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, 27 (4), 354-61

Contributions of Dysglycaemia, Obesity, and Insulin Resistance to Impaired Endothelium-Dependent Vasodilation in Humans


Contributions of Dysglycaemia, Obesity, and Insulin Resistance to Impaired Endothelium-Dependent Vasodilation in Humans

K A Han et al. Diabetes Metab Res Rev.


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.


Figure 1
Figure 1
Endothelium-dependent vasodilation (EDV) and insulin resistance by weight and glycemia categories. EDV is plotted on the Y axis as the square root transformed percent change of leg blood flow with application of methacholine chloride. Clusters represent unadjusted group means (left), and estimated means following adjustment for age, sex and race (right). For both analyses the group means were statistically different by ANOVA; groups sharing the same symbol within each cluster are not different from each other on posthoc pairwise analyses. DM2 = type 2 diabetes; Dys = dysglycemic; NGT = normal glucose tolerant; NO = non-obese; OB = obese.

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