Diabetic Heart Disease
Diabetic Heart Disease
Type 2 diabetes is a silent killer afflicting 10,000,000 Americans. 7,000,000 more are afflicted but unaware that they have the disease. Many millions more have insulin resistance, a common precursor of type 2 diabetes. The risk for development of coronary artery disease is 2- to 4-fold greater and the risk of cardiac events of a lethal nature subsequently higher when diabetes is present. Insulin resistance even without diabetes increases coronary risk.
Illustration: A theoretical explanation.
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.
Recent Grant Support
Grant Title: Cardiomyopathy in Diabetes
Sponsor: National Institutes of Health
Co-Investigator: Dr. Burton E. Sobel; Dr. Martin M. LeWinter (PI)
Grant Title: Inflammation, Procoagulation, & Plaque Vulnerability
Sponsor: National Institutes of Health
Pl: Dr. Burton E. Sobel
Grant Title: BARI 2D - Fibrinolysis and Coagulation Core
Sponsor: National Institutes of Health
PI: Dr. Burton E. Sobel
Grant Title: Pioglitazone on Plaque Vulnerability
Sponsor: Takeda Pharmaceuticals North America, Inc.
PI: Dr. Burton E. Sobel
Representative Publications
Schneider DJ, Sobel BE: Augmentation of synthesis of plasminogen activator inhibitor type-1 by insulin and insulin-like growth factor type-1 and its pathogenetic implications for diabetic vascular disease. Proc. Natl. Acad. Sci. USA 88:9959-9963, 1991.
McGill JB, Schneider DJ, Arfken CL, Lucore CL, Sobel BE: Factors responsible for impaired fibrinolysis in obese subjects and NIDDM patients. Diabetes 43:104-109, 1994.
Sobel BE, Woodcock-Mitchell J, Schneider DJ, Holt RE, Marutsuka K, Gold H: Increased plasminogen activator inhibitor type-1 in coronary artery atherectomy specimens from type 2 diabetic compared with nondiabetic patients: A potential factor predisposing to thrombosis and its persistence. Circulation 97:2213-2221,1998.
Kruszynska Y, Yu JG, Sobel BE, Olefsky JM: Effects of troglitazone on blood concentrations of plasminogen activator inhibitor 1 in patients with type 2 diabetes mellitus and in lean and obese normal subjects. Diabetes 49:633-639, 2000.
Wadsworth MP, Sobel BE, Schneider DJ, Taatjes DJ: Delineation of the evolution of compositional changes in atheroma. Histochem Cell Biol 118:59-68, 2002.
Cefalu WT, Schneider DJ, Carlson HE, Migdal P, Lim LG, Izon MP, Kapoor A, Bell-Farrow A, Terry JG, Sobel BE: Effect of combination glipizide GITS/metformin on fibrinolytic and metabolic parameters in poorly controlled, type 2 diabetic subjects. Diabetes Care 25:2123-2128, 2002.
Sobel BE, Neimane D, Mack WJ, Hodis HN, Buchanan TA: The ratio of PAI-1 activity to the concentration of PAI-1 protein in diabetes: Adding insult to injury. Coron Artery Dis 13:275-281, 2002.
Sobel BE: Effects of glycemic control and other determinants on vascular disease in type 2 diabetes. Am J Med 113:12S-22S, 2002.
Sobel BE, Frye R, Detre KM: Burgeoning dilemmas in the management of diabetes and cardiovascular disease: Rationale for the BARI 2D trial. Circulation 107:636-642, 2003.
Furumoto T, Fujii S, Onozuka H, Zaman AKMT, Goto D, Sugawara T, Mikami T, Watanabe S, Abe K, Terauchi Y, Kadowaki T, Sobel BE, Kitabatake A: Persistance of induction of cardiomyopathic effects by insulin resistance despite loss of insulin receptor substrate-1 signaling. Circulation, in press.
