Deepika Reddy MD Department of Endocrinology 

 Management of hyperglycemic crisis  Review need for inpatient glycemic control  Brief overview of relevant trials  Case based review of diabetes management strategies/review guidelines   

Pathophysiology of DKA and HHS

Kitabchi A E et al. Dia Care 2006;29:2739-2748

Copyright © 2011 American Diabetes Association, Inc.

Protocol for the management of adult patients with DKA. *DKA diagnostic criteria: serum glucose >250 mg/dl, arterial pH <7.3, serum bicarbonate <18 mEq/l, and

moderate ketonuria or ketonemia.

Kitabchi A E et al. Dia Care 2006;29:2739-2748

Copyright © 2011 American Diabetes Association, Inc.

Protocol for the management of adult patients with HHS. HHS diagnostic criteria: serum glucose >600 mg/dl, arterial pH >7.3, serum bicarbonate >15 mEq/l, and minimal

ketonuria and ketonemia.

Kitabchi A E et al. Dia Care 2006;29:2739-2748

Copyright © 2011 American Diabetes Association, Inc.

  Patients with known diabetes     Patients with undiagnosed diabetes     Stress hyperglycemia 

  Has an effect on  Morbidity (including infection rates)  Mortality    Length of stay 

Previous History DM New hyperglycemia

Normoglycemic

2030 consecutive adult patients admitted between July and October 1998

38% had hyperglycemia*

Umpierrez et al. J Clin Endocrinol Metab. 2002;87:978-982. slide from desantis ACPONLINE

*Hyperglycemia defined as admission or FPG ≥126 mg/dL or random BG ≥200 mg/dL

0

5

10

15

20

25

30

35

Normoglycemia Known Diabetes Newhyperglycemia

0

5

10

15

20

25

30

35

Normoglycemia Known Diabetes Newhyperglycemia

1.7%

16%*

3%

10% 11%

31%†

Total Inpatient Mortality

ICU Mortality

*P<0.01

n=1886

†P<0.01

n=243

Umpierrez et al. J Clin Endocrinol Metab. 2002;87:978-982 slide from desantis ACPONLINE .

0

0.5

1

1.5

2

2.5

3

3.5

4

<150 150-175 175-200 200-225 225-250 >250

Rat

e of

infe

ctio

n, %

3-day average postoperative blood glucose, mg/dL

P=0.001

Note inflection

point

Rates of deep sternal wound infection in 4864 patients with diabetes who underwent an open-heart surgical procedure

Furnary et al. Endocr Pract. 2004;10(suppl 2):21-33.

Reprinted from Furnary AP, et al. J Thorac Cardiovasc Surg. 2003;125:1007–1021 with permission from American Association for Thoracic Surgery. Purple: No DM

CII

10

8

6

4

0

Mortality (%)

87 88 89 90 91 92 93 94 98 99 00

Year

Patients with diabetes

Patients without DM diabetes

2

95 96 97 01

HYPERGLYCEMIA Index of disease severity

0

5

10

15

<150 150-175

176-200

201-225

226-250

>250

CardiacNon-Cardiac

0.9% 1.3% 2.3%

4.1% 6.0%

14.5%

Average post-op glucose

Mo

rta

lity

%

Furnary et al J Thorac Cardiovasc Surg 2003;125:1007-21

13

  Intensive therapy to achieve blood glucose levels of 80–110 mg/dL reduced mortality (‐34%), sepsis (‐46%), dialysis (‐41%), blood transfusion (‐50%), and polyneuropathy (‐44%) 

van den Berghe G, et al. N Engl J Med. 2001;345:1359–1367.

-60

-50

-40

-30

-20

-10

0

Reduction (%)

Mortality Sepsis Dialysis Polyneuropathy Blood

Transfusion

34%

46% 41%

44% 50%

N = 1,548

NEJM 2001;345:1359-67

Blood Glucose Overall Survival

VISEP Trial

Days

Conventional therapy Intensive therapy

0 1 2 3 4 5 6 7 8 9

Mea

n B

lood

Glu

cose

(m

g/dL

)

10 11 12 13 14 0

50

100

150

200

0 10

20

30

40

50

60

70

80

90 100

Days

Prob

abili

ty o

f Su

rviv

al (

%)

Conventional therapy (n=290)

Intensive therapy (n=247)

0

20

40

60

80

100

Brunkhorst FM et al. N Engl J Med. 2008;358:125-139.

Data from 537 patients: 247 received IIT goal: 80 – 110 mg/dL: mean BG 112 mg/dL 290 received CIT goal: 180 – 200 mg/dL: mean BG 151 mg/dL IIT, intensive insulin therapy; CIT, conventional insulin therapy.

VISEP Trial

Brunkhorst FM et al. N Engl J Med. 2008;358:125-139.

IIT (n=247)

CIT (n=290) P

Mortality rate, % 28 days 90 days

24.7 39.7

26.0 35.4

0.74 0.31

% of Patients with glucose ≤40 mg/dL 17.0% 4.1% <0.001

SOFA* score (mean) 95% CI

7.8 7.3-8.3

7.7 7.3-8.2

0.16

*SOFA – sequental organ failure assessment

NEJM2009;360:1283-97

NICE SUGAR

Griesdale et al., CMAJ 2009;180:821

Favors IIT Favors Control Hypoglycemic events

  A 60 year old gentleman with a history of smoking is 

admitted to the hospital with pneumonia. He is started on antibiotics and nebuliser treatments. He has a blood sugar on initial evaluation of 150  

  Would you start point of care blood sugar monitoring in this patient? 

     If blood sugars remain elevated would you get a HbA1c?  

Test Normal Prediabetes Diabetes

Hemoglobin A1C

<5.7% 5.7-6.4% >6.5 %

The patient continues to have blood sugars in the 180 to 200 range. What would you do? 

   What are blood sugar goals in the hospital setting?     What treatment would  you use for blood sugar control in the hospital? 

   If using insulin what regimen would you use?    

  The endocrine society guidelines recommend:   Pre‐meal blood gluose <140 mg/ dL.Random blood glucose <180 mg/ dL 

  In other words 140‐180 desired, in some situations 110‐140 acceptable. Blood sugars outside of these ranges ( <110 or >180 ) not acceptable 

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

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

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

 What would you use to treat the patient?   Stop Orals   Use Basal Insulin  

Medication  Primary complication 

Sulfonylurea  Hypoglycemia 

Metformin  Lactic acidosis, careful peri‐op, if getting dye 

TZD  CHF, CAD, Bladder CA 

Alpha glucosidase inhibitors  Diarrhea 

Incretin  Only helpful when eating, GI side‐effects 

  Stop orals    Treat with Insulin   Use basal (either with supplemental scale or bolus) 

  0.4 or 0.5 unit/kg/day in normal patients.50% of this would be basal needs. 

  0.3 units/kg/ day in elderly and renal failure   0.2 or 0.25 units/kg a day if NPO 

  Hyperglycemia is unfavorable, but hypoglycemia is also associated with adverse outcomes 

     To avoid hypoglycemia, the insulin regimen should be reassessed if blood glucose levels fall below 100 mg/ DL 

 

  Patient on tube feeds or parenteral nutrition    Started on meds that cause hyperglycemia 

  Patient on tube feeds or parenteral nutrition    Started on meds that cause hyperglycemia 

  What regimen should the patient use at home?       What other aspects of care should be addressed? 

Multidisciplinary Team Extends Beyond Caregivers 

GLYCEMIC CONTROL

COMMITTEE

Endocrin-ologists

Hospitalists

P&T Committee

Nursing groups

Other internists

Pharmacists

Critical Care physicians

Patient Safety

Committee

Forms Committee Nutritionists/

Dietitians

Patient Representa-

tives

Hospital Informatics

Performance Improvement/

QI staff

Unit clerks/ secretaries

Chief residents/ residency program

directors Biomedical,

medical records, CPOE expertise

Departmental committees

Surgery, Trauma,

Orthopedics, Anesthesiology

leaders

Lab

Maynard et al. SHM Glycemic Control Workgroup. Available at: :http://www.hospitalmedicine.org/AM/Template.cfm? Section=Quality_Improvement_Resource_Rooms1&Template=/CM/HTMLDisplay.cfm&ContentID=4337.

OR or

Perioperative Committees