3. Diabetes Management in the Hospital Bruce W. Bode, MD, FACE Atlanta Diabetes Associates Atlanta, Georgia

4. Diabetes in Hospitalized Patients 1997 3.5 Million US Hospitalizations 15% of Admissions 14 Million Hospital Days 20% of All Hospital Days 36% First Diagnosed in Hospital 66% No Documentation by Physician 27% Labeled Hyperglycemia 2% Diagnosed on Chart

5. Diabetes in Hospitalized Patients 1997 Costs $ 23,500 Each Diabetes Patient vs.$ 23,500 Each Diabetes Patient vs. $12,200 for Non-Diabetes Patient $12,200 for Non-Diabetes Patient 60% of All Diabetes-Related Costs60% of All Diabetes-Related Costs Only 5% DKA, HHNKCOnly 5% DKA, HHNKC 48% Diabetes Complications48% Diabetes Complications 52% Other Conditions52% Other Conditions

6. Diabetes in Hospitalized Patients Reason for Higher Costs l Higher Rate of Hospitalization l Longer Stays l More Procedures, Medications l Chronic Complications l More Arteriosclerotic Disease l More Infections l Complicated Pregnancies

7. Diabetes in Hospitalized Patients High-risk for Bacterial Infection –Surgery –Catheters –Intravenous Access –Anaesthesia Problems with wound healing Problems with tissue and organ perfusion

8. Infectionsin Diabetes Infections in Diabetes More Frequent l Bacteremia l Septic Shock l Pyelonephritis l Candida l TPN Unique l Necrotizing Fasciitis l Fournier’s Gangrene l Mucoromycosis l Emphysematous GB l Malignant External Otitis

9. Infections in Diabetes l One BG >220 mg/dl results in 5.8 times increase in nosocomial infection rate l Two hours hyperglycemia results in impaired WBC function for weeks Pomposelli, New England Deaconess, J Parenteral and Enteral Nutrition 22:77-81,1998

10. TPN In Diabetes VA Cooperative Trial l Benefit Negated l Increased Infections l Related to Hyperglycemia Buzby et al. NEJM 325:525-531, 1991

11. Side Effects of BG >200 mg/dl l Reduced Intravascular Volume l Dehydration l Electrolyte Fluxes l Impaired WBC Function l Immunoglobulin Inactivation l Complement Disabling l Increased Collagenase, Decreased Wound Collagen

12. Psychology of Diabetes in Hospital l Patients expect good glycemic control as part of hospital care l They strive for recommended goals at home l Difficult to understand staff’s casual approach to BG’s >150

13. Evidence for Immediate Benefit of Normoglycemia in Hospitalized Patients l Numerous Publications on in Vitro Evidence –Neutrophil Dysfunction –Complement Inhibition –Altered Redox State (Pseudohypoxia) –Glucose Rich Edema as Culture Media l Six Recent Clinical Publications supporting good glucose control in the hospital setting

14. Open Heart Surgery in Diabetes Portland St. Vincent Medical Center Control Group l N=968 l 1987-1991 l SubQ Insulin q 4 h l Goal 200 mg/dl l Standard Deviation 36 l All Mean BG’s <200 47% Study Group l l N=1499 l l 1991-1997 l l IV Insulin l l Goal 150-200 mg/dl l l Standard Deviation 26 l l All Mean BG’s <200 84% Furnary et al, The 34th Meeting of The Society of Thoracic Surgeons New Orleans, LA January 26, 1998

15. Open Heart Surgery in Diabetes Portland CII Protocol Demographics l Total Open Heart Surgery Patients 14,468 l Diabetes at Admission 2467 (17%) l Age 65 SD 10 l Males 62% l Insulin Rx 36% l OHA 48%

16. Open Heart Surgery in Diabetes Portland St. Vincent Medical Center Perioperative Blood Glucose Furnary et al, The 34th Meeting of The Society of Thoracic Surgeons New Orleans, LA January 26, 1998

17. Incidence of DSWI: 1987-1997 CII Furnary, et al, The 34th Meeting of The Society of Thoracic Surgeons New Orleans, LA January 26, 1998

18. Open Heart Surgery in Diabetes Portland CII Protocol Infectious Complications Diabetes l 31/2467 (1.3%) Deep Sternal Wound Infection (DSWI) 23/31 Required Second Admission 22 Micrococcus 0 Anaerobes, fungal, yeast 0 Anaerobes, fungal, yeastNon-Diabetes l 40/12,005 (0.3%)

19. Open Heart Surgery in Diabetes Portland CII Protocol Mortality l All(99/2467) 4.0% l SQI 6.1% l CII 3.0% l DSWI 19.0% l No DSWI 3.8% Recent Experience l 1994-1997 DSWI as in non-diabetics l 1996-7 No DSWI in last 15 mo.

20. Open Heart Surgery in Diabetes Portland CII Protocol Comparison of Groups Higher Risk Patients in CII Group

21. Open Heart Surgery in Diabetes Portland CII Protocol Univariate Analysis of DSWI

22. VariableSQICIISavings # DSWI2,96810091,959 Additional LOS47,48816,41631,342 Additional $$78.4M$26.6M$51.7M # Deaths564192372 Estimated USA Socioeconomic Savings Assumes 742K cases*, 20% prevalence of DM & 2% DSWI with SQI *1998 Heart & Stroke Statistical update, AHA

23. Open Heart Surgery in Diabetes Portland CII Protocol Weakness of Study l Not Randomized l Temporal Sequential Nature l Subtle Cumulative Improvements in Techniques

24. Open Heart Surgery in Diabetes Portland CII Protocol Conclusions l Magnitude and Strength of Study is Compelling l Ethics of Confirming Study Would be Questionable l Application of CII is Simple and Safe l Hyperglycemia Predicts DSWI l CII Prevents DSWI

25. Open Heart Surgery in Diabetes John Hopkins l Prospective Cohort Study of 411 OHS pts with Diabetes 1990 – 1995 l Diabetes based on history (42% insulin treated, 45% oral agents) l SMBG 4x/day with sliding scale l Measured relationship between peri-operative control and risk of all infections

26. Open Heart Surgery in Diabetes John Hopkins l 24.3% with infections l BG divided into quartiles Relative Odds Q1 121-206 20.1% Q2 207-229 21.6% 1.17 Q3 230-252 29.8% 1.86* Q4 252-352 25.7% 1.72* Golden SH Diabetes Care 22: 1408, 1999 * P < 0.01

27. DIGAMI Study Diabetes, Insulin Glucose Infusion in Acute Myocardial Infarction(1997) l Acute MI With BG > 200 mg/dl l Intensive Insulin Treatment l IV Insulin For > 24 Hours l Four Insulin Injections/Day For > 3 Months l Reduced Risk of Mortality By: 28% Over 3.4 Years 51% in Those Not Previous Diagnosed Malmberg BMJ 1997;314:1512

28. Cardiovascular Risk Mortality After MI Reduced by Insulin Therapy in the DIGAMI Study Malmberg, et al. BMJ. 1997;314:1512-1515. All Subjects (N = 620) Risk reduction (28%) P =.011 Standard treatment 0.3.2.4.7.1.5.6 01 Years of Follow-up 2345 Low-risk and Not Previously on Insulin (N = 272) Risk reduction (51%) P =.0004 IV Insulin 48 hours, then4 injections daily 0.3.2.4.7.1.5.6 01 Years of Follow-up 2345 6-11

29. ICU Survival l 1548 Patients (mostly OHS pts.) l All with BG >200 mg/dl l Randomized into two groups –Maintained on IV insulin –Conventional group (BG 180-200) –Intensive group (BG 80-110) l Conventional Group had 1.74 X mortality Van den Berghe et al, NEJM 2001;345(19):1359

30. ICU IV Insulin Protocol l If > 100 mg/dl, 2 U/h If > 200 mg/dl, 4 U/h l If > 140 mg/dl, increase by 1 – 2 U/h l If 121 to 140 mg/dl, increase by 0.5 – 1 U/h l If 111 to 120 mg/dl, increase by 0.1 – 0.5 U/h l If 81 to 110 mg/dl, no change l If 61 to 80 mg/dl, change back to prior rate Van den Berghe et al, NEJM 2001;345(19):1359

31. ICU Survival Blood glucose control: Convetional Intensive Mean AM BG 153 103 % Receiving Insulin 39% 100% BG < 40 mg/dl 6 39 Van den Berghe et al, NEJM 2001;345(19):1359 In no instance was hypoglycemia considered to be a serious event

32. ICU Survival Intensive Therapy (80 to 110 mg/dL) resulted in: l 34% reduction in mortality l 46% reduction in sepsis l 41% reduction in dialysis l 50% reduction in blood transfusion l 44% reduction in polyneuropathy Van den Berghe et al, NEJM 2001;345(19):1359

33. Conclusion All hospital patients should have normal glucose

34. Insulin The agent we have to control glucose only most powerful

35. Comparison of Human Insulins / Analogues Insulin Onset ofDuration of preparations action Peak action Regular30–60 min2–4 h6–10 h Lispro/aspart5–15 min1–2 h 4–6 h NPH/Lente1–2 h4–8 h10–20 h Ultralente2–4 hUnpredictable16–20 h Glargine1–2 hFlat~24 h

36. 4:00 25 50 75 8:0012:0016:0020:0024:004:00 BreakfastLunchDinner Plasma insulin (U/ml) Plasma insulin ( µ U/ml) Time 8:00 Physiological Serum Insulin Secretion Profile

37. 4:0016:0020:0024:004:00 BreakfastLunchDinner 8:00 12:008:00 Time Glargine or Detemir Lispro Lispro Lispro Aspart Aspart Aspart or Plasma insulin Basal/Bolus Treatment Program with Rapid-acting and Long-acting Analogs

38. Methods For Managing Hospitalized Persons with Diabetes l Continuous Variable Rate IV Insulin Drip Major Surgery, NPO, Unstable, MI, DKA, Hyperglycemia, Steroids, Gastroparesis, Delivery, etc l Basal / Bolus Therapy (MDI) when eating

39. Continuous Variable Rate IV Insulin Drip l Mix Drip with 125 units Regular Insulin into 250 cc NS l Starting Rate Units / hour = (BG – 60) x 0.02 where BG is current Blood Glucose and 0.02 is the multiplier l Check glucose every hour and adjust drip l Adjust Multiplier to keep in desired glucose target range (100 to 140 mg/dl)

40. Continuous Variable Rate IV Insulin Drip l 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 l If BG is < 80 mg/dL, Give D50 cc = (100 – BG) x 0.3 l Give continuous rate of Glucose in IVF’s l Once eating, continue drip till 1 hour post SQ insulin

41. Glucose Management System

42. Glucommander l Based on 15 Year Experience with a Computer Based Algorithm for the Administration of IV Insulin l Developed for Marketing by MiniMed and Roche l GMS System l Shelved Pending FDA Approval of IV Use of Insulin l Useful and Safe for Any Application of IV Insulin

44. Glucommander Effectiveness l Initial blood glucose –Median 292 mg/dl –Range 181-1,568 l Time to achieve glucose < 180 mg/dl –Median 3 hours –Range 0.3 - 19.7 l Time to achieve three consecutive glucose results between 60 - 180 mg/dL –Median 3. 1 hours –Range 0.3 - 22.5

45. Converting to SQ insulin l Establish Daily Insulin Requirement –IV Insulin First Night –(BG - 60) x Multiplier = Ins/hr Targeted to 120 –60 x Multiplier x 24 = Daily Insulin Requirement l Give One-Half Amount As Basal l Give p.c. Boluses Based on CHO Intake –Start at CHO/Ins 1 CHO = 1.5 units Rapid-acting l Monitor a.c. tid, hs, and 3 am l Supplement All BG >150 –(BG-100)/(1700/Daily Insulin Requirement)

46. Protocol for SQ Insulin in Hospitalized Patient l Bedtime: Wt (kg) x 0.2 = Units of Glargine l Meals Eaten: 1.5 units per 15 Gm CHO eaten l BG >150: (BG-100) / CF CF = 3000 / Wt (kg) l Do Not Use Sliding Scale Only l Any BG <80: D50 = (100-BG) x 0.3 ml Maintain INT l Do Not Hold Insulin When BG Normal

47. How to Initiate MDI l Starting dose = 0.4 to 0.5 x weight in kilograms l Bolus dose (aspart/lispro) = 20% of starting dose at each meal l Basal dose (glargine) = 40% of starting dose given at bedtime or anytime l Correction bolus = (BG - 100)/ Correction Factor, where CF = 1700/total daily dose

48. How to Initiate MDI l starting dose = 0.45 x wgt. in kg l Wt. is 80 kg; 0.45 x 80 = 36 units l Bolus dose (aspart / lispro) = 20% of starting dose at each meal; 0.2 x 36 = 7 units ac (tid) l Basal dose (glargine) = 40% of starting dose at HS; 0.4 x 36 = 14 units at HS l Correction bolus = (BG - 100)/ CF, where CF = 1700/total daily dose; CF = 50

49. Correction Bolus Formula Example: –Current BG:250 mg/dl –Ideal BG: 100 mg/dl –Glucose Correction Factor: 50 mg/dl Current BG - Ideal BG Glucose Correction factor 250 - 100 50 =3.0u

50. Piedmont Diabetes Plan What Can We Do For Patients Admitted To Hospital? l NPO Pathway For All Diabetes Patients l Finger Stick BG ac qid on ALL Admissions l Check All Steroid Treated Patients l Diagnose Diabetes FBG >126 mg/dl Any BG >200 mg/dl

51. Piedmont Diabetes Plan What Can We Do For Patients Admitted To Hospital? l Document Diagnosis in Chart Hyperglycemia Is Diabetes Until Proven Bring to All Physician’s Attention Note on Problem List and Face Sheet l Check Hemoglobin A1C l Hold Metformin; Hold TZD with CHF, Liver Dysfunction l Start Insulin in All Hospitalized Patients Not Already on Insulin

52. Piedmont Diabetes Plan What Can We Do For Patients Admitted To Hospital? l Get Diabetes Education Consult l Instruct Patient in Monitoring and Recording See That Patient Has Meter on Discharge l Decide on Case Specific Program for Discharge l Arrange Early F/U with PCP

53. Piedmont Diabetes Plan What Can We Do For Patients Admitted To Hospital? Piedmont Diabetes Plan What Can We Do For Patients Admitted To Hospital? l Follow Guidelines For Endocrinology Consult Any Hypoglycemia Requiring Intervention DKA or HHNC Patient on Insulin Pump Diabetes in Pregnancy Glucocorticoid Therapy in Diabetes Progressive Diabetes Complications A1C >8%, Microalbuminuria >30 mg

54. l Treat Any Patient With BG > 150 With Insulin –Treat Any BG >150 with Rapid-acting Insulin (BG-100) / (5000 / wt #) or (3000 / wt kg) –Treat Any Recurrent BG >200 with IV Insulin l If More than 0.5 u/hr IV Insulin Required with Normal BG Start Long Acting Insulin Protocol for Insulin in Hospitalized Patient

55. l Daily Total: Pre-Admission or Weight (#) x 0.2 u –40 % as Glargine (Basal) –60% as Rapid-acting insulin (Bolus) Give in Proportion to Meal’s CHO EatenGive in Proportion to Meal’s CHO Eaten l BG >150: (BG-100) / CF CF = 5000 / Wt(#) or 3000 / Wt(kg) l Do Not Use Sliding Scale As Only Diabetes Management

56. Protocol for Insulin in Hospitalized Patient Treatment of Hypoglycemia l Any BG <80 mg/dl: D50 = (100-BG) x 0.3 ml IV l Do Not Hold Insulin When BG Normal

57. Diabetes at Piedmont Hospital Conclusions l Any BG >200 mg/dl Is Diabetes (Fasting >126 mg/dl) l Most Diabetes Is Type 2 l All DM patients Must Self-Monitor BG’s and Record l No BG >150 mg/dl Should Go Untreated l Most Hospitalized DM [atients Should Be on Insulin l IV Insulin is Most Effective, Efficient, Safest Rx in Acute Illness (Glucommander)

58. Diabetes at Piedmont Hospital Conclusions 2 l Type 2 Diabetics Are Resistant to Insulin Reactions l Treat Insulin Reactions in Hospital With IV Glucose l Do Not Be Hold Insulin for Normal BG, i.e. 80-120 mg/dl l A1C Values >7% Indicates Sub-optimal Care

59. Diabetes at Piedmont Hospital Conclusions 3 l Discharge Plan For BG Control l You Are the Link Between the Best Diabetes Care and the Patient l Use Your Diabetes Resources Diabetes Education Center Endocrinologists

60. The Paradigm for the Millenium Hyperglycemia: A Mortal Sin A blood glucose over 200 in a hospitalized patient causes increased morbidity and mortality. In the 21st Century Neglecting a BG >200 Will Be Malpractice

61. Conclusion Intensive therapy is the best way to treat patients with diabetes

62. QUESTIONS l For a copy or viewing of these slides, contact l WWW.adaendo.com WWW.adaendo.com