ueda2012 ada diabetes hospital management-d.diaa

1. In-Hospital Management of Diabetes

4. ‫مصر‬ ‫يا‬ ‫يحميك‬ ‫هللا‬

5. 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
Introduction

6. STANDARDS OF MEDICAL CARE
IN DIABETES—2011

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. Diabetes increases the risk for disorders that predispose
individuals to hospitalization ,including cardiovascular
diseases, nephropathy, infection and lower-extremity
amputations.
Hyperglycemia Adversely Affects Outcomes

9. Hyperglycemia Adversely Affects Outcomes
Hyperglycemia impacts
– Mortality
– Morbidity
– Rate of infections
– Length of hospital stay

10. Types Of Hyperglycemia in Hospitalized Patients

11. Hyperglycemia in Hospitalized Patients
• Pre-existing known diabetes
• Newly diagnosed diabetes
• Hospital related or stress hyperglycemia

13. Hospital related or stress hyperglycemia

15.  Stress hormones
cortisol, epinephrine  Glucose Production
 Lipolysis
FFAs
FFAs
+
 Glucose Uptake
Illness
Illness leads to Stress Hyperglycemia
 Glucose
 Fatty Acids

16.  Glucose Production
 Lipolysis
FFAs
FFAs
+
 Glucose Uptake
Hemodynamic insult
Electrolyte losses
Oxidative stress
Myocardial injury
Hypercoagulability
Altered immunity
 Wound healing
 Inflammation
 Endothelial function
 Stress hormones
cortisol, epinephrine
IllnessIllness
“Stress Hyperglycemia” Exacerbates Illness
 Glucose
 Fatty Acids

17. Traditionally acute hyperglycemia was defined
as RBS more than 200 mg/dl*
* (mcCowen et-el 2001 crit care clin 2001:17:107-24)

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

19. Strategy of In-Hospital Management of Diabetes

20.  Dose improving glycemic control improve
clinical outcomes for inpatients with
hyperglycemia ?
 What glycemic target can be recommended in
different patients ?
Strategy of In-Hospital Management of Diabetes

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
0
5
10
15
20
25
30
35
Total Non-ICU ICU
Normoglycemia Known diabetes New hyperglycemia
*
*P<.01 compared with normoglycemia and known diabetes.
*
*
Umpierrez GE et al. J Clin Endocrinol Metab. 2002;87:978-982.
Mortality(%)

24. Umpierrez et al. J Clin Endocrinol Metab 87:978, 2002
30
20
10
0
Mortality(%)
Normoglycemia Known New
Diabetes Hyperglycemia
10%
11%
31%*
*P<0.01
ICU Mortality
Hyperglycemia: An Independent Marker of
ICU Mortality

25. • No doubt that hyperglycemia is associated
with poor clinical outcomes
• However, it does not mean that treatment of
hyperglycemia will improve clinical outcomes

26. Intervention Studies

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
All Subjects (N = 620)
Standard treatment
0
.3
.2
.4
.7
.1
.5
.6
0 1
Years of Follow-up
2 3 4 5
Subjects at low CV risk and
w/ no prior insulin therapy
(N = 272)
Intensive management
0
.3
.2
.4
.7
.1
.5
.6
0 1
Years of Follow-up
2 3 4 5
RRR=28%
P=.011
RRR=51%
P=.0004
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. Intensive versus Conventional Glucose Control in Critically Ill
Patients
Randomized, prospective un-blinded clinical controlled trial
of 6104 patients.
NICE-SUGAR

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).

36. .
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.
NICE-SUGAR

37. 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
.
NICE-SUGAR

38. Results
Severe hypoglycemia(<40mg/dL) was recorded in 6.8%
of patients in the intensive control group, vs. 0.5%
in the conventional group.
NICE-SUGAR

39. These conflecting findinges have called to question the
benefit of tight control and highlight in the risk for severe
hyperglycemia
so

40. What glycemic target can be recommended in
different patients ?

41. ADA/AACE Inpatient Task Force
Endocrine Practice 2009;15;1-17
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
Recommended
140-180
Acceptable
110-140
Not recommended
< 110
Not recommended
>180

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. • Lower target acceptable
• ( 110-140 mg/dl )
AACE-ADA Consensus Statement on
Inpatient Glycemic Control: ICU
Moghissi E et al., Diabetes Care 2009;32:1344; Moghissi E et
al., Endocrine Practice 2009;15:353

44. • Tighter targets ( <110 mg/dl ) not safe;
• >180 mg/dl not acceptable.
AACE-ADA Consensus Statement on
Inpatient Glycemic Control: ICU
Moghissi E et al., Diabetes Care 2009;32:1344; Moghissi E et
al., Endocrine Practice 2009;15:353

45. ADA/AACE Inpatient Task Force
Endocrine Practice 2009;15:1-17
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

46. Achieving Tight Glycemic Targets
.What treatment options are available for achieving
optimal glycemic targets safely and effectively in specific
clinical situation?

47. Insulin
Oral Antidiabetes Agents
OR
Achieving Tight Glycemic Targets

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:

49. Disadvantages of most oral agents:
Slow-acting / difficult to titrate

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
The agent we
have
to control blood glucose
only
most powerfulpowerful

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.

54. Thank You
54

57. IV Insulin Therapy: Recommended Uses
 Continuous Variable Rate IV Insulin Drip
Major Surgery, NPO, Unstable, MI, DKA,
Hyperglycemia, Steroids, Gastroparesis,
Delivery, etc
 Basal / Bolus Therapy when eating
Best method to achieve quick glycemic control
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?

61. 1U to 1cc or 0.5U to 1cc of drip mixture

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. < 100 off
100-109 0.5
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.
Check BG every 1 hr and adjust
rate
The default insulin drip column

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

68. Correction Bolus Formula
Example:
–Current BG: 250 mg/dl
–Ideal BG: 100 mg/dl
–Glucose Correction Factor: 40 mg/dl
Current BG - Ideal BG
Glucose Correction factor
250 - 100
40
= ~4.0u

69. Calculating Initial MDI* Doses for Insulin-naïve
Patients
*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.
Starting dose = 0.5 × weight in kg
Basal dose = 40%-50%
of starting dose at bedtime
Total prandial dose = 50%-
60% of starting dose, 1/3 at
each meal*
Do not skip correction dose even if
no food eaten

Adjust upwards daily by adding 50%
of correction doses to basal and bolus
doses

70. Calculating Initial MDI* Dose: Example
*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.
Starting dose = 0.5 × 100 kg =50U
Basal dose =
0.4–0.5 x 50 U = 20-25 U at
bedtime
Prandial doses =
(0.5–0.6 x 50) = 25-30 U ÷ 3 or 8–
10 U at each meal*
Give correction dose

Assume 100-kg person with moderate insulin resistance

71. Non-ICU Hospital Management

72. Which is the outpatient regimen?
What is the current glucose
When is the patient to eat?
How well is it controlling glucose
Why is the patient admitted
What to do depends on several questions
Who is the patient?

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
0
5
10
15
20
25
30
35
< 109
mg/dL
109-125
mg/dL
126-162
mg/dL
>163
mg/dLBaker EH et al. Thorax. 2006;61:284-289.
N=433 patients with
COPD Exacerbations
Mortality(%)

74. New AACE-ADA Consensus Statement on Inpatient
Glycemic Control
- 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
Moghissi E et al. Diabetes Care 2009, Endocrine Practice 2009
Non–ICU
Setting

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

86. Does inpatient management of hyper-glycemia
represent a safety concerns?

87. Hypoglycemia

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
Beta-blockers ,Corticosteroids
medications

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.  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
Protocol for Insulin in Hospitalized Patient

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

94. All hospital patients should
have control blood glucose

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. When is the
patient to
eat?
What to do depends on several questions
How well is
it
controlling
glucose? What is the
current
glucose?
Why is the
patient
admitted?
Who
is the
patient?
Which is
the
outpatient
regimen?
• Type 1?
• Type 2?
• Orals?
• Insulin?
• Combo?
• A1c 6.5%?
• A1c 9.5%?
• BG=142?
• BG=442?
• NPO?
• Full diet?
• Sepsis?
• A-Fib?

100. Intervention Studies
Showing Benefits
• Van den Bergh-SICU
• Van den Bergh-MICU
• DIGAMI-1
• Krinsley study
• Furnary data
Showing No Benefits
• DIGAMI-2
• CREATE-ECLA
• VISEP trial
• GIST-UK
• Intra-operative cardiac
surgery study