Functional dilator capacity is independently associated with insulin sensitivity and age in central obesity and is not improved by high dose statin treatment.

OBJECTIVE: To test the hypothesis that: (i) functional microvascular dilator capacity is independently associated with insulin sensitivity and age in individuals with central adiposity at risk of cardiovascular disease (CVD); and (ii) functional microvascular dilator capacity is improved by high dose statin treatment. METHODS: Functional dilator capacity (measured as change in laser Doppler blood flux from baseline during post occlusive reactive hyperemia [peak flux%resting flux; PF%RF] and flowmotion (power spectral density [PSD] analysis)) were assessed in 40 people with central adiposity and one or more other CVD risk factors. Measurements were made at rest and during acute hyperinsulinaemia before and six months after high dose atorvastatin (40 mg daily) or placebo. RESULTS: Insulin-induced change in PF%RF was independently associated with insulin sensitivity (M/I) (r = 0.46 p = 0.02) and age (r = -0.46 p = 0.02), which together explained almost half of the variance in PF%RF (adjusted r² = 0.37, p = 0.008). Whilst atorvastatin decreased LDL cholesterol by 51% (p < 0.001), PF%RF and flowmotion remained unchanged. CONCLUSIONS: Insulin sensitivity and age are independently associated with an insulin-induced change in functional microvascular dilator capacity in individuals with central adiposity at risk of CVD. Dilator capacity is not improved by six months high dose statin treatment.

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 function in people with central obesity. RESEARCH DESIGN AND METHODS: 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 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 [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 LDL cholesterol by 51% (P < 0.001) and plasma high-sensitivity C-reactive protein 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 (Kf), 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.