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

Abstract

Objective. To test the hypotheses that decreased insulin mediated glucose disposal in muscle is associated with a reduced muscle microvascular exchange capacity and that 6 months of high dose-statin therapy would improve microvascular function in people with central obesity.

Methods & Results. We assessed skeletal muscle microvascular function, visceral fat mass, physical activity levels, fitness and insulin sensitivity in skeletal muscle, in 22 female and 17 male volunteers with central obesity whose mean (SD) age 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. Microvascular exchange capacity (Kf) was negatively associated with a measure of glycaemia (HbA_1c) (r=−0.44, p=0.006); and positively associated with insulin sensitivity (M/I) (r=0.39, p=0.02). In regression modelling, HbA_1c, visceral fat mass and M/I explained 38% of the variance in Kf [in a linear regression model with Kf as the outcome (R² =0.38, p=0.005)]. M/I was associated with Kf independently of visceral fat mass (B coefficient 3.13, (95%CI 0.22, 6.02), p=0.036). Although 6 months treatment with atorvastatin decreased LDLc by 51%, p<0.001 and plasma C reactive protein (hsCRP) by 75% p=0.02, microvascular function was unchanged.

Conclusions. Decreased insulin-mediated glucose uptake in skeletal muscle is associated with impaired muscle microvascular exchange capacity, independently of visceral fat mass. Muscle microvascular function is not improved by 6 months of high dose statin treatment, despite marked statin-mediated improvements in lipid metabolism and decreased inflammation.