title: Metformin improves skin capillary reactivity in normoglycaemic subjects with the metabolic syndrome.
abstract: OBJECTIVE
  Insulin resistance and a parental history of diabetes mellitus are independently associated with endothelial dysfunction. Oxidative stress has a pivotal role in the pathophysiology of vascular injury. Metformin, in addition to its glucose-lowering properties, has vasculoprotective effects. We investigated whether metformin has beneficial effects on the nutritive skin capillary circulation and deceases oxidative stress in a group at high risk for Type 2 diabetes mellitus (T2DM) and cardiovascular disease.
  
  
  METHODS
  Thirty normoglycaemic subjects with the metabolic syndrome (MS),who had first-degree relatives with T2DM, participated. The mean age was 39.1 +/- 8.4 years and body mass index (BMI) 35.7 +/- 4.8 kg/m2 (mean +/- SD).
  
  
  METHODS
  were randomized 1 : 1 to receive placebo (n=14) or metformin (n=16; 1700 mg/day) in a double-blind study. At baseline and post treatment, blood and urine samples were collected for biochemical and 8-epi-prostaglandin F2alpha (8-epi-PGF2alpha) analysis, respectively. Microcirculation was assessed by nailfold videocapillaroscopy, analysing afferent (AF), efferent (EF) and apical (AP) diameters of capillary loops, functional capillary density (FCD), red blood cell velocity at rest (RBCV), after 1 min arterial occlusion (RBCVmax) and time (TRBCVmax)taken to reach it.
  
  
  RESULTS
  Groups did not differ significantly in anthropometric, clinical, laboratory or microvascular measurements at baseline. In the metformin group, weight,BMI, systolic blood pressure and fasting plasma glucose fell, and lipid profile and microcirculatory parameters FCD, AF, EF, AP, RBCVmaxand TRBCVmax improved (all P<0.01). No relationship between clinico-laboratory parameters and microvascular reactivity was observed, except for changes in total and low density lipoprotein-cholesterol and RBCVmax* 8-epi-PGF2alpha did not change significantly in either group.
  
  
  CONCLUSIONS
  Metformin improved skin capillary reactivity in normoglycaemic MS subjects independently of significant changes in 8-epi-PGF2alpha levels.
authors.affiliation: Department of Physiological Sciences, Laboratóriode Pesquisas em Microcirculação, State University of Rio de Janeiro, Rio de Janeiro, Brazil. gkraemer@ig.com.br
authors.forename: L G
authors.initials: LG
authors.lastname: Kraemer de Aguiar
authors.forename: C M
authors.initials: CM
authors.lastname: Laflor
authors.forename: L
authors.initials: L
authors.lastname: Bahia
authors.forename: N R
authors.initials: NR
authors.lastname: Villela
authors.forename: N
authors.initials: N
authors.lastname: Wiernsperger
authors.forename: D A
authors.initials: DA
authors.lastname: Bottino
authors.forename: E
authors.initials: E
authors.lastname: Bouskela
mesh_terms: D000328:Adult; D002196:Capillaries; D003327:Coronary Disease / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications*; D008687:Metformin / Q000627:therapeutic use*; D008833:Microcirculation / Q000502:physiology; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology; D012307:Risk Factors; D012867:Skin / Q000098:blood supply
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin