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Inpatient Management of Diabetes

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Show Notes

Slide 1 :

Guillermo E. Umpierrez, MD, FACP, FACE Professor of Medicine Associate Director, Clinical Research Center Emory University School of Medicine Director, Diabetes & Endocrinology Grady Health System Management of Inpatient Hyperglycemia: Facts or Fiction

Slide 2 :

Umpierrez G et al. J Clin Endocrinol Metabol. 2002, 87:978-982. Levetan CS et al. Diabetes Care. 1998;21:246-249. Krinsley JS. Mayo Clin Proc. 2003;78:1471-1478. Falciglia M et al. 66th ADA Scientific Meeting, 2006. Hyperglycemia Is Common in Hospitalized Patients Non-critically ill medical/surgical: 38% Intensive care units (ICU): 29% – 100% Episodes of glucose >110 mg/dL: 100% Episodes of glucose >200 mg/dL: 31% Mean glucose >145 mg/dL: 39%

Slide 3 :

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. 2002;87:978-982. n=2020 *Hyperglycemia: Fasting BG >126 mg/dL or Random BG >200 mg/dL x 2

Slide 4 :

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

Slide 5 :

Blood Glucose (mg/dL) * * * * *P<0.05 vs BG<198 mg/dL (11 mmol/L) CAP, community acquired pneumonia Admission glucose (mg/dL) Patients McAlister et al. Diabetes Care. 2005;28:810-815. N=2471 patients with CAP Hyperglycemia and Pneumonia Outcomes

Slide 6 :

~2x Mortality Rate (%) Mean Glucose Value (mg/dL) Krinsley JS. Mayo Clin Proc. 2003;78:1471-1478. N=1826 ICU patients. 0 5 10 15 20 25 30 35 40 45 80-99 100-119 120-139 140-159 160-179 180-199 200-249 250-299 >300 0 5 10 15 20 25 30 35 40 45 0 5 10 15 20 25 30 35 40 45 Hyperglycemia and Mortalityin the MICU ~4x ~3x

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Slide 8 :

Does Controlling Hyperglycemia in the Hospital Matter? Summary: Observational Cohort Studies Inpatient hyperglycemia is common Inpatient hyperglycemia is associated with poor clinical outcome

Slide 9 :

Prospective study of 2467 consecutive patients with diabetes who underwent open heart surgery between 1/87 and 11/97 2467 patients 1499Continuous IV insulin (CII) BG goal: 150-200 mg/dL Furnary AP et al. Ann Thorac Surg. 1999;67:352-362. The Portland Diabetes Project 968Sliding-scale insulin (SSI)intermittent subcutaneous (SSI Q 4-hr)BG goal: ~200 mg/dL

Slide 10 :

DSWI, deep sternal wound infection; SCI, subcutaneous insulin; CII, continuous insulin infusion. 4.0 3.0 2.0 1.0 0.0 DSWI(%) 87 88 89 90 91 92 93 94 95 96 97 Year Patients with diabetes Patients without diabetes Furnary AP, et al. Ann Thorac Surg. 1999;67:352–362. CII (N=3554) SCI Portland Diabetes Project: Insulin Infusion Reduces DSWI

Slide 11 :

Blood Glucose (mg/dL) <150 150- 175 200- 225 175- 200 >250 225- 250 P<0.0001 *P<0.001 Postop Mortality BG <200 n=662 1.8% BG >200 n=1369 5.0% * Postop Mortality (%) Adjusted for 19 clinical and operation variables Furnary AP et al. Circulation. 1999:100 (Suppl I): I-591. 1.4 1.7 2.1 3.8 5.8 8.6 0 2 4 6 8 10 Hyperglycemia: A Predictor of Mortality Following CABG in Diabetics CABG, coronary artery bypass graft.

Slide 12 :

Intensive Insulin Therapy in Critically Ill Patients: The Leuven SICU Study Randomized controlled trial: 1548 patients admitted to a surgical ICU, receiving mechanical ventilation. Patients were assigned to receive either: Conventional therapy: IV insulin only if BG >215 mg/dL Target BG levels: 180-200 mg/dL Mean daily BG: 153 mg/dL Intensive therapy: IV insulin if BG >110 mg/dL Target BG levels : 80-110 mg/dL Mean daily BG: 103 mg/dL Van den Berghe et al. N Engl J Med. 2001;345:1359-1367.

Slide 13 :

Intensive Insulin Therapy in Critically Ill Patients: SICU * * * * * * *P<0.01 Van den Berghe et al. N Engl J Med. 2001;345:1359-1367. Relative Risk Reduction (%)

Slide 14 :

% Conventional treatment Intensive treatment Intention to Treat 26.8 24.2 40 37.3 ICU mortality Hospital mortality Hazard ratio 0.94 (95% CI 0.84–1.06) P=0.31 P=0.33 % ICU LOS =3 Days 38.1 31.3 52.5 43.0 ICU mortality Hospital mortality P=0.05 P=0.009 Intensive Insulin Therapy in MICU: Hospital Mortality Van den Berghe et al. N Engl J Med. 2006;354:449-461. A. B.

Slide 15 :

RCT, randomized clinical trial. Kitabchi & Umpierrez. Metabolism. 2008;57:116-120. RCT: Benefits of Tight Glycemic Control

Slide 16 :

Cost Savings with HospitalHyperglycemia Management Furnary1 – $5,580 per CABG patient per stay (LOS and DSWI) Van den Berghe2 – € 2,638 per patient per ICU stay (average ICU stay: 8.6 days conventional treatment vs. 6.6 days intensive treatment) Krinsley3 – $1.3M annual cost savings for a 305-bed community based hospital (14-bed ICU) Newton4 - $1.9 M annual cost saving for a 750 bed tertiary care center in North Carolina (non-ICU). Nurse case manager-based program (Endoc Practice 2006) Furnary AP, et al. Ann Thorac Surg. 1999;67:352–362; Van den Berghe et al. N Engl J Med. 2001; 345:1359-1367; Krinsley JS et al. Chest. 2006;129:644-650; Newton CA et al. Endocr Prac. 2006:12(suppl 3):43-48.

Slide 17 :

AACE - Consensus Conference Suggested Blood Glucose Targets Upper Limit Inpatient Glycemic Targets: ICU: 110 mg/dl (6.1 mmol/L) Non-critical care (limited data) Pre-prandial: 110 mg/dl (6.1 mM) Maximum: 180 mg/dL (10 mM) AACE- Endocrine Practice 10 (1): 77-82, 2004 AAE – Endocrine Practice February 2006 ADA- Diabetes Care 27: 553-591, 2004 The current ADA guideline for pre-prandial plasma glucose levels is 90–130 mg/dl

Slide 18 :

Glucose Levels in Hospitalized Patients with Diabetes Percent Good control Suboptimal control Poor control (80% in target) (40-80% in target) (<40% in target) Medical Floor Surgical Floor Target BG: preprandial BG 72-162 mg/dl Bhattacharyya et al, Diabet Med 19:412, 2002

Slide 19 :

Slide 20 :

Barriers to Improve Glycemic Control in Non-Critical Illness No prospective randomized interventional studies in general medicine/surgical services Concern about hypoglycemia is the leading limiting factor to improve glycemic control Fear of hypoglycemia leads to: Holding patient’s diabetic regimen Initiating “sliding scale” insulin coverage Delayed starting basal/bolus insulin therapy Clement et al, Diabetes Care 2004; 27(2): 553-97, Unger RH, N Engl J Med 1982; 306(21): 1294 Ben-Ami et al, Arch Intern Med 1999; 159(3): 281-4, Queale et al, Arch Intern Med 1997; 157(5): 545-52

Slide 21 :

Inpatient Management of Diabetes at a Large Teaching Hospital % 1 2 3 4 5 Hospital Day Schnipper et al, J Hosp Med, June 2006 Basal Insulin: 43% Meal-time insulin: 4% Sliding scale insulin: 90% The use of SSI alone was associated with a = 20 mg/dl daily BG compared to scheduled insulin and those not prescribed insulin at all.

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Slide 23 :

Current Controversies Around Tight Glucose Control in Critically Ill Patients Evidence for tight glycemic control What is the optimal BG target? Different insulin algorithms Is one insulin algorithm better than others? Kitabchi & Umpierrez. Metabolism. 2008;57:116-120.

Slide 24 :

To compare the effects of 2 regimens of insulin therapy on clinical outcome: 4.4 and 6.1 mmol/L (80 and 110 mg/dL)mean BG: 118 (109-131 mg/dL) 7.8 and 10.0 mmol/L (140 and 180 mg/dL)mean: 147 (127-163 mg/dL) Nondiabetic patients: 872 Diabetic patients: 210 Glucose Control in the ICU: How Low Should We Go? Preiser JC, SCCM Congress, Orlando, Feb 19, 2007 (submitted for publication). Glucontrol

Slide 25 :

Glucontrol Preiser JC, SCCM Congress, Orlando, Feb 19, 2007 (submitted for publication).

Slide 26 :

0.1621 53.8% 32.6% Death among patients with hypoglycemia <40, % Median (IQR) Preiser JC, SCCM Congress, Orlando, Feb 19, 2007 (submitted for publication). <0.0001 2.4% 8.6% Patients with hypoglycemia <40, % P Group B (n=546) Group A (n=536) Glucontrol

Slide 27 :

VISEP Trial Study Aim: to evaluate clinical outcome in 600 subjects with sepsis randomized to conventional or intensive insulin therapy in 18 academic hospitals in Germany. Primary Outcomes: Mortality (28 days) and morbidity (sequential organ failure dysfunction, SOFA Safety end-point: hypoglycemia (BG<40 mg/dl) Conventional Therapy: CII started at BG > 200 mg/dl and adjusted to maintain a BG 180 - 200 mg/dl. Intensive Therapy group: CII started at BG > 110 mg/dl and adjusted to maintain BG 80 -110 mg/dl (Leuven’s protocol) Brunkhorst et al, N Engl J Med 358:125-39, 2008

Slide 28 :

Blood Glucose Overall Survival VISEP Trial Days Conventional therapy Intensive therapy 0 1 2 3 4 5 6 7 8 9 Mean Blood Glucose (mg/dL) 10 11 12 13 14 0 50 100 150 200 0 10 20 30 40 50 60 70 80 90 100 Days Probability of Survival (%) Conventional therapy (n=290) Intensive therapy (n=247) 0 10 20 30 40 50 60 70 80 90 100 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.

Slide 29 :

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

Slide 30 :

Deedwania et al, Circulation, 117: 2008 Current Controversies Around Tight Glucose Control in Critically Ill Patients What is the optimal blood glucose target? ICU BG target: 80-110 mg/dl “Until further data are available, approximation of normoglycemia appears to be a reasonable goal (suggested plasma glucose 90 to 140 mg/dL), as long as hypoglycemia is avoided” (level of Evidence C)

Slide 31 :

Slide 32 :

Start CII at 2 U/h if BG 110-220 mg/dL or 4 U/h if BG >220 mg/dL.If BG <110 mg/dL, don’t start insulin, check BG every 4 h BG (mg/dL) Instructions >140 ? rate by 1–2 U/h 110-140 ? rate by 0.5–1 U/h Approaching range ? rate by 0.1–0.5 U/h 80-110 No change in rate 60 – 80 Reduce dose “adequately,” v BG within 1 h 40 - 60 Stop infusion (IV dextrose if BG <40), v BG within 1 h <40 Stop infusion, IV glucose 10 g IV boluses, v BG within 1 h Van den Berghe et al. N Engl J Med. 2001;395:1359-1367. Leuven Protocol CII, continuous infusion of insulin; BG, blood glucose; IV, intravenous.

Slide 33 :

300 - 329 24 330 - 359 4 330 - 359 8 330 - 359 14 >330 28 >360 6 >360 12 >360 16 Colum-Based Insulin Algorithm Davidson J et al. Diabetes Care. 2005;28:2418-2423.

Slide 34 :

GlucommanderPractical Alternative to IV Insulin Protocols Computer-based Insulin Infusion Protocols Davidson et al. Diabetes Care. 2005;28:2418-2423

Slide 35 :

Comparison of Insulin Infusion Protocols in the ICU: Glucommander vs. Standard Column-based Insulin Regimens CA Newton, D Smiley, PC Davidson, BW Bode, RD Steed, S Jacobs, AE Kitabchi, F Stentz, P Mulligan, GE Umpierrez Accepted for presentation, American Diabetes Association68th Scientific Sessions, June 6-10, 2008

Slide 36 :

Glucommander vs StandardMean Glucose Values Mean Glucose Maintained once Target Achieved Glucommander = 103.4 ± 9 mg/dL Standard = 120.4 ± 18 mg/dL * p < 0.0001 Newton CA et al. ADA Scientific Meeting. June 2008.

Slide 37 :

Hypoglycemia and Hyperglycemia After Target Achieved (Patients) P=NS P=NS P=0.02 Newton CA et al. ADA Scientific Meeting. June 2008.

Slide 38 :

Results Clinical Outcomes Newton CA et al. ADA Scientific Meeting. June 2008.

Slide 39 :

Methods for Managing Hospitalized Persons With Diabetes Non-ICU Basal/bolus therapy (MDI) NPH and Regular insulin Long-acting and rapid-acting insulin Premix insulin Sliding Scale Short-Acting Insulin

Slide 40 :

Problems with Conventional Approach Conventional Insulin Rx. Limitations B L S HS B Reg NPH Insulin Effect Meals NPH Reg Lacks flexibility Poor match between regular insulin and meals - initial hyperglycemia - late hypoglycemia Fasting hyperglycemia

Slide 41 :

Sliding-Scale Regular Insulin Adapted from the following sources: DeWitt DE and Dugdale DC. JAMA. 2003;289:2265-2269. Skyler JS. In: DeFronzo RA, ed. Current Therapy of Diabetes Mellitus. St Louis, MO: Mosby–Year Book, Inc. 1998:36-49.

Slide 42 :

Multi Dose Insulin Injections 21:00 18:00 Breakfast Lunch Dinner 12:00 8:00 Time Glargine Insulin Action Glargine QD + rapid-acting analog AC

Slide 43 :

Umpierrez et al, Diabetes Care 30:2181–2186, 2007

Slide 44 :

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

Slide 45 :

SSRI Regimen Umpierrez et al, Diabetes Care 30:2181–2186, 2007

Slide 46 :

Mean Blood Glucose Levels During Insulin Therapy * p<0.01 ¶ p<0.05 ¶ * * * ¶ ¶ ¶ Day 3: P=0.06 Umpierrez et al, Diabetes Care 30:2181–2186, 2007

Slide 47 :

Basal–Bolus Insulin Regimen in Noncritically Ill Patients

Slide 48 :

Basal-Bolus Insulin Therapy vs Sliding Scale Insulin in Hospitalized Patients with T2DM The mean insulin daily dose was significantly higher in the basal-bolus group than in the SSI group Umpierrez GE et al. Diabetes Care 2007;30:2181-2186.

Slide 49 :

Hypoglycemia Basal Bolus Group: 1,005 BG readings Two patients (3%) had BG < 60 mg/dL Four BG readings (0.4%) < 60 mg/dL No BG < 40 mg/dL SSRI: 1,021 BG readings Two patients (3%) had BG < 60 mg/dL Two BG readings (0.2%) < 60 mg/dL No BG < 40 mg/dL None of the episodes of hypoglycemia in either group were associated with adverse outcomes Umpierrez GE et al. Diabetes Care 2007;30:2181-2186.

Slide 50 :

DEtemir plus Aspart vs.NPH plus Regular in Medical Patients with T2DM (DEAN Trial) 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 American Diabetes Association68th Scientific Sessions, June 6-10, 2008

Slide 51 :

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 (Levemir®) and half as aspart (Novolog®) Insulin detemir - once daily, at the same time of the day. Insulin aspart - three equally divided doses (AC) Smiley et al. ADA Scientific Meeting. June 2008.

Slide 52 :

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 (Novolin N®) and two-fifth as regular (Novolin R®) NPH insulin– twice daily, 2/3 before breakfast, 1/3 before dinner Regular insulin- twice daily, 2/3 before breakfast, 1/3 before dinner Smiley et al. ADA Scientific Meeting. June 2008.

Slide 53 :

Blood glucose (mg/dL) Duration of Therapy (days) Detemir + Novolog NPH + Regular DEAN-Trial Basal/bolus regimen: Detemir was given once daily and Novolog before meals. NPH/regular regimen: NPH and Regular insulin were given twice daily, 2/3 A.M., 1/3 P.M. Data are ± SEM

Slide 54 :

Hypoglycemia Detemir/Aspart Group: 1,090 BG readings 18 patients (27.7%) had BG < 60 mg/dL 19 BG readings (1.7%) < 60 mg/dL 2 BG < 40 mg/dL (0.2%) NPH/Regular Group: 1,038 BG readings 12 patients (18.5%) had BG < 60 mg/dL 13 BG readings (1.3%) < 60 mg/dL 2 BG < 40 mg/dL (0.2%) None of the episodes of hypoglycemia in either group were associated with adverse outcomes Smiley et al. ADA Scientific Meeting. June 2008.

Slide 55 :

Number of Publications in PubMed Search for Glucose and Critical Care 21 47 301 Number PubMed Articles www.pubmed.gov, accessed 4-5-2008 33 151

Slide 56 :

Inpatients Diabetes ManagementSummary: Hyperglycemia is frequent in hospitalized patients with and without history of diabetes Hyperglycemia (hypoglycemia?) is a marker of poor outcome in critically and non-critically ill patients Improvement in clinical outcome has been shown by improved glycemic control in a variety of inpatient settings

	geumpie@emory.edu 1 Years ago. Category: Internal Medicine

Tags:	Internal Medicine

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