1. Update - Inpatient Diabetes and Hyperglycemia Review of Recent Developments in Context Greg Maynard MD, MSc UCSD

2. Outline Background Infusion Insulin – Critical Care Transition from Infusion Clinical Inertia and SC insulin Hypoglycemia Transition Home – Glitazones New Tools / Resources

3. Inpatient Hyperglycemia and Poor Outcomes- Background Robust physiologic rationale Consistent dose-response relationship in dozens of observational / epidemiologic studies Observations of non-RCT interventions (like Portland protocol, Krinsley) show benefit. Influential RCTs showed benefit of tight glycemic control

4. Intensive Insulin Therapy in Critically Ill Surgical Patients Setting: Belgian SICU, University Hospital Hypothesis: normalization of blood glucose levels with insulin therapy can improve prognosis of patients with hyperglycemia or insulin resistance Design: prospective, RCT Conventional: insulin when blood glucose > 215 mg/dL Intensive: insulin when glucose > 110 mg/dL and maintained at 80–110 mg/dL van den Berghe G, et al. N Engl J Med. 2001;345:1359–1367.

5. Intensive Insulin Therapy in Critically Ill Patients * * * * * * * P < 0.01 Van-Den Berge et al, NEJM 345:1359, 2001 Relative Risk reduction (%)

6. AACE - Consensus Conference 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 ADA- Diabetes Care 27: 553-591, 2004 The current ADA guideline for pre-prandial plasma glucose levels is 90–130 mg/dl

7. Things Get More Complicated

8. Intensive Insulin Therapy in the Medical ICU Greet Van den Berghe, M.D., Ph.D., and the Leuven Group N Engl J Med, Volume 354;5:449-461, February 2, 2006 RCT of insulin infusion to goal of 80-110 mg/dL vs usual therapy (180-200 mg/dL). 1,200 patients randomized A priori outcome of interest: patients in MICU for > 3 days Only 17% were diabetic

9. Intensive Insulin Therapy in MICU: Hospital Mortality Van-Den Berge et al, NEJM 354:449-61, 2006 % 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 Mortality Reduction 17.9% Mortality Reduction 18.1%

10. Conclusions: MICU study Intensive insulin therapy significantly reduced overall morbidity but not mortality. Predefined population analysis (ICU > 3 d): –In-house mortality reduced (ARR 9.5%) –ICU mortality reduced (ARR 7.2%) p=.05 –Morbidity Reduced BUT, More deaths (18.8 vs 26.8%) in patients in ICU < 3 days (NS w/ adjustment) More studies needed.

11. Efforts to Validate The Goals Coming from the Van den Berghe Trials Glucontrol VISEP NICE-SUGAR

12. Glucontrol Study (abstract info) Mixed population of ICU patients N = ~3500, multicenter, Europe Target glucose: –80 – 110 mg/dl vs. 140 – 180 mg/dl Endpoint: in-hospital and 28 day mortality Start: October 2004

13. Group A (n = 550) Group B (n = 551) P Age, yr 65 (51-74) 65 (51 – 74) 0.9207 Sex ratio, M/F 352/198338/2130.3827 Category Medical Medical Scheduled Surgery Scheduled Surgery Emergency Surgery Emergency Surgery Trauma Trauma 42.9 % 31.3 % 18.1 % 7.7 % 41.2 % 32.7 % 18.1 % 7.9 % 0.9437 GLUCONTROL Philippe Devos, MD Jean-Charles Preiser MD, PhD University Hospital of Liège - Belgium

14. 300 250 200 150 100 50 Group A Blood glucose, mg/dl Group B p < 0.0001GLUCONTROL 119 mg/dl 147 mg/dl

15. Group A (n = 550) Group B (n = 551)P ICU death rate, %16.715.20.5022 Hospital death rate, %24.520.70.1452 Day 28 death rate, %19.516.20.1685 Median (IQR)GLUCONTROL Hypoglycemia 8.6% vs 4%

16. VISEP Trial Brunkhorst et al, N Engl J Med 358:125-39, 2008

17. 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

18. 0.167.87.3-8.37.77.3-8.3 SOFA Score 0.740.3126%35.4%24.7%39.7% Mortality rate, % - 28 days - 28 days - 90 days - 90 days PCIT (n = 290) IIT (n = 247) < 0.0001 4.1 % 17.0 % Patients with hypoglycemia < 40, % Brunkhorst et al, N Engl J Med 358:125-39, 2008 Data from 488 patients: IIT [goal: 80 – 110 mg/dL]: mean BG 112 mg/dl CIT [goal: 180 – 200 mg/dL]: mean BG 151 mg/dl VISEP Trial-

19. Delta Glucose Intervention vs Control Leuven I 50 mg / dL VISEP39 mg / dL Glucontrol28 mg / dL

20. Severe Hypoglycemia (< 40 mg / dL) with Different Infusion Protocols Leuven I - (Surgical) 5.1% Leuven 2 (Medical) 19% Glucontrol (Med / Surg) 8.6% VISEP (Medical) 17% Yale (Surgical) 0% Yale (Medical) 4.3% Glucommander (Surgical) 2.6% Van Den Berghe G, et al. N Engl J Med. 2001:345:1359; Van Den Berghe G, et al. N Engl J Med. 2006;354:449-461; Brunkhorst et al, N Engl J Med 358:125-39, 2008 Goldberg PA, et al. Diabetes Care. 2004;27:461; Goldberg PA, et al. J Cardiothorac Vasc Anes. 2004;18:690; Davidson PC. Diabetes Care. 2005;28:2418.

21. Infusion Protocols – Variable Hypoglycemia Rates

22. Comparison of Insulin Infusion Protocols in the ICU: Computer-Guided Versus Standard Column-Based Insulin Regimens CHRISTOPHER A. NEWTON, DAWN SMILEY, PAUL DAVIDSON, BRUCE BODE, DENNIS STEED, SOL JACOBS, ABBAS E. KITABCHI, FRANKIE STENTZ, ANGEL TEMPONI, PATRICK MULLIGAN,GUILLERMOE. UMPIERREZ, Atlanta, GA, Memphis, TN 2008 ADA Abstract

23. Summary Recent Insulin Infusion Studies Recent negative studies –Glucontrol, VISEP Caveats –Used Leuven protocol (viewed as suboptimal) –Delta Glucose less than desirable –Very high hypoglycemia rates seen in these studies….3 x hypoglycemia rate seen in U.S. NICE – SUGAR out soon

24. Infusion Insulin Take Home Points Surgical Populations easier Protocols vary greatly Automated protocols promising Need to monitor control and hypoglycemia < 5% of patients w/ glucose < 40 mg / dL is a reasonable goal Optimal glycemic target debatable Different targets for different groups? Where are you at?

25. “The days if ignoring blood sugar levels or tolerating marked hyperglycemia in the ICU (which was common place) are over.” Malhotra, NEJM 354:516, 2006

26. Transitions

27. Transition from Infusion Insulin Ramos, Childers, Maynard – SHM Abstract N = 41

28. Nurse Mandated Transition from IV insulin to SC Basal Bolus Insulin Criteria for Transition : History of diabetes HbA1c >6% Methodology: Glargine SC given at HS POD #1 if able to eat IV insulin discontinued at noon POD#2 post am meal insulin Davidson, Bode et al, May 2008 JDST pub pending

29. 0 12 24 36 48 60 hours SubQ Basal-Bolus Glucommander Managed by Anesthesiology in Operating Room Transition to SubQ

30. Last GM LunchDinnerBedtime 3:00AM Breakfast Lunch Dinner Bedtime 3:00AMBreakfast Lunch Dinner Bedtime 3:00AM Breakfast Blood Glucose (mg/dl) Hours after IV insulin Transition from Glucommander to Basal-Bolus Insulin Glargine and Aspart Basal: Multiplier * 500; CIR: 0.5 / Multiplier; Correction Factor: 1.7 / Multiplier n=209 Davidson, Bode et al, May 2008 JDST pub pending

31. Transition from infusion insulin Take Home Points Transition is opportunity for failure Protocols can / should address this Insulin multiplier method safe / effective Comparisons of transition methods needed Patients with stress hyperglycemia do OK without transition to basal - bolus regimen

32. More Evidence for Clinical Inertia Retrospective Analysis Teaching hospital (200 bed; metro. Phoenix) LOS 3 or more days; non-ICU 2,916 / 7,361 discharges with DM or HG diagnosis Average age 69 yrs; 90% white ALOS 5.7 days Cook CB, et al JHM 2007; 2:203-211

33. Not much movement…. First 24 hrs Last 24 hrs Stay Cook CB, et al. J Hosp Med 2007; 2: 203-211

34. Insulin dosing Δ insulin dose from first to last 24hr period 54% (n=1680) increased (avg 17 units) 39% decreased (avg 12 units) 7% no change Heterogeneous patterns of change within tertiles Increase in dose with rising hyperglycemia 1 st tertile 41% on more insulin by d/c 3 rd tertile 65% on more insulin; 31% less by d/c Cook CB, et al. J Hosp Med 2007; 2: 203-211

35. Conclusions Glycemic control poor Suboptimal use of insulin even when sustained hyperglycemia present (clinical inertia) Education should focus on importance of inpatient BG control and provide guidelines on how and when to change hyperglycemia therapy Cook CB, et al. J Hosp Med 2007; 2: 203-211

36. RCTs with demonstrating convincing benefit of TGC on general med – surg wards:

38. 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 Jackson Memorial Hospital, Miami Randomized Basal Bolus versus Sliding Scale Regular Insulin Therapy in patients with type 2 Diabetes (RABBIT-2 Trial)

39. 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) Smiley & Umpierrez, Southern Med J, June 2006 (RABBIT-2 Trial) Basal / Bolus arm

40. Mean Blood Glucose Levels During Insulin Therapy * p<0.01 ¶ p<0.05 ¶ * * * ¶ ¶ ¶ Day 3: P=0.06 Umpierrez, Diabetes Care 30: 2007

41. Blood Glucose Levels in Patients Who Failed SSRI: Transition to Basal Bolus Insulin Failure was defined as 3 consecutive BG values > 240 mg/dL during SSRI ¶ P: NS P: 0.02 ¶ ¶ ¶ ¶ Umpierrez, Diabetes Care 30: 2007

42. RABBIT 2 Improved glycemic control with basal / bolus insulin regimen compared to SSRI Subset that failed with SSRI controlled with basal / bolus No difference in hypoglycemia Umpierrez, Diabetes Care 30: 2007

43. Improving Glycemic Control in Medical Inpatients: A Pilot Study Implement SC Insulin Protocol on Med Service n = 89 Monitor acceptance and effect on hypoglycemia, insulin use, glycemic control Compare to prior observational study n = 91 Trujillo et al with JL Schnipper JHM 3:1 55-64

44. Results Resident acceptance poor - 56% Reluctant to start and adjust BaselineProtocol p Basal insulin 49% 64% 0.05 Nutritional insulin 0% 13% <0.001 Any hypoglycemia 7% 13% 0.20 ns Glycemic control not significantly improved If you build it, will they come?

45. Effect of Structured Insulin Orders and an Insulin Management Algorithm 400 bed academic center All adult monitored stays on Med / Surg wards with dx of DM or Documented Hyperglycemia n = 9,314 > 7 readings n = 5,530 What is effect of implementing a structured insulin order set? What is the incremental effect of an insulin management protocol? Outcomes –Insulin Use Patterns –Glycemic Control –Hypoglycemia Maynard et al, JHM publication pending 2008

46. Glucometrics % with patient-stays that are “uncontrolled” –day-weighted mean glucose ≥ 180 mg /dL % of patient-days that are “uncontrolled” –% of patient-days when mean glucose ≥ 180 mg /dL % of patient-stays / patient-days with hypoglycemia / severe hypoglycemia Pearson chi-square statistic to compare: –TP 1 (Baseline) Nov ’02 – Oct ’03 –TP2 (Order Set) Nov ‘03 – Apr ’05 –TP3 (Algorithm) May ’05 – Dec ’05

47. The Use of Basal Insulin Increases (sliding scale only regimens decline) 72% of 477 insulin regimens SSI only in May-Oct 2003 vs 26% of 499 in Mar-Aug 2004

48. % of 9,314 Patient-Stays with Uncontrolled Hyperglycemia

49. A Win / Win Situation 5,530 patients with DM or Hyperglycemia and > 7 POC Glucose readings TP3:TP1 RR Uncontrolled Patient-Day 0.77 (0.74 - 0.80) RR Uncontrolled Patient-Stay 0.73 (0.66 - 0.81) RR Hypoglycemic Patient-Day 0.68 (0.59 – 0.80) RR Hypoglycemic Patient-Stay 0.77 (0.64 – 0.92) Maynard et al, JHM publication pending 2008

50. Hypoglycemia

51. Hypoglycemia in Hospitalized Patients Treated with Antihyperglycemic Agents Setting: 675 bed university hospital 2,174 monitored patients received glucose lowering agents in 3 months 206 (9.5%) had one or more BG < 60 within 48 hrs of Rx with antihyperglycemic agent 484 hypoglycemic events (44% more than one event) 29% in DM 1 23% in ICU 72% in those Rxd with insulin alone Varghese P, et al. J Hosp Med. 2007; 2:234-240)

52. Hypoglycemic severity 20 (4%) with hypoglycemia-related adverse event; mean BG was 43mg/dl 10 (2%) serious with seizure or LOC 464 episodes with no adverse event; mean BG 50.9 mg/dl Varghese P, et al. J Hosp Med. 2007; 2:234-240)

53. Precipitating factors Etiologic factor % of hypo cases Reduction in enteral intake 40 Insulin adjustment 6.1 Steroid withdrawal 0.4 Unclear 43 “Diverse causes” 10.4 Medication error none Varghese P, et al. J Hosp Med. 2007; 2:234-240)

54. Antihyperglycemic Rxs 48 hrs prior to hypoglycemia Episodes on insulin Rx 78% (362/484) If on insulin - SSI alone 10.5% (38/362) SSI plus drip or basal 45.0% (163/362) Insulin with no SSI 44.5% (161/362) Orals alone 10.9% (Glyburide 19.1%, p<.01) Insulin alone 10.0% Orals plus insulin 7.9% Varghese P, et al. J Hosp Med. 2007; 2:234-240)

55. Hypoglycemia follow-up 1/3 with documented BG rechecked within 60 minutes < 50% with documented euglycemia within 2 hours of low Average time to documented resolution was 4 hrs, 3mins (median 2 hrs, 25mins) Varghese P, et al. J Hosp Med. 2007; 2:234-240)

56. Provider Response to Insulin-Induced Hypoglycemia in Hospitalized Patients To evaluate changes in treatment after hypoglycemia Retrospective data analysis of those treated with D50 for hypoglycemia; assessed by 2 diabetes specialists 52 subjects Garg, et al. J Hosp. Med. 2007; 2:258-260

57. Results Timing mean BG range 24 hrs prior hypo 137.5 + 57.0 63-287 Time D50 Rx 52.1+ 9.3 31-68 Changes in DM Rx % Endo agrees Insulin held for hypo 100 100% Change in insulin Rx 40 52% No change in Rx 52 32% Garg, et al. J Hosp. Med. 2007; 2:258-260

58. UCSD- Hypoglycemia Study Patients with glu < 60 mg / dL65 < 40 mg / dL8 % Any mismatch49.2 % with Documentation71% Harm documented 2 minutes until next glucose127 mean (med 60) minutes until nl glu259 mean (med 180)

59. Cases n = 65Controls n = 65 Age58 56 Male42% 60% Hillcrest72% 86% DM 19.2% 4.6% Liver Dz4.6% 13.9% Kidney Dz35.4% 16.9% CHF38.5% 15.4% Low / Lean BMI48% 25% Prior Hypoglycemia51% 8% Mismatch49% 32%

60. Non-critical care SC Insulin and Hypoglycemia: Take Home Points Suboptimal response to hyper- and hypo- glycemia is the rule –Nurses and physicians Opportunities for prevention of hypoglycemia often missed 2% of monitored inpatients - LOC / seizures Need more studies / prevention SC insulin protocols promoting basal / bolus regimens can achieve improved control safely --- hypoglycemia can even be reduced.

61. Transition out of the Hospital

62. Control at home and admission HbA 1C Home regimen prior to admission Admission reason: Hypoglycemia, Acute MI, Related to hyperglycemia (DKA, HHS, etc.) Physical limitations New co-morbidities that may limit prior oral therapy Hypoglycemia risk factors Treatment goals (I.e. hospice) Frequency of self monitoring Financial $$$$ Factors Used for Selecting Discharge Therapy for Patients with Known Diabetes

63. Adjusting home regimen using HbA1c HgbA1c <7 STEP 1:Lifestyle intervention and Metformin HgbA1c >9 Intensive Insulin + Metformin +/- Glitazone HgbA1c 7-8: Add basal insulin -Most effective Add Sulfonylurea -least expensive Add Glitazone -no hypoglycemia HgbA1c 8-9: Intensify insulin Add Insulin Add Glitazone or sulfonylurea New contraindication to therapy STEP UP therapy if needed No Yes Restart home regimen Adapted from “Management of Hyperglycemia in Type 2 Diabetes: A consensus Algorithm for the initiation and Adjustment of Therapy”. Diabetes Care Aug 2006 + 2007 AACE inpatient glycemic control resouce room

64. Published on-line May 21, 2007

65. Nissen’s Meta-analysis of Rosiglitazone Meta-analysis of 42 trials Inclusion criteria: –Duration >24 weeks –Randomized control group –Outcome data for myocardial infarction (MI) or death from cardiovascular (CV) causes A total of 15,560 patients were randomly assigned to receive rosiglitazone and 12,283 patients received a comparator The studies used included 5 studies submitted to the Food and Drug Administration’s approval hearing for rosiglitazone in 1999. DREAM and ADOPT were also included. Nissen SE, Wolski K. N Engl J Med. 2007;356:2457-2471.

66. Nissen SE & Wolski K. Effect of Rosiglitazone on the Risk of Myocardial Infarction and Deeath from Cardiovascular Causes. N Engl J Med 2007; 356 (www.nejm.org, accessed 5/21/07)www.nejm.org † IGT/IFG patients *all-cause death, OR=1.18 (0.89-1.55, P=0.24) Rosiglitazone & Cardiovascular Risk Study (N=42)RosiglitazoneControl OR (95% CI) P MI Small trials44 / 10,280 (0.43%)22 / 6105 (0.36%)1.45 (0.88-2.39)0.15 DREAM*15 / 2635 (0.57%)9 / 2634 (0.34%)1.65 (0.74-3.68)0.22 ADOPT27 / 1456 (1.85%)41 / 2895 (1.44%)1.33 (0.80-2.21)0.27 Overall1.43 (1.03-1.98)0.03 CV Death* Small trials25 / 6557 (0.38%)7 / 3700 (0.19%)2.40 (1.17-4.91)0.02 DREAM † 12 / 2365 (0.51%)10 / 2634 (0.38%)1.20 (0.52-2.78)0.67 ADOPT2 / 1456 (0.14%)5 / 2854 (0.18%)0.80 (0.17-3.86)0.78 Overall1.64 (0.98-2.74)0.06

67. Nissen SE & Wolski K. Effect of Rosiglitazone on the Risk of Myocardial Infarction and Deeath from Cardiovascular Causes. N Engl J Med 2007; 356 (www.nejm.org, accessed 5/21/07)www.nejm.org † IGT/IFG patients *all-cause death, OR=1.18 (0.89-1.55, P=0.24) Study (N=42)RosiglitazoneControl OR (95% CI) P MI Small trials44 / 10,280 (0.43%)22 / 6105 (0.36%)1.45 (0.88-2.39)0.15 DREAM*15 / 2635 (0.57%)9 / 2634 (0.34%)1.65 (0.74-3.68)0.22 ADOPT27 / 1456 (1.85%)41 / 2895 (1.44%)1.33 (0.80-2.21)0.27 Overall86 / 14,371 (0.60%)72 / 11,634 (0.62%)1.43 (1.03-1.98)0.03 CV Death* Small trials25 / 6557 (0.38%)7 / 3700 (0.19%)2.40 (1.17-4.91)0.02 DREAM † 12 / 2365 (0.51%)10 / 2634 (0.38%)1.20 (0.52-2.78)0.67 ADOPT2 / 1456 (0.14%)5 / 2854 (0.18%)0.80 (0.17-3.86)0.78 Overall39 / 10,378 (0.38%)22 / 9188 (0.24%)1.64 (0.98-2.74)0.06 Rosiglitazone & Cardiovascular Risk

68. 3.0 2.0 Odds Ratio 1.0 1.5 1.64 † 1.43 * Nissen SE, Wolski K. N Engl J Med. 2007;356:2457-2471. Nissen Meta-analysis of Rosiglitazone: Overall Rates of MI and CV Death *P=0.03; † P=0.06. Myocardial infarction Cardiovascular death

69. Limitations of This Meta-Analysis No access to actual data – therefore, no time to events calculation, no confirmation of events, no combined analyses (i.e. some subjects may have had both MI and death) Of 42 studies, only 11 peer reviewed, 26 never published Very small number of events Most trials of short duration Trials not designed to capture or adjudicate events

70. Published on-line June 5, 2007 RECORD Trial N Engl J Med. 2007 Jul 5;357(1):28-38

71. Summary Top Summary Author & Article Info References

72. JAMA 2007;298:1189-1195 September 12, 2007

73. JAMA 2007;298:1180-1188. September 12, 2007

74. Center for Drug Evaluation and Research Joint Meeting of the Endocrinologic and Metabolic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee July 30, 2007

75. Conclusions TZDs are associated with increased CHF No evidence of increased death with TZDs Unclear whether or not there is any association with myocardial ischemia or other CVD end points Meta-analyses are extremely difficult to interpret

76. “Black Box” Warning Thiazolidinediones (TZDs), including ACTOS & Avandia, cause or exacerbate congestive heart failure (CHF) in some patients. After initiation of ACTOS & Avandia and after dose increases, observe patients carefully for signs and symptoms of heart failure (including excessive rapid weight gain, dyspnea, and/or edema). If these signs and symptoms develop, the heart failure should be managed according to current standards of care. Furthermore, discontinuation or dose reduction of ACTOS & Avandia must be considered. ACTOS & Avandia) are not recommended in patients with symptomatic heart failure. Initiation of ACTOS & Avandia in patients with established NYHA Class III or IV heart failure is contraindicated. November 2007: The use of Avandia in patients treated with insulin and nitrates is contraindicated.

77. Dueling Press Releases ACCORD and ADVANCE ACCORD 10,251 patients with risk factors and DM Intensive control arm to A1c < 6 257 deaths A1c target 7 – 7.9 203 deaths Trial halted, press release sent out ADVANCE 11,000 patients with risk factors and DM Intensive control arm to A1c < 6.5 Press release - not in our study!

78. Selecting Discharge Therapy Take Home Messages Once A1C is >8.5% additional oral agents are unlikely to achieve goals Insulin at bedtime with or without oral agents is a good initial strategy Cost is heavily dependent on testing Elderly – hypoglycemia risk Hypoglycemia risk Glyburide > Glipizide Glitazones – in spite of imperfect evidence - be hesitant to start de novo Tailor glycemic target to individual

79. Regulatory / Public Reporting TJC SCIP UHC AHA IHI

80. Inpatient DM Resources http://www.aace.com/resources/igcrc/ http://www.hospitalmedicine.org/ResourceRoomRedesign/GlycemicCon trol.cfm

81. www.hospitalmedicine.org

82. Improving Care of the Hospitalized Patient with Hyperglycemia and Diabetes - from the SHM Glycemic Control Task Force JHM Supplement The Case for Supporting Inpatient Glycemic Control Programs Now: The Evidence and Beyond Braithwaite et al Management of Diabetes and Hyperglycemia in the Hospital: A Practical Guide to Subcutaneous Insulin Use in the Non-Critically Ill Adult Patient Wesorick et al Subcutaneous Insulin Order Sets and Protocols:Effective Design and Implementation Strategies Maynard et al Designing and Implementing Insulin Infusion Protocols and Order Sets Ahmann et al Bridge Over Troubled Waters: Safe and Effective Transitions of the Inpatient with Hyperglycemia O’Malley et al SHM Glycemic Control Task Force Summary: Practical Recommendations for Assessing the Impact of Glycemic Control Efforts. Schnipper et al Practical Strategies for Developing the Business Case for Hospital Glycemic Control Teams Magee et al