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umpierrezInpatientnonicuGuidelines1.ppt
1. Clinical Guidelines for the
Management of Hyperglycemia in
Hospitalized Patients in a Non-
Critical Care Setting
Work in Progress
The Endocrine Society,
European Endo Society,
American Heart Association,
American Diabetes Association,
Society of Hospitalist Medicine,
American Association of Diabetes Educators
2. Inpatient Hyperglycemia in non-critical
care setting
1. What is the frequency of hyperglycemia and
diabetes?
2. What diagnosis criteria should we use?
3. What is the association between hyperglycemia
and outcomes?
4. How should we manage hyperglycemia in non-
ICU setting?
3. Hyperglycemia: Scope of the Problem
Kosiborod M, et al. J Am Coll Cardiol. 2007;49(9):1018-183:283A-284A.
No Diabetes
26%
Diabetes 50
40
30
20
10
0
<110 110-140
50
40
30
20
10
0
<110 110-140 140-170170-200 >200
78%
140-170170-200 >200
Mean BG, mg/dL
Patients,
%
4. Hyperglycemia*: A Common Comorbidity
in Medical-Surgical Patients in a
Community Hospital
62%
12%
26%
Normoglycemia
Known Diabetes
New Hyperglycemia
Umpierrez G et al, J Clin Endocrinol Metabol 87:978, 2002
n = 2,020
* Hyperglycemia: Fasting BG 126 mg/dl
or Random BG 200 mg/dl X 2
5. New and Stress hyperglycemia
Patients with hyperglycemia without a
previous history of diabetes should be tested
with a hemoglobin A1C during the hospital
stay or with an oral glucose tolerance test
after discharge to confirm the diagnosis of
diabetes.
Less than 35% of patients had normal
glucose tolerance after 3 to 12 months of
follow-up.
Norhammar et al. Lancet 2002; 359(9324): 2140-4.
Arora et al. Endocr Pract 2009; 15(5): 425-30.
Greci et al. Diabetes Care 2003; 26(4): 1064-8.
6. IGT and Undiagnosed T2DM are
Common in Acute MI and Stroke
Norhammar A, et al. Lancet 2002;359:2140−4.
Matz K, et al. Diabetes Care 2006;792−7.
2-hour OGTT
70
60
50
40
30
20
10
0
Norhammar
(n=181)
Matz
(n=238)
Patients
(%)
66
39
Myocardial infarction
Stroke
IGT Undiagnosed T2DM
35
23
31
16
7. Epidemiology of Inpatient Hyperglycemia
in non-critical care setting
1. What is the frequency of hyperglycemia and
diabetes?
2. What diagnosis criteria should we use?
3. What is the association between hyperglycemia
and outcomes?
4. How should we manage hyperglycemia in non-
ICU setting?
8. NORMAL IFG or IGT
PREDIABETES
DIABETES
FPG < 100 mg/dl FPG > 100 - 125
mg/dl
(IFG)
FPG > 126 mg/dl
2-h PG < 140
mg/dl
2-h PG > 140 -
199 mg/dl
(IGT)
2-h PG > 200 mg
Random PG > 200
+ symptoms
A1C 5.7% to 6.4% ≥ 6.5%
ADA 2010 - Categories of Increased
Risk for Diabetes*
ADA Clinical Practice Recommendations, January 2019
9. A1C for Diagnosis of Diabetes in the
Hospital
Inhospital hyperglycemia is defined as an
admission or inhospital BG > greater 140 mg/dl.
HbA1c > 6.5% can be identified as having
diabetes, and patients with A1C 5.7%-6.4% can
be considered as being at risk for diabetes.
Implementation of A1C testing can be useful:
assess glycemic control prior to admission
assist with differentiation of newly diagnosed diabetes
from stress hyperglycemia
designing an optimal regimen at the time of discharge
10. Comparison of sensitivity and specificity
achieved for the diagnosis of diabetes based
on FPG, at various levels of HbA1c, from
NHANES III and 1999–2004 NHANES
J Clin Endocrinol Metab, July 2008, 93(7):2447–2453
12. Epidemiology of Inpatient Hyperglycemia
in non-critical care setting
1. What is the frequency of hyperglycemia and
diabetes?
2. What diagnosis criteria should we use?
3. What is the association between hyperglycemia
and outcomes?
4. How should we manage hyperglycemia in non-
ICU setting?
14. Community Acquired Pneumonia Outcomes
in Patients with Diabetes
0
20
40
60
80
100
%
Hospitalization Mortality Pleural Effusion Concomitant
Illnesses
P: < 0.001
N= 660 (DM: 106 & non-DM: 554)
No differences in microorganisms and bacteremia rates
Falguera et al, Chest 128:3233-3239, 2005
*
*
*
*
93
8
17
78
31
18
53
40
*
Diabetes
No Diabetes
15. A case control study of 108,593
patients who underwent
noncardiac surgery.
*Odds ratio for perioperative
mortality is 1.19 (95% CI 1.1–
1.3) per mmol/l increase of
glucose level
16. Thirty Day Mortality and Inhospital Complications
in diabetic and non-diabetic subjects
†p = 0.1
* p= 0.001
#p=0.017
†
*
*
*
*
#
*
%
A Frisch et al. Diabetes Care, May 2010
17. Hyperglycemia and mortality
Mean POSTSURGERY blood glucose and ODDS RATIOS for 30 day
mortality in diabetic and non diabetic patients
0
10
20
30
40
50
60
50 100 150 200 250 300
Odds
ratio
for
30-day
mortality
Meanbloodglucoseaftersurgery(mg/dl)
All patients Diabetics non-Diabetics
A Frisch et al. Diabetes 58 (suppl 1) A27, 2009
18. Hyperglycemia: An Independent Marker of
In-Hospital Mortality in Patients with
Undiagnosed Diabetes
Total In-patient Mortality
Normoglycemia Known New
Diabetes Hyperglycemia
1.7%
3.0%
16.0% *
Mortality
(%)
* P < 0.01
Umpierrez GE et al, J Clin Endocrinol Metabol 87:978, 2002
19. AACE/ADA Target Glucose Levels
in Non–ICU Patients
Glucose Target in non–ICU setting:
Premeal 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 and/or above these
cut-points
Moghissi ES, et al; AACE/ADA Inpatient Glycemic Control Consensus Panel. Endocr Pract. 2009;15(4).
http://www.aace.com/pub/pdf/guidelines/InpatientGlycemicControlConsensusStatement.pdf
20. Epidemiology of Inpatient Hyperglycemia
in non-critical care setting
1. What is the frequency of hyperglycemia and
diabetes?
2. What diagnosis criteria should we use?
3. What is the association between hyperglycemia
and outcomes?
4. How should we manage hyperglycemia in non-
ICU setting?
21. 1.ACE/ADA Task Force on Inpatient Diabetes. Diabetes Care. 2006 & 2009
2.Diabetes Care. 2009;31(suppl 1):S1-S110..
Antihyperglycemic Therapy
Insulin
Recommended
OADs
Not Generally
Recommended
IV Insulin
Critically ill patients
in the ICU
SC Insulin
Non-critically ill
patients
Recommendations for Managing Patients
With Diabetes in the Hospital Setting
22. AACE/ADA Consensus Statement
Non-insulin therapies in the hospital?
Sulfonylureas are a major cause of hypoglycemia
Metformin contraindicated in setting of decrease renal
blood flow and with use of iodinated contrast dye
Thiazolidinediones associated with edema and CHF
α glucosidase inhibitors are weak glucose lowering
agents
Pramlintide and GLP1-directed therapies can cause
nausea and have a greater effect on postprandial
glucose
Moghissi ES, et al; AACE/ADA Inpatient Glycemic Control Consensus Panel. Endocr Pract. 2009
23. Management of Hyperglycemia and
Diabetes in non-ICU Setting
Non-ICU
Sliding Scale Short-Acting Insulin
Basal/bolus therapy (MDI)
• NPH and Regular insulin
• Long-acting and rapid-acting insulin
Premix insulin
24. Study Type: Prospective, multicenter, randomized,
open-label trial
Patient Population: 130 subjects with DM2
Diet and/or oral hypoglycemic agents
Umpierrez et al, Diabetes Care 30:2181–2186, 2007
25. D/C oral antidiabetic drugs on admission
Starting total daily dose (TDD):
0.4 U/kg/d x BG between 140-200 mg/dL
0.5 U/kg/d x BG between 201-400 mg/dL
Half of TDD as insulin glargine and half as rapid-
acting insulin (lispro, aspart, glulisine)
Insulin glargine - once daily, at the same time/day.
Rapid-acting insulin- three equally divided doses (AC)
Randomized Basal Bolus versus Sliding Scale Regular
Insulin in patients with type 2 Diabetes Mellitus
(RABBIT-2 Trial)
Umpierrez et al, Diabetes Care 30:2181–2186, 2007
27. Rabbit 2 Trial: Changes in Glucose Levels With
Basal-Bolus vs. Sliding Scale Insulin
Umpierrez GE, et al. Diabetes Care. 2007;30(9):2181-2186.
Days of Therapy
BG,
mg/dL
100
120
140
160
180
200
220
240
Admit 1
Sliding-scale
Basal-bolus
bP<.05.
a
a a
b b
b
b
2 3 4 5 6 7 8 9 10
aP<.05.
• Sliding scale regular insulin (SSRI) was given 4 times daily
• Basal-bolus regimen: glargine was given once daily; glulisine was given before meals.
0.4 U/kg/d x BG between 140-200 mg/dL
0.5 U/kg/d x BG between 201-400 mg/dL
29. Study Type: Prospective, randomized, open-label trial
Patient Population: 130 subjects with DM2
Oral hypoglycemic agents or insulin therapy
Study Sites: Grady Memorial Hospital, Atlanta, GA
Rush University Medical Center, Chicago, IL
Umpierrez et al, J Clin Endocrinol Metab 94: 564–569, 2009
30. Detemir–Aspart Insulin Regimen
• D/C oral antidiabetic drugs on admission
• Starting total daily dose (TDD):
– 0.4 U/kg/d x BG between 140-200 mg/dL
– 0.5 U/kg/d x BG between 201-400 mg/dL
• Half of TDD as insulin detemir and half as aspart
– Insulin detemir - once daily, at the same time of the
day.
– Insulin aspart - three equally divided doses (AC)
Umpierrez et al, J Clin Endocrinol Metab 94: 564–569, 2009
31. NPH–Regular Split-Mixed Regimen
• D/C oral antidiabetic drugs on admission
• Starting total daily dose (TDD):
– 0.4 U/kg/d x BG between 140-200 mg/dL
– 0.5 U/kg/d x BG between 201-400 mg/dL
• Three-fifth of TDD as insulin NPH and two-fifth
as regular
– NPH insulin– twice daily, 2/3 before breakfast, 1/3
before dinner
– Regular insulin- twice daily, 2/3 before breakfast, 1/3
before dinner
Umpierrez et al, J Clin Endocrinol Metab 94: 564–569, 2009
32. DEAN Trial: Changes in Mean Daily
Blood Glucose Concentration
BG,
mg/dL
Duration of Therapy, d
Data are means SEM.
Detemir + aspart
NPH + regular
Basal-bolus regimen: detemir was given once daily; aspart was given before meals.
NPH/regular regimen: NPH and regular insulin were given twice daily, two thirds in AM, one third in PM.
Umpierrez GE, et al. J Clin Endocrinol Metab. 2009;94(2):564-569.
P=NS
100
120
140
160
180
200
220
240
Pre-Rx
BG
0 1 2 3 4 5 6-10
35. p-value*
variable BG < 60 mg/dl BG < 70 mg/dl
AGE 0.036 0.001
wt 0.027 0.001
A1C 0.521 0.658
Creatinine 0.011 0.002
Enrollment BG 0.166 0.319
Previous treatment 0.005 <.001
Previous insulin Rx <0.001 <.001
Treatment group <0.001 <.001
*p-values are from Wilcoxon Two-Sample Test
Summary of Univariate Analyses
Umpierrez et al, ADA Scientific Meeting, Poster #516, 2009
36. RAndomized Study of Basal Bolus Insulin
Therapy in the Inpatient Management of
Patients with Type 2 Diabetes Undergoing
General Surgery: RABBIT Surgery Trial
Guillermo E Umpierrez, Dawn Smiley, Sol Jacobs,
Limin Peng, Angel Temponi, Christopher Newton,
Denise Umpierrez, Patrick Mulligan, Darin Olson,
Jana MacLeod, Monica Rizzo.
Umpierrez et al, Preliminary data- ADA Scientific Session 2010
37. Research Design and Methods
Study Type: Multi-center, prospective, open-label
randomized clinical trial
Patient Population: Patients with type 2 DM admitted to
general surgery services
Study Sites: Grady Memorial Hospital, Veterans Affairs
Medical Center and Emory University Hospital, Atlanta, GA
Treatment Groups:
Group 1: basal/bolus regimen with glargine once daily
and glulisine before meals
Group 2: sliding scale regular insulin (SSRI) four times
daily
Umpierrez et al, Preliminary data- Abstract submitted to ADA Scientific Session 2010
38. Primary outcome:
• Differences between groups in mean daily BG
concentration
• Composite of hospital complications including:
postoperative wound infection, pneumonia, respiratory
failure, acute renal failure, and bacteremia.
Secondary outcome:
Differences between groups in any of the following measures:
• Mean fasting and pre-meal BG, number of hypoglycemic
(BG < 70 mg/dL and < 40 mg/dL) and hyperglycemic (BG
> 200 mg/dL) events , length of hospital stay, need for
ICU care, and rate of complications including wound
infection, pneumonia, acute renal failure, and mortality.
39. 211 Patients with type 2 DM that underwent general surgery
Glargine + Glulisine
(Gla+Glu)
N= 104
Group 1: 0.5 U/kg
Half as glargine once daily
Half as glulisine before meals
Sliding scale insulin
(SSRI)
N= 107
OPEN-LABELED RANDOMIZATION
Group 2:
4 times/day for BG >140 mg/dl
RABBIT SURGERY TRIAL
40. RABBIT 2 SURGERY
Umpierrez et al, Preliminary data- Abstract to be submitted_ADA Scientific Session 2010
45. Umpierrez et al, Preliminary data- Abstract to be submitted_ADA Scientific Session 2010
Hypoglycemic Events
46. Treatment with glargine once daily plus glulisine
before meals improved glycemic control and
reduced hospital complications compared to SSRI
in general surgery patients with T2DM.
Our study indicates that basal/bolus insulin
regimen is the preferred insulin regimen in the
hospital management of general surgery patients
with type 2 diabetes.
Summary & Conclusion
RABBIT 2 SURGERY
47. Management Recommendations
All patients with T1DM must receive insulin treatment
with basal bolus, multi-dose insulin combination of
NPH plus regular insulin or continuous insulin pump.
Patients treated with insulin at home should be
continued with insulin therapy in the hospital.
Scheduled subcutaneous basal bolus insulin regimen
is preferred for the majority of non-critically ill
patients with hyperglycemia.
The practice of using sliding scale insulin (SSI) as a
single form of therapy is undesirable.
48. Strategies for Preventing Hypoglycemia
In-service training on new treatment
modalities and the actions of new
antihyperglycemic agents
Braithwaite SS, et al. Endocr Pract. 2004;10(suppl 2):89-99.
Reducing outpatient insulin dose in patients
treated with insulin prior to admission
Basal Bolus is preferred over SSRI and
NPH/regular combination
49. D/C oral antidiabetic drugs on admission
Starting total daily dose (TDD):
0.3 U/kg/d in elderly and renal failure (lean?)
0.4 U/kg/d x BG between 140-200 mg/dL
0.5 U/kg/d x BG between 201-400 mg/dL
Half of TDD as insulin glargine and half as rapid-
acting insulin (lispro, aspart, glulisine)
Decrease outpatient insulin dose by 20-25%
Basal Bolus Insulin Regimen in T2DM: Summary
Umpierrez et al, Diabetes Care 2007; JCEM 2009; Diabetes 2010
51. 4:00 16:00 20:00 24:00 4:00 8:00
12:00
8:00
Time
Glargine once
daily
0.25 U/kg
Basal-PLUS Insulin Regimen
Insulin
Action
Leahy J. In: Leahy J, Cefalu W, eds. Insulin Therapy.
New York: Marcel Dekker; 2002:87; Nathan DM. N Engl J Med. 2002;347:1342
Aspart, Lispro or Apidra before
meals per sliding scale
52. A1C < 7%
Re-start
outpatient
treatment
regimen
(OAD and/or
insulin)
A1C 7%-9%
Re-start
outpatient oral
agents and D/C
on glargine once
daily at 50-80%
of hospital dose
A1C >9%
D/C on basal bolus at
same hospital dose.
Alternative: re-start
oral agents and D/C
on glargine once
daily at 50-80% of
hospital dose
Discharge insulin Algorithm
Discharge Treatment
53. Needed Research Studies
What is the role of medical nutrition therapy in non-
critical care setting?
How should glycemia be monitored in non-critical
care setting?
How should hyperglycemia be managed across
transitions in care?
What are the best predictors of hypoglycemia?
What is the financial impact of glycemic control in
non-critical care areas?
