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Stan Schwartz MD, FACP, FACE Private Practice, Ardmore Obesity Program

The Obesity/Diabetes Epidemic: Adiposopathy & Obesity- The New Disease! Dx & (Rx) of Insulin Resistance & early DM Part 4. Stan Schwartz MD, FACP, FACE Private Practice, Ardmore Obesity Program Cardiometabolic Diabetes Center and Affiliate,.

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Stan Schwartz MD, FACP, FACE Private Practice, Ardmore Obesity Program

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  1. The Obesity/Diabetes Epidemic:Adiposopathy & Obesity- The New Disease!Dx & (Rx) of Insulin Resistance & early DMPart 4 Stan Schwartz MD, FACP, FACE Private Practice, Ardmore Obesity Program Cardiometabolic Diabetes Center and Affiliate,

  2. Obesity, IRS, Type 2 Diabetes and Atherosclerotic Disease • Obesity carries with it increase CV Risk Factors • Risk factors for macrovascular disease accrue before the diagnosis of diabetesas> 50% of patients with newly diagnosed Type 2 diabetes have pre-existing cardiovascular disease. • 2-4 fold > risk of ASVD in diabetic vs. normal patients • Cardiovascular disease causes 80% of all diabetic mortality- 75% coronary, 25% cerebral vascular • Type 2 diabetes is associated with an increased risk of morbidity and mortality from cerebrovascular disease versus the general population, and > HgA1c, >risk

  3. Outline • Epidemiology and Economics of obesity/diabetes • Perspectives on Obesity • Consequences of Obesity, Prediabetes, Obesity • Obesity/ Diabetes Risk Factors, • Obesity/ Diabetes Onset can be Prevented or Delayed – Early Risk Identification and Intervention. • Medical Benefits to Weight Loss • Treatment-CDC’s diabetes prevention program and other Evidence-Based Interventions- • Basics, • Next Lecture in Series

  4. Obesity leads to Prediabetes and Diabetes Mellitus-Type 2

  5. Each unit increase in BMI (about 2.7 - 3.6 kg) increases Type 2 diabetes risk by 12.1 percent 68 - 72 % of diabetes risk in the U.S. is attributable to or associated with excess weight For every kilogram increase in weight over 10 years, Type 2 diabetes risk increases 4.5 % Ford et al. Amer J Epidemiol 146:214,1997

  6. 93.2 Men Women 100 75 54.0 42.1 40.3 Age-Adjusted Relative Risk 50 27.6 21.3 15.8 8.1 11.6 5.0 6.7 4.3 25 2.9 2.2 4.4 1.5 1.0 1.0 1.0 0 23–23.9 <22 <23 24–24.9 25–26.9 27–28.9 29–30.9 31–32.9 33–34.9 35+ Body Mass Index (kg/m2) Relationship Between BMI and Risk of Type 2 Diabetes Mellitus Chan J et al. Diabetes Care 1994;17:961. Colditz G et al. Ann Intern Med 1995;122:481.

  7. Obesity, Insulin Resistance, Metabolic Syndrome and the Natural History of Type 2 Diabetes Age 0-15 15-40+ 15-50+ 25-70+ Envir.+ Other Disease Genes Macrovascular Complications Obesity (visceral) Poor Diet Inactivity IR phenotypeAtherosclerosisobesityhypertensionHDL,TG, HYPERINSULINEMIA Endothelial dysfunctionPCO,ED Disability Insulin Resistance MICVAAmp pp>7.8mM DEATH IGT – OMINOUS OCTET Type II DM 8 mechanisms of hyperglycemia  Beta Cell Secretion EyeNerveKidney BlindnessAmputationCRF Disability ETOHBPSmoking Risk of Dev. Complications Microvascular Complications

  8. Genes that Cause or are Associated with Diabetes Insulin Secretion Neonatal KCNJ11/Kir6.2 ABCC8/Sur1 Insulin MODY HNF-1α,1β, 4 α Glucokinase PDX1/IPF1 Neurod1/Beta2 KLF11 CEL Mitochondrial diabetes Type 2 CDKAL1 TCF7L2 HHEX/IDE SLC30A8/ZNT8 WFS1 NOTCH2-ADAM30 Insulin action Insulin receptor PPARG PHENOTYPE- eg: age of presentation, IFG/ IGT/Both/ severity depends on number of which kind of genes a person inherits – GENOTYPE Obesity FTO MCR4 Unknown IGFBP2 CDKN2A/B KIF11 JAZF1 CDC123-CAMK1D TSPAN8-LGR5 THADA ADAMTS9 NOTCH-ADAM30 Modified from McCarthy, NEJM 363:24,2339.

  9. Obesity, Insulin Resistance, Metabolic Syndrome and the Natural History of Type 2 Diabetes Age 0-15 15-40+ 15-50+ 25-70+ Envir.+ Other Disease Genes Macrovascular Complications Obesity (visceral) Poor Diet Inactivity IR phenotypeAtherosclerosisobesityhypertensionHDL,TG, HYPERINSULINEMIA Endothelial dysfunctionPCO,ED Disability Insulin Resistance MICVAAmp pp>7.8 DEATH IGT – OMINOUS OCTET Type II DM 8 mechanisms of hyperglycemia  Beta Cell Secretion EyeNerveKidney BlindnessAmputationCRF Disability Risk of Dev. Complications ETOHBPSmoking Microvascular Complications

  10. - - - 1.Pancreatic insulin secretion 5.Gut carbohydrate absorption 2.Pancreatic glucagon secretion Peripheral glucose uptake Hepatic glucose production ‘Ominous Octet: Pathophysiological Contributions to Hyperglycemia in Type 2 Diabetes ? ‘Nonet’- Gut Biome 7.Brain- Inc. Appetite Insulin Resistance, Decrease , GLP-1 8.Kidney- HYPERGLYCEMIA 3.Muscle 4.Liver 6.Fat- increased lipolysis, inc FFA

  11. Genes Genes Insulin resistance- lipotoxicity b-cell dysfunction/ Failure; dec. mass ± Environment ± Environment IFG IGT Glucose Toxicity Glucose Toxicity Type 2 diabetes Type 2 Diabetes: Two Principal Defects; Overview Abn. first peripheral hepatic 1st & 2nd Interactions will NOT occur if B-cells not genetically predisposed Reaven GM. Physiol Rev. 1995;75:473-486 Reaven GM. Diabetes/Metabol Rev. 1993;9(Suppl 1):5S-12S; Polonsky KS. Exp Clin Endocrinol Diabetes. 1999;107 Suppl 4:S124-S127.

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