Department of Internal Medicine - Research

Veterans Administration Medical Center and 
The Juvenile Diabetes Foundation

DIABETES RESEARCH CENTER (DRC)

Diabetes mellitus is a disease characterized by elevated levels of blood sugar and abnormalities of large and small blood vessels. The vascular abnormalities lead to complications affecting vision, kidney function, the nervous system and an increased frequency of heart attacks, stroke and peripheral vascular disease. One of the first vascular abnormalities noted in both Type I and Type II diabetes is an impairment in the ability of blood vessels to dilate appropriately, which is thought to lead to the more serious vascular diseases.

The Diabetes Research Center combines the talents of experienced clinical investigators, molecular biologists and vascular physiologists in an integrated, multidisciplinary approach toward the study and treatment of abnormalities of vascular reactivity which characterize diabetes mellitus. Specific measures are detailed for bringing basic research findings to rapid clinical investigation in patients with diabetes; conversely, the DRC is structured such that observations made in clinical trials can be dissected at the mechanistic level using animal models of diabetes and cultured vascular cells.

The Center consists of a Patient Core and six individual projects.

The Patient Core will be central to the performance of all clinical studies of the Center. This core will assume the direct role of recruiting study participants and implementing protocols.

Project 1 : Interaction of Insulin and Leptin in Regulating Nerve Activity and Vascular Reactivity. This project also examines the interactions of leptin and insulin in regulating body fat mass.

Project 2 : Mechanism of Altered Coronary Microvascular Reactivity in Humans with Diabetes. This project examines the mechanism of impaired human coronary arteriolar dilation in patients with diabetes, focusing on the role of reactive oxygen species which may quench endothelial derived nitric oxide.

Project 3 : Hyperglycemia, Insulin Resistance and Endothelial Function in Human Diabetes. This study tests the hypotheses that diabetes mellitus causes endothelial dysfunction through hyperglycemia and that this occurs through generation of free radicals. This multidisciplinary project utilizes the abilities of experienced investigators with expertise in human vascular function, invasive coronary physiology and clinical diabetes.

Project 4 : Mechanisms of Endothelium Dysfunction in Diabetes. Diabetes mellitus is associated with increased cardiovascular morbidity and mortality. This may, in part, be due to abnormalities of the vascular endothelium. The overall goal of this project is to evaluate the mechanisms responsible for impaired agonist mediated endothelium-dependent vascular responses in diabetes mellitus.

Project 5 : Circulating Factors in the Etiology of Diabetic Vascular Disease. This project studies the role of L-fucose, a sugar that is elevated in the serum of patients with diabetes, in the development of diabetic complications.

Project 6 : Role of IGF-I in Altered Endothelial Function and Vasodilation in Diabetes Mellitus. Insulin Like Growth Factor-I (IGF-I) has been demonstrated to dilate several blood vessels in humans and animals, in most studies being as potent, or more potent, than insulin in its ability to induce vascular relaxation or vasodilation. This project will evaluate the effects of low dose IGF-I treatment on endothelial function and blood flow in the forearm of patients with Type II diabetes.

DRC PROJECT AND CORE DIRECTORS

Administration