Multiple daily injection of correction doses to basal and bolus
Thompson et al. Diabetes Spectrum. 2005;18:20-27. doses
70. Calculating Initial MDI* Dose: Example
Assume 100-kg person with moderate insulin resistance
Starting dose = 0.5 × 100 kg =50U
Basal dose = Prandial doses =
0.4–0.5 x 50 U = 20-25 U at (0.5–0.6 x 50) = 25-30 U ÷ 3 or 8–
bedtime 10 U at each meal*
Give correction dose
*Give after meals as rapid-acting analog if food intake is in doubt
*MDI = Multiple daily injection
Thompson et al. Diabetes Spectrum. 2005;18:20-27.
72. What to do depends on several questions
Who is the patient?
Which is the outpatient regimen?
How well is it controlling glucose
What is the current glucose
When is the patient to eat?
Why is the patient admitted
73. Hyperglycemia & Patients on General Medical Wards
Absolute risk of adverse outcome (death or prolonged stay) increased
15% per 18-mg/dL increase in glucose levels
35
30
Mortality (%)
25
20 N=433 patients with
COPD Exacerbations
15
10
5
0
< 109 109-125 126-162 >163
mg/dL
Baker EH et al. Thorax. 2006;61:284-289.
mg/dL mg/dL mg/dL
74. New AACE-ADA Consensus Statement on Inpatient
Glycemic Control
Moghissi E et al. Diabetes Care 2009, Endocrine Practice 2009
Non–ICU
Setting - Most patients:
• pre-meal BG <140 mg/dL
• random BG <180 mg/dL
- More stringent targets may be appropriate in stable
patients
- Scheduled SQ insulin with basal- nutritional-
correction preferred
75.
76.
77. RABBIT 2 Trial
Prospective randomized trial of 130 insulin
naïve T2DM non-ICU inpatients
Admission blood glucose b/w 140-400 mg/dl
Basal- bolus insulin with glargine and glulisine
vs Regular insulin SS
88. Common Features Increasing Risk of Hypoglycemia
in an Inpatient Setting
• Advanced age
• Decreased oral intake
• Chronic renal failure
• Liver disease
• Changes in clinical status or medications
Beta-blockers ,Corticosteroids
89. A person with diabetes on tube feedings
What is the best insulin treatment for a DM
patient on tube feedings? (BG 150 to 300 mg/dl)
If unstable, first give IV insulin and determine the
requirement over 24 hours and then change to
SC basal (glargine Q 12 hours) with supplemental
rapid acting every 4 to 6 hours.
Can also use NPH Q 8 hours or regular Q 6 hours
as the basal
90. A person with diabetes on TPN
What is the best insulin treatment for a DM
patient on TPN? (BG 150 to 300 mg/dl)
If unstable, first give IV insulin variable drip and
determine the requirement over 24 hours and
then add all the insulin to the TPN bag.
Continue to supplement every 4 to 6 hours with SC
rapid acting insulin using BG – 100 / CF where CF
is equal to 3000 divided by weight in kg. On
average, CF = ~ 30 to 40
91. DM 1 patient in DKA (ph 7.0; BG 400
mg/dl: weight 80 kg)
When do you start potassium and how much?
When do you start dextrose and how much?
preference is 2 liters saline followed by D50.45
saline with 40 meq KCL/liter at
250 ml/hour. Monitor electrolytes Q 4 to 8
hours.
92. Protocol for Insulin in Hospitalized Patient
Treat Any Patient With BG >140 mg/dl With Insulin
– Treat Any BG >140 mg/dl with Rapid-acting Insulin
(BG-100) / (3000 / wt kg) or 1700 / total daily insulin
– Treat Any Recurrent BG >180 mg/dl with IV Insulin if
failing SC therapy or >140 mg/dl if NPO, acute MI,
perioperative, ICU, or >100 mg/dl if pregnant
If More than 0.5 u/hr IV Insulin Required with Normal BG
Start Long Acting Insulin
93. Protocol for Insulin in Hospitalized Patient
Daily Total: Pre-Admission or Weight (#) x 0.2 u
– 40 % as (Basal)
– 60% as Rapid-acting insulin (Bolus)
• Give in Proportion to Meal’s CHO Eaten
BG >140 mg/dl: (BG-100) / CF
CF = 1700 / Total Daily Insulin or 3000 / wgt kg
Do Not Use Sliding Scale As Only Diabetes
Management
96. Recommendations:
Diabetes Care in the Hospital (2)
Goals for blood glucose levels
– Critically ill patients: 140-180 mg/dl
(10 mmol/l) (A)
– More stringent goals, such as 110-140 mg/dl (6.1-7.8 mmol/l) may be
appropriate for selected patients, if achievable without significant
hypoglycemia (C)
– Non-critically ill patients: base goals on glycemic control, severe
comorbidities (E)
ADA. VIII. Diabetes Care in Specific Settings. Diabetes Care. 2011;34(suppl 1):S43.
97. Recommendations:
Diabetes Care in the Hospital (3)
Scheduled subcutaneous insulin with basal,
nutritional, correction components (C)
Use correction dose or “supplemental insulin” to
correct premeal hyperglycemia in addition to
scheduled prandial and basal insulin (E)
Initiate glucose monitoring in any patients not
known to be diabetic who receives therapy
associated with high risk for hyperglycemia (B)
ADA. VIII. Diabetes Care in Specific Settings. Diabetes Care. 2011;34(suppl 1):S43.
98. Recommendations:
Diabetes Care in the Hospital (4)
A hypoglycemia management protocol should be
adopted and implemented by each hospital or hospital
system
– Establish a plan for treating hypoglycemia for each patient;
document episodes of hypoglycemia in medical record and
track (E)
Obtain A1C for all patients if results within previous 2-3
months unavailable (E)
Patients with hyperglycemia who do not have a
diagnosis of diabetes should have appropriate plans
for follow-up testing and care documented at discharge
(E)
ADA. VIII. Diabetes Care in Specific Settings. Diabetes Care. 2011;34(suppl 1):S43.
99. What to do depends on several questions
Who How well is When is the
is the it patient to
patient? controlling eat?
Which is glucose? What is the Why is the
• Type 1? the • A1c 6.5%? current • NPO? patient
• Type 2? outpatient • A1c 9.5%? glucose? • Full diet? admitted?
regimen?
• Orals? • BG=142? • Sepsis?
• Insulin? • BG=442? • A-Fib?
• Combo?
100. Intervention Studies
Showing Benefits Showing No Benefits
• Van den Bergh-SICU • DIGAMI-2
• Van den Bergh-MICU • CREATE-ECLA
• DIGAMI-1
• VISEP trial
• GIST-UK
• Krinsley study
• Intra-operative cardiac
• Furnary data surgery study
