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Diabetes: What’s New? What’s Next?

Diabetes: What’s New? What’s Next?. Robert P. Hoffman, M.D. Grand Rounds June 1, 2007. Introduction.

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Diabetes: What’s New? What’s Next?

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  1. Diabetes:What’s New?What’s Next? Robert P. Hoffman, M.D. Grand Rounds June 1, 2007

  2. Introduction • Frederick Allen 1919 “The knowledge of diabetes is advancing rapidly enough that even the patient whose outlook seems darkest should take courage to remain alive in the hope of a treatment that can be called curative” • 1921 Banting and Best at the University of Toronto discovered insulin

  3. DCCT • 1993 • 1441 subjects (age 13-35) randomized to intensive versus conventional therapy • Intensive diabetes therapy markedly reduces risk of long term complications in adults and adolescents • Increased risk of severe hypoglycemia • Did not tell us how to achieve good control

  4. What’s New?, What’s Next? • New insulins • New modes of delivery • New tecnology • Curative treatments • Prevention

  5. New Insulins

  6. Zn Insulin Structure

  7. Normal Insulin Regular Lispro Aspart Glulysine Glucose 0 1 2 3 4 5 Time Hours Short Acting Insulins

  8. NPH/Lente Levomir Glargine Long Acting Insulins INSULIN 0 4 8 12 16 20 24 Time Hours

  9. Zn pH =4 pH =7.4 Glargine

  10. FFA FFA FFA Levomir

  11. Intensive Insulin Regimens Glargine Levomir Lispro Lispro Lispro Bf Lu Su Bt

  12. Insulin Adjustment Bed Morn Lunch Supper LP LP LP Gla

  13. Intensive Insulin Regimens Lispro Lispro Lispro NPH BF Lu Su Bt

  14. Intensive Insulin Regimens Lispro Lispro NPH NPH BF Lu Su Bt

  15. Intensive Insulin Adjustment Bed Morn Lunch Supper N LP LP N

  16. Advantages of New Insulins • Better post prandial glucose control • Less nocturnal hypoglycemia • Better schedule flexibility • No major differences in overall glucose control

  17. Inhaled Insulin

  18. Inhaled Insulin • Action profile similar to lispro • Well tolerated by subjects • Still need to take long acting • Need to work out dosing differences • Small decrease in lung diffusion capacity • Long term safety unknown

  19. New Technology

  20. Continuous Glucose Monitoring

  21. Maia and Arau´jo; Diab Res Clin Pract 2007,

  22. Wilson et al, Diabetes care 2007

  23. Change from baseline at 1 and 3 months of AIC. Values are means SE. P values correspond to the difference in change from baseline between the continuous and control groups. F, continuous group (arm 1); f, biweekly group (arm 2); OE, control group. Deis et al Diabetes Care 2006

  24. Insulin Pumps

  25. Continuous Subcutaneous Insulin Infusion (CSII)

  26. Insulin Pumps MiniMed

  27. Infusion Sets

  28. Results

  29. Adolescents and Pumps White et al Diabetes 2000

  30. Randomized Adult Tsui et al, Diabetes Care 2001

  31. Randomized school age adolescents • Garcia-Garcia J Ped Endo Metab 2007 • At 24 months randomized study MDI versus CSII • Hemoglobin A1c was 7.70 +/- 0.64% vs 7.54 +/- 0.74% (p = 0.8); • Body mass index SDS was 0.33 +/- 0.74 vs 0.40 +/- 1.01 (p = 0.9); • Total daily insulin requirements were 0.95 +/- 0.10 vs 1.05 +/- 0.18 U/kg (p = 0.4), • Incidence of severe hypoglycemia was 0.00 +/- 0.00 vs 0.04 +/- 0.14 episodes/patient/year (p = 0.8); and • Incidence of ketoacidosis was 0.20 +/- 0.27 vs 0.04 +/- 0.14 episodes/patient/year (p = 0.2).

  32. Preschool Children Wilson et al Diabetes Care 2005 Fox et al Diabetes Care 2007

  33. Hypoglycemia

  34. DKA-Metaanalysis Eggar Diabetic Medicine 1997

  35. Advantages to CSII • Effectively treats “dawn” phenomenon • Adjust basal rate at 3 AM • No shots • Bolus for snacks without extra shot • Flexibility of meals, exercise and travel • Decreased need for snacks

  36. Disadvantages to SCII • Requires more time/effort • Contact sports, swimming, bathing can be difficult • Increased risk of DKA

  37. Cure

  38. Pancreas Transplant • Successful • 95% one year survival • 70% one year insulin free • Problems • Life long immunosuppression • Donor availability • Indications • Renal failure or near renal failure • Combined pancreas kidney

  39. Islet Transplantation

  40. Results • Insulin free for 4 to 12 months • Normal hemoglobin A1c • Near normal glucose profiles • No complications • Problems • 2 cadaver pancreases per patient • Harvesting technique critical • Required immunosuppression

  41. Autologous Bone Marrow Transplant

  42. Complications

  43. Prevention • Diabetes Prevention Trial Type 1 • First degree relatives type 1 diabetic patients • High Risk-received subcutaneous insulin • No effect • Intermediate Risk-oral insulin ongoing enrollment • No effect • European Nicotinamide Diabetes Intervention Trial • No effect

  44. TrialNet • Series of multicenter studies to prolong beta cell function or prevent type 1 diabetes • Prolong beta cell function • Anti CD3 • Anti CD20 • Anti CD3 plus GLP-1 agonist • Oral insulin

  45. Conclusion • The knowledge of diabetes is advancing rapidly enough that all patients should work to maintain the best possible glycemic control to prevent complications now and in the future with the hope of new technologies and treatments that will make their task and lifestyle easier if not eliminate the disease all together.

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