1. DIABETES MELLLITUS Strategies for Achieving Control in an Office Setting

2. Type 2 Diabetes

3. Global Prevalence of Diabetes Projected to More Than Double by 2030

4. Prevalence of Overweight/Obesity* in NHANES 2003-2004, by Sex and Age†

5. Total Prevalence of Diabetes in Americans Aged =20 Years by Age Group (2005)

6. Number of Newly Diagnosed Cases of Diabetes by Age Group in the US (2005)

7. Greater Prevalence of Diabetes in Certain Ethnic Populations in the US (2005)

8. Burden on Healthcare System

9. Diabetes Reduces Lifespan

10. Risk Reduction for Key Endpoints with Intensive Therapy (UKPDS)

11. Tight Glycemic Control Reduces Incidence of Microvascular Complications

12. Intensive Glycemic Control in Type 2 Diabetes Reduces Risk of Complications (UKPDS)

13. Tight Glycemic Control Reduces Long-Term Cardiovascular Risk (DCCT/EDIC Study)

14. Current Treatment Goals for Glycemic Control

15. Glycemic Goals Are Not Being Met

16. Most Patients with Type 2 Diabetes Also Do Not Achieve Risk-Factor Control

17. Mechanism of Postprandial Hyperglycemia: Glucose Production

18. Mitrakou A, et al. N Engl J Med. 1992;326:22-29. Glucose Glucagon Impaired Glucagon Suppression in IGT

19. Mitrakou A, et al. N Engl J Med. 1992;326:22-29. Insulin Glucagon Impaired Glucagon Suppression in IGT 20 25 30 35 40 45 -60060120180240300 Time (min) Glucagon (pmol/L) NGT IGT

20. Impaired Glucagon Suppression in Type 2 Diabetes Müller WA, et al. N Engl J Med. 1970;283:109-115. Glucose Glucagon

21. Impaired Glucagon Suppression in Type 2 Diabetes Müller WA, et al. N Engl J Med. 1970;283:109-115. Insulin Glucagon

22. TYPE 1 DIABETES 15% of the total INSULIN DEPENDENCE v REQUIRING GLUCAGON SUPPRESSION

23. TYPE 2 DIABETES INVOLVES 2 PRIMARY PATHOGENETIC MECHANISMS –PROGRESSIVE DECLINE IN BETA CELL MASS AND FUNCTION ASSOCIATED WITH THE LACK OF GLUCAGON SUPPRESSION –THE PRESENCE OF A RESISTANCE TO INSULIN ACTION AT THE TISSUE LEVEL

24. ISSUES TO DEAL WITH AWARENESS EDUCATION IMPLEMENTATION OF TREATMENT

25. TREATMENT OPTIONS FOOD EXERCISE ORAL PARENTERAL BETA CELL FUNCTION GLUCAGON SUPPRESSION INSULIN RESISTANCE

26. TREATMENT OPTIONS ORAL –SECRETAGOGUES SULFONYLUREAS NONSULFONYLUREAS –INSULIN RESISTANCE THIAZOLIDINEDIONES (TZD) METFORMIN –GLUCAGON SUPPRESSION INCRETINS (INtestinal SECRETION of Insulin) –JANUVIA –STARCH BLOCKERS ACARBOSE

27. TREATMENT OPTIONS PARENTERAL –SUBCUTANEOUS INCRETIN MIMETICS INSULIN –TRANSPULMONARY

28. TREATMENT OPTIONS ORAL –SECRETAGOGUES SULFONYLUREAS NONSULFONYLUREAS –INSULIN RESISTANCE THIAZOLIDINEDIONES (TZD) METFORMIN –GLUCAGON SUPPRESSION INCRETINS (INtestinal SECRETION of Insulin) –JANUVIA –STARCH BLOCKERS ACARBOSE

29. TREATMENT OPTIONS ORAL ORAL –SECRETAGOGUES SULFONYLUREAS –GLYBURIDE –GLIPIZIDE –GLIMEPIRIDE (LONG ACTING) NONSULFONYLUREAS –NATEGLINIDE (STARLIX) –REPAGLINIDE (PRANDIN)

30. TREATMENT OPTIONS ORAL ORAL –INSULIN RESISTANCE THIAZOLIDINEDIONES (TZD) –PIOGLITAZONE (ACTOS) –ROSIGLITAZONE (AVANDIA) METFORMIN

31. TREATMENT OPTIONS ORAL ORAL –GLUCAGON SUPPRESSION INCRETINS (GLP-1) –SECRETED BY THE L-CELLS OF THE DISTAL ILEUM –CIRCULATES TO THE PANCREAS –STIMULATES INSULIN SECRETION –INHIBITS GLUCAGON SECRETION

32. TREATMENT OPTIONS ORAL GLUCAGON SUPPRESSION –INCRETINS (GLP-1)---”GLIP-ONE” THERE ARE NO ORAL INCRETINS –BUT THERE IS AN ORAL WAY TO HELP NATURALLY OCCURRING INCRETINS GLIPTINS (DPP-4 INHIBITORS) –SITAGLIPTIN (JANUVIA) –VILDAGLIPTIN (GALVUS -not yet released)

33. Synthesis, Secretion, and Metabolism of GLP-1 and GIP

34. DPP-4 Degrades GLP-1

35. TREATMENT OPTIONS PARENTERAL INCRETIN MIMETICS –DIRECT STIMULATION OF INSULIN –DIRECT INHIBITION OF GLUCAGON Exenatide (BYETTA) Amylin (SYMLIN) –NOT DEGRADED BY DPP-4 LONG-ACTING

36. TREATMENT OPTIONS PARENTERAL –SUBCUTANEOUS INCRETIN MIMETICS INSULIN –TRANSPULMONARY INSULIN

37. INSULIN THERAPY LONG ACTING ANALOGUES –LANTUS –LEVEMIR RAPID ACTING ANALOGUES –HUMALOG –NOVOLOG –APIDRA

38. INSULIN THERAPY MIXTURES –75/25 HUMALOG MIX –70/30 NOVOLOG MIX

39. INSULIN THERAPY IS INSULIN INEVITABLE ?

40. b-Cell Function Declines Regardless of Intervention in Type 2 Diabetes

41. AVAILABLE INSULINS

42. INSULINONSETPEAKDURATION HUMALOG< 30 minutes30-90 minute< 90 minutes

43. AVAILABLE INSULINS INSULINONSETPEAKDURATION HUMALOG< 30 minutes30-90 minute< 90 minutes NOVOLOG< 15 minutes1-3 hours3-5 hours

44. AVAILABLE INSULINS INSULINONSETPEAKDURATION HUMALOG< 30 minutes30-90 minute< 90 minutes NOVOLOG< 15 minutes1-3 hours3-5 hours REGULAR30-60 min2-4 hours6-12 hours

45. AVAILABLE INSULINS INSULINONSETPEAKDURATION HUMALOG< 30 minutes30-90 minute< 90 minutes NOVOLOG< 15 minutes1-3 hours3-5 hours REGULAR30-60 min2-4 hours6-12 hours NPH1-2 hours4-14 hours10-24 hours

46. AVAILABLE INSULINS INSULINONSETPEAKDURATION HUMALOG< 30 minutes30-90 minute< 90 minutes NOVOLOG< 15 minutes1-3 hours3-5 hours REGULAR30-60 min2-4 hours6-12 hours NPH1-2 hours4-14 hours10-24 hours LENTE1-3 hours6-16 hours12-24 hours

47. AVAILABLE INSULINS INSULINONSETPEAKDURATION HUMALOG< 30 minutes30-90 minute< 90 minutes NOVOLOG< 15 minutes1-3 hours3-5 hours REGULAR30-60 min2-4 hours6-12 hours NPH1-2 hours4-14 hours10-24 hours LENTE1-3 hours6-16 hours12-24 hours ULRALENTE4-8 hours10-30 hours18-36 hours

48. NEWER INSULINS INSULINONSETPEAKDURATION NOVOLOG MIX 70/30 < 15 min1-4 hours12-24 hours HUMALOG MIX 75/25 <30 min2-4 hours6-12 hours LANTUS1 hourNONE24 hours LEVEMIR1 hourNONE24 hours

49. NEWER INSULINS INSULINS ONSET PEAKDURATION APIDRA<15 minutes1-2 hour3-4 hours

50. THERAPEUTIC GOALS  HbA1C as low as possible  REDUCE BASAL HYPERGLYCEMIA  Provide a basal amount of insulin  REDUCE POSPRANDIAL EXCURSIONS  Supplemental insulin with the meal

52. REDUCING BASAL HYPERGLYCEMIA  NPH bid  LANTUS qd  LEVEMIR qd  INSULIN PUMP w  HUMALOG  NOVOLOG  APIDRA METFORMIN AMARYL BYETTA JANUVIA TZD

53. REDUCE POSTPRANDIAL GLUCOSE HUMALOG NOVOLOG APIDRA BYETTA STARLIX PRANDIN JANUVIA

54. TREATMENT STRATEGIES FOR SIGNIFICANTLY ELEVATED HbA1C –GET THE FBS DOWN FIRST –AS THE HbA1C DECLINES THE POST-PRANDIAL GLUCOSES PLAY A GREATER ROLE

55. TREATMENT STRATEGIES FOR FASTING GLUCOSE  NPH bid  LANTUS q HS  LEVEMIR q HS METFORMIN AMARYL BYETTA JANUVIA

56. TREATMENT STRATEGIES FOR POST PRANDIAL GLUCOSES APPROACH WITH RAPID ACTING INSULIN –TWO ISSUES DETERMINE THE PPG CARB CONTENT OF THE MEAL PRE-MEAL GLUCOSE LEVEL

57. TREATMENT STRATEGIES FOR POST PRANDIAL GLUCOSES CARB CONTENT CORRECTION –1 unit for every (15 grams) carbs consumed 1:15 carb ratio PRE MEAL GLUCOSE CORRECTION 1 Unit drops FS 50 mg%

58. TREATMENT STRATEGIES FOR POST PRANDIAL GLUCOSES CHOOSE A TARGET FOR CORRECTION e.g., 100 mg% FORMULA combines CORRECTION + CARBS FS CORRECTION + CARB RATIO = TOTAL (FS-target)/50 + 1:15 = TOTAL

59. SAMPLE COMPUTATION Patient has a 60 gm CHO meal –Uses 1 unit for 15 gm 4 units Patient has a target of 120 mg% –Correction factor = 40 (1 unit drops 40mg%) Current FS is 240 –Will need 3 units (FS-target)/40 + 4 units for carbs (240-120) = 120/4 =3 units for FS

60. SUMMARY –TYPE 2 DIABETES IS MULTIFACTORIAL –GO AFTER FBS FIRST METFORMIN GLIMEPIRIDE hs LEVEMIR or LANTUS –MEALTIME CONTROL NATEGLINIDE or REPAGLINIDE EXENATIDE JANUVIA RAPID ACTING INSULIN ANALOGUES

61. SUMMARY DIET and EXERCISE –Cannot be emphasized more