The Obesity/Diabetes Epidemic: Perspectives, Consequences, Prevention, Treatment Part 5 Stan Schwartz MD, FACP, FACE Private Practice, Ardmore Obesity Program Cardiometabolic Diabetes Center and Affiliate, Main Line Health System Emeritus, Clinical Associate Professor University of Pennsylvania
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
Obesity leads to Prediabetes and Diabetes Mellitus-Type 2
Each unit increase in BMI (about 2. 7 - 3 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
Relationship Between BMI and Risk of Type 2 Diabetes Mellitus Age-Adjusted Relative Risk Body Mass Index (kg/m2) <23 24–24.9 25–26.9 27–28.9 33–34.9 25 50 75 100 1.0 2.9 4.3 5.0 8.1 15.8 27.6 40.3 54.0 93.2 <22 23–23.9 29–30.9 31–32.9 35+ 1.5 2.2 4.4 6.7 11.6 21.3 42.1 Men Women The risk of diabetes increases with increasing BMI values in men and women [1,2]. Moreover, the age-adjusted relative risk for diabetes begins to increase at BMI values that are considered normal for men (24 kg/m2) and women (22 kg/m2) based on mortality risk. The marked increase in the prevalence of obesity is an important contributor to the 25% increase in the prevalence of diabetes in the United States over the last 20 years [3]. Increases in abdominal fat mass, weight gain since young adulthood, and a sedentary lifestyle are additional obesity-related risk factors for diabetes [1,4,5]. 1. Colditz GA, Willett WC, Rotnitzky A, Manson JE. Weight gain as a risk factor for clinical diabetes mellitus in women. Ann Intern Med 1995;122:481-486. 2. Chan JM, Rimm EB, Colditz GA, et al. Obesity, fat distribution, and weight gain as risk factors for clinical diabetes in men. Diabetes Care 1994;17:961-969. 3. Harris MI, Flegal KM, Cowie CC, et al. Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S. adults. The Third National Health and Nutrition Examination Survey, 1988-1994. Diabetes Care 1998;21:518-524. 4. Ohlson LO, Larsson B, Svardsudd K, et al. The influence of body fat distribution on the incidence of diabetes mellitus. Diabetes 1985;34:1055-1058. 5. Helmrich SP, Ragland DR, Leung RW, Paffenbarger Jr RS. Physical activity and reduced occurrence of non-insulin-dependent diabetes mellitus. N Engl J Med 1991;325:147-152. Chan J et al. Diabetes Care 1994;17:961. Colditz G et al. Ann Intern Med 1995;122:481.
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 IRS/Metabolic Syndrome Obesity HypertensionHDL,TG, Ins. Res.,HYPERINSULINEMIA Endothelial Dysfunction, Atherosclerosis PCO,ED Disability Insulin Resistance MI CVA Amp ppg>140 (7.8mM) IGT Type 2 DM DEATH -Cell Secretion Blindness Amputation CRF Eye Nerve Kidney Risk of Complications ETOH BP Smoking Disability Microvascular Complications
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.
The Adipocytokine Syndrome: A New Model for Insulin Resistance and ß-Cell Dysfunction Atherothrombosis Liver Artery CRP, PAI-1 FFA, TNFa, IL-6 Angiotensinogen, PAI-1 FFA, TNFa Obesity IR Diabetes ASVD Adiponectin Adiponectin FFA Visceral fat cells Resistin, TNFa Leptin Sns FFA, TNFa, Leptin Muscle Brain Pancreas
prediabetes
Impaired Glucose Tolerance is Highly Prevalent Among Obese Youth Normal GTT Impaired GTT Diabetes Age 11–18 y 75% 21% 4% Age 4–10 y 75% 25% Although the prevalence of type 2 diabetes is increasing, only a small percentage of obese children have this disease. However, impaired glucose tolerance is highly prevalent in obese children and adolescents. Among a multiethnic cohort of 167 children and adolescents recruited from a pediatric obesity clinic, about 25% had abnormal glucose tolerance tests, and 4 of 112 adolescents had frank diabetes [1]. Those with impaired glucose tolerance had higher BMI than those with normal glucose tolerance. Impaired glucose tolerance was present in Hispanic, non-Hispanic black, and non-Hispanic white children. 1. Sinha R, Fisch G, Teague B, et al. Prevalence of impaired glucose tolerance among children and adolescents with marked obesity. N Engl J Med 2002;346:802-810. GTT: glucose tolerance test Sinha et al. N Engl J Med 2002;346:802.