title: Postprandial microvascular function deteriorates in parallel with gradual worsening of insulin sensitivity and glucose tolerance in men with the metabolic syndrome or type 2 diabetes.
abstract: OBJECTIVE
  Hyperinsulinaemia-induced whole-body glucose uptake during a euglycaemic-hyperinsulinaemic clamp is partly mediated by increased capillary density. We hypothesised that physiological insulinaemia in response to a mixed meal may also enhance microvascular function, and that this may be impaired in insulin-resistant individuals and patients with type 2 diabetes.
  
  
  METHODS
  Twelve men with uncomplicated type 2 diabetes, 13 with metabolic syndrome and 12 age-matched healthy normoglycaemic controls, mean age 57 ± 6 years, underwent skin capillary video microscopy before and 60 and 120 min following a standardised mixed meal to measure baseline capillary density (BCD) and capillary density during post-occlusive peak reactive hyperaemia (PRH), also termed capillary recruitment. Oral glucose insulin sensitivity (Matsuda index) and postprandial hyperglycaemia (2 h AUC(glucose)) were calculated.
  
  
  RESULTS
  Fasting BCD was similar among groups, but fasting PRH was lowest in diabetes (p < 0.05). Postprandially, both BCD and PRH increased in all groups (p < 0.001); however, the meal-related increase in BCD was significantly lower in diabetes and metabolic syndrome vs controls (both p < 0.05). At all time points, postprandial PRH was lower in both diabetes and metabolic syndrome vs controls (both p < 0.05). In pooled analysis, postprandial mean PRH correlated with Matsuda index (r = 0.386, p = 0.018) and inversely with 2 h AUC(glucose) (r = -0.336, p = 0.042).
  
  
  CONCLUSIONS
  Gradual deterioration in meal-related capillary recruitment was paralleled by decreasing insulin sensitivity and postprandial hyperglycaemia, as assessed in healthy normoglycaemic men, men with the metabolic syndrome and those with type 2 diabetes. These findings suggest that in both impaired glucose tolerance and in overt diabetes microvascular dysfunction might contribute to postprandial dysglycaemia.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00721552.
authors.affiliation: Diabetes Center, Department of Internal Medicine, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands. r.vangenugten@vumc.nl
authors.forename: R E
authors.initials: RE
authors.lastname: van Genugten
authors.forename: E H
authors.initials: EH
authors.lastname: Serné
authors.forename: M W
authors.initials: MW
authors.lastname: Heymans
authors.forename: D H
authors.initials: DH
authors.lastname: van Raalte
authors.forename: M
authors.initials: M
authors.lastname: Diamant
mesh_terms: D000818:Animals; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D018149:Glucose Intolerance / Q000503:physiopathology*; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D024821:Metabolic Syndrome / Q000503:physiopathology*; D008875:Middle Aged; D019518:Postprandial Period