title: 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 (Kf) and that 6 months of high-dose statin therapy would improve microvascular function in people with central obesity.
  
  
  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.
authors.affiliation: School of Medicine, University of Southampton, Southampton, UK.
authors.forename: Geraldine F
authors.initials: GF
authors.lastname: Clough
authors.forename: Magdalena
authors.initials: M
authors.lastname: Turzyniecka
authors.forename: Lara
authors.initials: L
authors.lastname: Walter
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Krentz
authors.forename: Sarah H
authors.initials: SH
authors.lastname: Wild
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Chipperfield
authors.forename: John
authors.initials: J
authors.lastname: Gamble
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Byrne
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000069059:Atorvastatin; D001692:Biological Transport / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004311:Double-Blind Method; D004734:Energy Metabolism / Q000187:drug effects; D005080:Exercise Test; D005260:Female; D005947:Glucose / Q000378:metabolism; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007328:Insulin / Q000494:pharmacology*; D008055:Lipids / Q000097:blood; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology*; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000503:physiopathology*; D009765:Obesity / Q000097:blood / Q000503:physiopathology*; D011758:Pyrroles / Q000627:therapeutic use*
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007328:Insulin; D008055:Lipids; D011758:Pyrroles; D000069059:Atorvastatin; D005947:Glucose