title: Contributions of dysglycaemia, obesity, and insulin resistance to impaired endothelium-dependent vasodilation in humans.
abstract: BACKGROUND
  Individual effects of hyperglycaemia and obesity to impair vascular health are recognized. However, the relative contributions of dysglycaemia versus other obesity-related traits to vascular dysfunction have not been systematically evaluated.
  
  
  METHODS
  We undertook a cross-sectional evaluation of factors contributing to vascular function in 271 consecutive subjects, categorized as non-obese normal glucose tolerant (n = 115), non-obese dysglycaemic (n = 32), obese normal glucose tolerant (n = 57), obese dysglycaemic (n = 38), or type 2 diabetic (n = 29). Vascular function was measured invasively as leg blood flow responses to methacholine chloride, an endothelium-dependent vasodilator. Categorical and continuous analyses were carried out to assess the contributions of hyperglycaemia to vascular dysfunction.
  
  
  RESULTS
  Even among normoglycaemic subjects, obese subjects had impaired vascular function compared to non-obese subjects (p = 0.004). Vascular function was also impaired in non-obese dysglycaemic subjects (p = 0.04 versus non-obese normoglycaemic subjects), to a level comparable to normoglycaemic obese subjects. Within obese subject groups, gradations of dysglycaemia including the presence of diabetes were not associated with further worsening of these vascular responses beyond the effect of obesity alone (p = not significant comparing all obese groups, p < 0.001 versus lean normoglycaemic subjects). After univariate and multivariable modelling analyses we found that effects of glycaemia were less powerful than effects of insulin resistance and obesity on vascular dysfunction.
  
  
  CONCLUSIONS
  Dysglycaemia contributes to impaired vascular function in non-obese subjects, but obesity and insulin resistance are more important determinants of vascular function in obese and diabetic subjects.
authors.affiliation: Division of Endocrinology & Metabolism, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Han
authors.forename: Y
authors.initials: Y
authors.lastname: Patel
authors.forename: A A
authors.initials: AA
authors.lastname: Lteif
authors.forename: R
authors.initials: R
authors.lastname: Chisholm
authors.forename: Kieren J
authors.initials: KJ
authors.lastname: Mather
mesh_terms: D000328:Adult; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000150:complications / Q000503:physiopathology*; D007333:Insulin Resistance; D007866:Leg / Q000098:blood supply; D008297:Male; D016210:Methacholine Chloride; D009765:Obesity / Q000150:complications / Q000503:physiopathology*; D011236:Prediabetic State / Q000150:complications / Q000503:physiopathology; D012039:Regional Blood Flow / Q000187:drug effects; D012720:Severity of Illness Index; D013223:Statistics as Topic; D014652:Vascular Diseases / Q000175:diagnosis / Q000209:etiology*; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents
chemical_list: D014665:Vasodilator Agents; D016210:Methacholine Chloride