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Diabetes Mellitus 101 for Medical Professionals

Diabetes Mellitus 101 for Medical Professionals. An Aggressive Pathophysiologic Approach to Cardiometabolic Therapy for Type 2 Diabetes :. Part 6. Stan Schwartz MD,FACP Clinical Associate Professor of Medicine, U of Pa. Cardiometabolic Institute Penn-Presbyterian Hospital, UPHS.

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Diabetes Mellitus 101 for Medical Professionals

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  1. Diabetes Mellitus 101 for Medical Professionals An Aggressive Pathophysiologic Approach to Cardiometabolic Therapy for Type 2 Diabetes: Part 6 Stan Schwartz MD,FACP Clinical Associate Professor of Medicine, U of Pa. Cardiometabolic Institute Penn-Presbyterian Hospital, UPHS

  2. Problems for animals in the wild

  3. Modern Insulin Resistant Man “Locked” IntoSeasonal Insulin Resistance Syndrome Physiology (Neuroendocrinology; Winter Condition All Year Long) Insulin resistance begets insulin resistance: hyperinsulinemia in hypothalamus reduces nutrient sensing via increased NE/5HT, overcoming normal spring rise in dopa/decreasing dopa in spring ADAPTIVE Insulin Resistance MAL-ADAPTIVE Insulin Resistance Cincotta AH. et al. Taylor and Francis, Eds Hansen, B Shafrir, E London. 2002. 271-312. Meier AH, Cincotta AH et al. Diabetes Reviews. 1996. 4(4):464-86.

  4. The Biologic Clock Integrator of Signals Uses DOPAMINE SCN Summer Winter Low Dopa Set PM-Winter High IR High Sympathetic tone Persistent High Dopa Set AM-Summer Low IR Low Sympathetic tone Maladaptive Hyperglycemia, high fat/sugar diets, altered sleep/wake cycles, no exercise, stress patients with genetically susceptible b-cell Diabetes Mellitus Afferent signals to SCN that maintain low dopa set include 1. persistent hyperglycemia, 2. high fat/ high sugar diet, 3. no exercise 4. altered sleep/ wake cycle, 5. stress

  5. Bromocryptine QR: Proposed mechanism of action Morning administration (within 2 hours of waking) of AGENT Low dopaminergic tone in hypothalamus in early morning in diabetes Restoration of morning peak in dopaminergic activity (via D2 receptor-mediated activity) Corrects • Sympathetic tone • HPA axis tone •  Hepatic gluconeogenesis •  FFA and TG •  Insulin resistance •  Inflammation/hypercoagulation • Sympathetic tone • HPA axis tone •  Hepatic gluconeogenesis •  FFA and TG • Insulin resistance • Inflammation/hypercoagulation Decreased postprandial glucose levels Reduction in insulin resistance Day-long reduction in plasma glucose, TGs and FFAs Impaired glucose metabolism, hyperglycemia and insulin resistance Adverse cardiovascular pathology Fonseca. Use of Dopamine agonists in Type-2-Diabetes. Oxford American Pocket Cards. OUP, 2010 Cincotta. Hypothalamic role in Insulin Resistance and insulin Resistance Syndrome. Frontiers in Animal Diabetes Research Series. Taylor and Francis, Eds Hansen, B Shafrir, E London, pp 271-312, 2002 5

  6. Bromocriptine-QR (Cycloset) Dosing: Start with 0.8 mg (one tablet) within two hours of awakening in the AM. Increase weekly as tolerated to target dose of 1.6 to 4.8 mg upon awakening Holt RIG, et al. Diabetes, Obesity and Metabolism 12: 1048–57, 2010

  7. KM Curve – Fast-Acting Bromocryptine Safety Trial Cumulative Percent Composite CVD Endpoint HR 0.58; 95% CI, 0.35-0.96 RRR=42% *MI, Stroke, hospitalization unstable angina, hospitalization CHF, or coronary revasc. KM Curve: the separation in favor of Cycloset begins 3 months and persists through the end of the study Gaziano M. Diabetes Care 2010, March 23 online

  8. Colsevelam in Prediabetes Handelsman

  9. Effects of Colesevelam on A1C Levels in Add-On Therapy Trials: ≥0.50% Reductions GLOWS Week 12 Metformin Week 26 Sulfonylurea Week 26 Insulin Week 16 -0.10 -0.20 *P≤0.007 -0.30 n=>1,000 Mean Change in A1C(%) -0.40 -0.50 -0.50* -0.50* -0.54* -0.54* -0.60 Zieve FJ et al. Clin Ther. 2007;29:74.Bays H et al. Presented at: AACE 16th Annual Meeting & Clinical Congress; April 2007. Abstract 204.Fonseca VA et al. Presented at: AACE 16th Annual Meeting & Clinical Congress; April 2007. Abstract 409.Goldberg RB, Truitt K. Presented at: AHA Scientific Sessions; November 2006; Chicago, IL. Poster 1581.

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