466-P: Effect of Metformin on Cardiovascular Function in Type 1 Diabetes

Abstract

Cardiovascular (CV) disease remains the leading cause of mortality in type 1 diabetes (T1D) despite advances in glycemic control and to a greater extent than predicted by traditional CV risk factors. Metformin is generally thought to have vascular benefit in T2D and other insulin resistant states, though conclusive data for CV outcomes is lacking. In T1D metformin has been studied for glycemic control, but little attention has been paid to CV effects. We hypothesized that metformin would improve insulin sensitivity (IS), vascular function and compliance, and mitochondrial function in T1D. T1D participants (n=23) underwent a placebo-controlled, double-blind, random order, cross-over design intervention with 6 weeks of metformin vs. placebo. Glycemic control (CGM), cardiac function (echocardiography), vascular stiffness (Sphygmacor and Dynapulse), autonomic function, IS (hyperinsulinemic euglycemic clamp), and mitochondrial function in vivo (31P MRS) and ex vivo (muscle biopsy with high resolution respirometry) were measured after each phase. Glucose control and IS by clamp were not improved with metformin. Oxidative phosphorylation was increased in vivo, but ex vivo mitochondrial function was not improved. Cardiac contractility and output, arterial stiffness, systemic vascular resistance, and possibly autonomic function, were improved with metformin. These results suggest that metformin may provide CV benefit in T1D. Disclosure J. Abolarin: None. I.E. Schauer: Other Relationship; Spouse/Partner; Kestrel Labs. Funding National Institutes of Health