Muscle Microvascular Dysfunction in Central Obesity Is Related to Muscle Insulin Insensitivity but Is Not Reversed by High-Dose Statin Treatment

OBJECTIVE—To test the hypotheses that decreased insulin-mediated glucose disposal in muscle is associated with a reduced muscle microvascular exchange capacity (Kf) and that 6 months of high-dose statin therapy would improve microvascular func-tion in people with central obesity. RESEARCH DESIGN AND METHODS—We assessed skeletal muscle microvascular function, visceral fat mass, physical activ-ity levels, fitness, and insulin sensitivity in skeletal muscle in 22 female and 17 male volunteers with central obesity whose age (mean SD) was 51 9 years. We tested the effect of atorvastatin (40 mg daily) on muscle microvascular function in a randomized, double-blind, placebo-controlled trial lasting 6 months. RESULTS—Kf was negatively associated with a measure of glycemia (A1C; r 0.44, P 0.006) and positively associated with insulin sensitivity (the ratio of insulin-stimulated glucose effectiveness, or M value, to the mean insulin concentration, or I value; r 0.39, P 0.02). In regression modeling, A1C, visceral fat mass, and M:I explained 38 % of the variance in Kf (in a linear regression model with Kf as the outcome [