Diabetes, Obesity, and Metabolism
Diabetes, Obesity, and Metabolism
Diabetes and obesity are profound risk factors for the development of premature coronary artery disease. In adults, diabetes is typically a result not of insufficient insulin but of insulin resistance. Mechanisms responsible for the well established relationship between obesity and insulin resistance remain obscure. Our research is designed to elucidate biochemical mechanisms underlying insulin resistance, characterize signaling pathways involved in its genesis, delineate consequences of insulin resistance that result in accelerated and premature coronary artery disease, and identify effective therapeutic interventions that can ameliorate cardiovascular manifestations and retard or preclude their development. The research utilizes transgenic mice genetically rendered insulin resistant and atherogenic as well as patients with syndromes of insulin resistance including type 2 diabetes. It focuses on links between insulin resistance, diabetes, the coagulation system, platelets, the fibrinolytic system, and fat storage in visceral, subcutaneous, hepatic, and other sites. Novel pharmacologic agents designed to diminish insulin resistance and ameliorate diabetes and its consequences are being evaluated in multicenter studies – some supported by industry and others by the National Institutes of Health.
Recent Grant Support
NIH: (U01 HL61744) “BARI 2D” - 1/01-12/07
Kathryn Detre, Principal Investigator, Pratley, Co-Investigator
Representative Publications
Weyer C, Tataranni PA, Bogardus C, Pratley RE. Insulin resistance and insulin secretory dysfunction are independent predictors of worsening of glucose tolerance during each stage of type 2 diabetes development. Diabetes Care 2001; 24:89-94.
Weyer C, Wolford JK, Hanson RL, Foley JE, Tataranni PA, Bogardus C, Pratley RE. Subcutaneous abdominal adipocyte size, a predictor of type 2 diabetes, is linked to chromosome 1q21-q23 and is associated with a common polymorphism in LMNA in Pima Indians. Mol Genet Metab 2001; 72:231-238.
Pratley RE, Weyer C. The role of impaired early insulin secretion in the pathogenesis of type 2 diabetes mellitus. Diabetologia 2001; 44:929-945.
Weyer C, Hanson K, Bogardus C, Pratley RE. Long-term changes in insulin action and insulin secretion associated with weight gain, loss, regain and maintenance of body weight. Diabetologia 2000; 43:36-46.
Weyer C, Foley JE, Bogardus C, Tataranni PA, Pratley RE. Enlarged subcutaneous abdominal adipocyte size, but not obesity itself, predicts Type II diabetes independent of insulin resistance. Diabetologia 2000; 43:1498-1506.
Weyer C, Bogardus C, Mott DM, Pratley RE. The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus. J Clin Invest 1999; 104:787-794.
Weyer C, Bogardus C, Pratley RE. Metabolic characteristics of individuals with impaired fasting glucose and/or impaired glucose tolerance. Diabetes 1999; 48:2197-2203.
Pratley RE, Weyer C, Bogardus C. Metabolic abnormalities in the development of type 2 diabetes mellitus. In LeRoith D, Taylor SI, Olefsky JM, eds., Diabetes Mellitus: A Fundamental and Clinical Text, 2nd Edition. Lippincott Williams & Wilkins, Philadelphia, 1999.
Pratley RE, Thompson DB, Prochazka M, Baier L, Mott D, Ravussin E, Sakul H, Ehm MG, Burns DK, Foroud T, Garvey WT, Hanson RL, Knowler WC, Bennett PH, Bogardus C. An autosomal genomic scan for loci linked to prediabetic phenotypes in Pima Indians. J Clin Invest 1998; 101:1757-1764.
Pratley RE. Gene-environment interactions in the pathogenesis of type 2 diabetes mellitus: lessons learned from the Pima Indians. Invited Review, Proc Nutr Soc 1998; 57:175-181.
