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Emerging Trends in Diabetes

Emerging Trends in Diabetes. Robert Lash, MD Professor of Internal Medicine University of Michigan Health System. 1994. 1995. 1996. 1997. 1998. 1999. 2000. 2001. 2002. 2003. 2004. 2005. 2006. 2007. 2008. 2009. 2010. What’s new in diabetes?.

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Emerging Trends in Diabetes

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  1. Emerging Trends in Diabetes Robert Lash, MD Professor of Internal Medicine University of Michigan Health System

  2. 1994

  3. 1995

  4. 1996

  5. 1997

  6. 1998

  7. 1999

  8. 2000

  9. 2001

  10. 2002

  11. 2003

  12. 2004

  13. 2005

  14. 2006

  15. 2007

  16. 2008

  17. 2009

  18. 2010

  19. What’s new in diabetes? • Recognizing that diabetes has a variety of ‘causes’, with treatments to match • New thinking about endpoints: Is lowering glucose enough? • A new medicine that does the wrong thing for the right reason • Finally, some real progress on the ‘artificial pancreas’

  20. Sulfonylureas (and insulin) Metformin Type 2diabetes Thiazolidinediones

  21. Glucose C 2009 ProteinLounge.com INSULIN PIP2 PIP3 Lipid Raft InsulinReceptor GLUT4 GLUT4Translocation lnsulin Receptor Pathway P P SHC GRB2 PIP2 PI3K SOS P Flotillin PIP3 IRS1 P P Crk Ras Nck P c-CbI GTP CAP Fyn ReceptorInternalization P Rab4 GRB10 P P GLUT4Vesicle Raf SHC IRS1/2 P P H+ P Insulin Degradation& ReceptorDephosphorylation APS PPtase1 H+ c-CbI P PDK ATP Citrate lyase P PKC P P Rac P MEKs P AktPKB EBS Translation Insulin Translation Anti-apoptosis Fatty AcidSynthesis GeneExpression TRE Gene Expression mTOR Insulin EAI ERKs EAI GlycogenSynthase BAD GSK3 p70S6K eIF4EBP FKHRL1 EEF2K P BAD JNK S6 eIF2B 14-3-3 EEF2 eIF4 Elk c-Jun c-Fos

  22. Sulfonylureas (and insulin) Metformin Type 2diabetes Thiazolidinediones GLP-I analogs & DPP IV inhibitors

  23. GLP-1release Gosh, I’m full! DPP-4 inhibitor DPP-4 enzyme Increased insulin secretion X Decreased glucagon secretion Inactive metabolites GLP-1Mechanisms of Action Reduced hepatic glucose output

  24. Sulfonylureas (and insulin) Metformin Type 2diabetes Thiazolidinediones GLP-I analogs & DPP IV inhibitors

  25. What’s new in diabetes? • Recognizing that diabetes has a variety of ‘causes’, with treatments to match • New thinking about endpoints: Is lowering glucose enough? • A new medicine that does the wrong thing for the right reason • Finally, some real progress on the ‘artificial pancreas’

  26. “Diabetes is a remarkable affliction, not very frequent among men… The course is the common one, namely, the kidneys and the bladder; for the patients never stop making water, but the flow is incessant, as if from the opening of aqueducts. “Moreover, life is disgusting and painful; thirst, unquenchable; excessive drinking, which, however, is disproportionate to the large quantity of urine, for more urine is passed; and one cannot stop them either from drinking or making water.”

  27. Chao EC and Herny RR. Nat Rev Drug Discov. 2010;9:551-559.

  28. Efficacy and safety of canagliflozin versus glimepiride inpatients with type 2 diabetes inadequately controlled withmetformin (CANTATA-SU): 52 week results from arandomised, double-blind, phase 3 non-inferiority trial Cefalu WT, Leiter LA, et. al.Lancet 2013; 382: 941–50

  29. Percent of patientswith hypoglycemia

  30. Sulfonylureas (and insulin) Metformin Type 2Diabetes Thiazolidinediones GLP-I analogs &DPP IV inhibitors SGLT2 inhibitors

  31. What’s new in diabetes? • Recognizing that diabetes has a variety of ‘causes’, with treatments to match • New thinking about endpoints: Is lowering glucose enough? • A new medicine that does the wrong thing for the right reason • Finally, some tangible progress on the ‘artificial pancreas’

  32. Threshold-Based Insulin-Pump Interruption for Reduction of Hypoglycemia Bergenstal RM, Klonoff DC, et. al.N Engl J Med 2013;369:224-32.

  33. Bergenstal RM, Klonoff DC, et. al.N Engl J Med 2013;369:224-32.

  34. Frequency and severity of hypoglycemia ‘Duration’ of hypoglycemic events Bergenstal RM, Klonoff DC, et. al.N Engl J Med 2013;369:224-32.

  35. What’s new in diabetes? • Recognizing that diabetes has a variety of ‘causes’, with treatments to match • New thinking about endpoints: Is lowering glucose enough? • A new medicine that does the wrong thing for the right reason • Finally, some tangible progress on the ‘artificial pancreas’

  36. Questions?

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