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.

Our work focuses on mechanisms responsible for the acceleration and lethality of coronary artery disease resulting from diabetes or insulin resistance alone. It involves the generation and use of transgenic mice, quantitative cellular imaging of vessel walls, and clinical research focusing on modification of insulin sensitivity. The objective is identification of therapeutic targets that when modified pharmacologically will permit retardation and possibly prevention of coronary disease accompanying insulin resistance and diabetes.