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 insulinmediated glucose disposal in muscle is associated with a reduced muscle microvascular exchange capacity (K f ) 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 Ϯ SD) was 51 Ϯ 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-K f was negatively associated with a measure of glycemia (A1C; r ϭ Ϫ0.44, P ϭ 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 ϭ 0.39, P ϭ 0.02). In regression modeling, A1C, visceral fat mass, and M:I explained 38% of the variance in K f (in a linear regression model with K f as the outcome [R 2 ϭ 0.38, P ϭ 0.005]). M:I was associated with K f independently of visceral fat mass (B coefficient 3.13 [95% CI 0.22-6.02], P ϭ 0.036). Although 6 months' treatment with atorvastatin decreased LDL cholesterol by 51% (P Ͻ 0.001) and plasma high-sensitivity C-reactive protein by 75% (P ϭ 0.02), microvascular function was unchanged.CONCLUSIONS-Decreased insulin-mediated glucose uptake in skeletal muscle is associated with impaired muscle microvascular exchange capacity (K f ), 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.

Impact of high dose n-3 polyunsaturated fatty acid treatment on measures of microvascular function and vibration perception in non-alcoholic fatty liver disease: results from the randomised WELCOME trial

“…Cutaneous MR was assessed on the ventral surface of the non-dominant forearm arm using laser Doppler fluximetry (Moor VMS LDF2 and DP1T probe; Moor Instruments, Axminster, UK) [27]. Blood flux was recorded continuously before and during the dilator response to transient ischaemia (180 mmHg for 3 min; MoorVMS-PRES).…”

Meeting Report

“…These data suggested attenuation in capacity for blood/tissue exchange in people with features of metabolic syndrome. Although statins are known to decrease risk of CVD, Clough et al were unable to show any improvements in microvascular function over the 6 months study [30].…”

“…The study be Clough et al [30] assessed muscle microvascular function in 38 consented volunteers with two or more features of metabolic syndrome (central obesity, dyslipidaemia, high blood pressure and dysglycaemia), before and after 6 months lipid lowering therapy (Atorvastatin 40mg o.d.) or placebo control.…”

Highlights of the 25th Conference of the European Society for Microcirculation

“…These data suggested attenuation in capacity for blood/tissue exchange in people with features of metabolic syndrome. Although statins are known to decrease risk of CVD, Clough et al were unable to show any improvements in microvascular function over the 6 months study [30].Finally, Bagi et al proposed the existence of several adaptive mechanisms that may maintain the dilatory function of coronary microvessels in obesity. Among others, increased production of hydrogen 640 peroxide [31], cyclooxygenase-2-derived dilator prostaglandins [32,33] as well as activation of soluble guanylate cyclase in vascular smooth muscle cells have been suggested to maintain or enhance the dilatory function of coronary microvessels [34,35].…”

“…By using OCT technique they were able to image the impaired vascular function of small arteries of different mouse strains in response to high-fat diet in vivo [29]. This imaging procedure offers the ability to display differences in early stages of atherosclerotic pathogenesis.The study be Clough et al [30] assessed muscle microvascular function in 38 consented volunteers with two or more features of metabolic syndrome (central obesity, dyslipidaemia, high blood pressure and dysglycaemia), before and after 6 months lipid lowering therapy (Atorvastatin 40mg o.d.) or placebo control.…”