Meal-Related Increases in Microvascular Vasomotion Are Impaired in Obese Individuals

Abstract

Background and aims: Steady state hyperinsulinaemia during a hyperinsulinaemic euglycaemic clamp stimulates endothelium-dependent vasomotion as well as capillary recruitment, which contribute to increased glucose uptake; these phenomena have been shown to be blunted in obesity. If insulin's effects on microcirculatory function indeed play a physiological role in regulating insulin-mediated glucose uptake, such effects should be demonstrable not only during steady-state hyperinsulinaemia, but also after meal ingestion. The aim of the present study was to investigate the effects of an oral glucose load and a liquid mixed meal on cutaneous microvascular vasomotion in lean and obese subjects. Materials and methods: A randomised, placebo-controlled trial was performed in 18 lean (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 (tap water) on microvascular function. Skin blood flow was measured by laser Doppler flowmetry (LDF). Vasomotion was examined by Fourier analysis of the LDF signal. Results: Both the glucose drink and the liquid mixed meal, but not the water drink, induced hyperinsulinaemia. The levels of hyperinsulinaemia were higher in obese compared to healthy subjects (glucose drink: 98.1±82.5 vs. 39.2±17.0 mU/l, P<0.05; mixed meal: 99.8±78.9 vs. 52.7±20.5 mU/l P=0.07). Water intake did not alter the energy density of any of the five frequency components in either the lean and obese group. Intake of the glucose drink increased the endothelial component of vasomotion (P<0.05) in lean subjects. In lean subjects, intake of the mixed meal drink increased the energy density of all five frequency components (P<0.01, P<0.01, P<0.01, P<0.01, and P<0.05, respectively), and the total energy density of the entire spectrum (P<0.01). In obese individuals, neither the glucose nor the mixed meal drink had any effect on the energy density of the five frequency bands or the total energy density. The increase in the energy density of the endothelial, neurogenic, and respiratory frequency components and the total energy density in lean individuals in response to the mixed meal drink was significantly different from the response to the mixed meal drink in obese individuals (P<0.01, P<0.05, P<0.05, and P<0.01, respectively). Conclusion: Our data demonstrate that ingestion of a meal increases microvascular vasomotion in lean individuals. In addition, we found that the increase in microvascular vasomotion with meal ingestion was impaired in obese individuals and that this lack of meal-induced stimulation of microvascular vasomotion paralleled blunted insulin-stimulated glucose disposal after meal feeding in these subjects. Thus, these data are consistent with a physiological role for insulin-stimulated microvascular vasomotion in insulin- mediated glucose uptake in the postprandial state.