Abstract
Objective: Steady state hyperinsulinaemia during a hyperinsulinaemic euglycaemic clamp stimulates endothelium-dependent vasomotion and vasodilation as well as capillary recruitment, which contribute to increased glucose uptake; these phenomena have been shown to be blunted in obesity. The aim of the present study was to investigate whether similar results can be obtained during dynamic hyperinsulinaemia as induced by a glucose load or a mixed meal. Design and Methods: A randomised, placebo-controlled trial was performed in 18 healthy (BMI 22.5 ± 1.7 kg/m2) and 13 obese (BMI 34.0 ± 3.5 kg/m2) subjects, to examine the effects of a glucose drink (75 g glucose), a 495-kcal liquid mixed meal (60% carbohydrates, 25% proteins, 15% fat) or placebo (a similar amount of tap water) on microvascular function. Skin endothelium-(in)dependent vasodilatation was evaluated by laser Doppler flowmetry (LDF) with iontophoresis of acetylcholine (Ach) and sodium nitroprusside (SNP). Vasomotion was examined by Fourier analysis of the LDF signal. Results: Both the glucose drink and the liquid mixed meal, but not placebo, induced hyperinsulinaemia. The levels of hyperinsulinaemia were higher in obese compared to healthy subjects (peak levels glucose drink: 95.9 vs. 54.2 mU/l, P < 0.05; mixed meal: 107.6 vs. 59.7 mU/l P < 0.05). Compared to placebo, vasomotion analysis showed increased endothelial activity in healthy subjects following the glucose drink (delta energy density (median (interquartile range) +0.11 (−0.04 – +0.25); P < 0.05) and meal drink (+0.16 (0.05 – 0.29); P = 0.001). Compared to healthy subjects, a significant decrease of endothelial activity was found in obese subjects following the meal drink (−0.09 (−0.23–0.13) vs 0.16 (0.05 – 0.29); P < 0.05). No changes in endothelium-(in)dependent vasodilatation following iontophoresis of Ach or SNP were found in either group. Conclusion: A glucose load and a mixed meal, which are accompanied by non-steady state hyperinsulinaemia, increase endothelial vasomotion in healthy individuals. These responses are blunted in obese subjects. These data suggest impairment of microvascular function in the postprandial state in obese individuals.
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