3080 Cat: Obesity, Metabolic Syndrome, and Type 2 Diabetes Mellitus

CARDIOVASCULAR MECHANISMS OF EXERCISE INTOLERANCE IN DIABETES AND THE ROLE OF SEX

J.G. Regensteiner1,2,4, M. Cree-Green1,3,4, D. Rafferty1,2, T.A. Bauer1,2,4,

J.E.B. Reusch1,2,4,5

1. University of Colorado School of Medicine, Aurora, Colorado, USA

2. Department of Medicine

3. Department of Pediatrics

4. Center for Women's Health Research

5. Veterans Administration Medical Center

Type 2 diabetes (T2D) is associated with decreased exercise capacity (EC). Decreased EC in T2D is important because it confers increased risk for premature mortality and may represent very early evidence of cardiovascular (CV) impairment. Our lab has identified cardiac and peripheral causes of the abnormalities but the relative importance of the various abnormalities has not been well integrated. Current data suggest preliminarily that the defect is greater in women than men with T2D. Our long-term goal is to understand the abnormalities and their greater presence in women, to develop strategies to restore EC and thereby improve CV health in T2D by understanding and targeting pathogenic drivers of this impairment. New MRI based non-invasive imaging offers a quantitative, sensitive and reproducible opportunity to define early pathogenic cardiac and vascular changes contributing to EC decrease in T2D. We have shown that

• EC impairment in T2D is associated with both cardiac and vascular dysfunction.

• EC and associated cardiac and vascular dysfunction are more pronounced in T2D women than men.

This collaborative research employs state of the art cardiac and vascular imaging, developed by our team, to quantitatively characterize CV systemic structure and function in men and women with T2D compared to non-diabetic controls. With these new methods, we are able to simultaneously integrate functional exercise capacity measurements with early cardiac and vascular structural and functional measurements. Understanding the cardiac and vascular abnormalities associated with EC may enable us to target novel therapeutic approaches.