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.

This is the second in the series of historical articles dealing with developments in clinical pathology. As one of the most commonly measured analytes in pathology, the assessment of glucose dates back to the time of the ancient Egyptians. It was only in the 19th century that advances in chemistry led to the identification of the sugar in urine being glucose. The following century witnessed the development of more chemical and enzymatic methods which became incorporated into the modern analysers and point-of-care instruments which are as ubiquitous as the modern day cellphones. Tracking the milestones in these developments shows the striking paradigms and the many parallels in the development of other clinical chemistry methods.

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.

Cardiorespiratory fitness [maximal O2 consumption (VO2max)] is an independent risk factor for type 2 diabetes; but in individuals at risk, factors influencing VO2max are poorly understood. We tested the hypothesis that VO2max is associated with diastolic function [subendocardial variability ratio (SEVR), %], as diastolic function influences myocardial perfusion. We studied 47 men and women with central obesity without diabetes. We measured fitness (VO2max) by treadmill testing and diastolic function (SEVR%) by pulse-wave analysis. We measured other factors influencing this relationship: insulin sensitivity [whole body glucose uptake-to-insulin concentration ratio (M/I)] by hyperinsulinemic euglycemic clamp, fatness by MR imaging and dual-energy X-ray absorptiometry, physical activity energy expenditure (metabolic equivalents of tasks) by the Sensewear Pro2 device, and muscle microvascular exchange capacity (capillary filtration coefficient) by venous plethysmography. Mean age of the subjects was 51+/-9 (SD) yr. VO2max was associated with SEVR% (r=0.50, P=0.001), fatness (r=-0.39, P=0.008), and HbA1c (r=-0.35, P=0.018), but not with whole body glucose uptake-to-insulin concentration ratio, metabolic equivalents of tasks, or capillary filtration coefficient. In regression modeling with age, sex, fatness, and SEVR% as explanatory variables, only age, sex, and SEVR% were independently associated with VO2max (SEVR%--standardized B coefficient=0.37, 95% confidence interval=0.003-0.18, P=0.007). This model identified 46% of the variance in VO2max (R2=0.46, P=0.0001). There was a strong, independent association between VO2max and a measure of diastolic function in sedentary individuals with central obesity.