Oral glucose challenge impairs skeletal muscle microvascular blood flow in healthy people

Abstract

Skeletal muscle microvascular (capillary) blood flow increases in the postprandial state or during insulin infusion due to dilation of precapillary arterioles to augment glucose disposal. This effect occurs independently of changes in large artery function. However, acute hyperglycemia impairs vascular function, causes insulin to vasoconstrict precapillary arterioles, and causes muscle insulin resistance in vivo. We hypothesized that acute hyperglycemia impairs postprandial muscle microvascular perfusion, without disrupting normal large artery hemodynamics, in healthy humans. Fifteen healthy people (5 F/10 M) underwent an oral glucose challenge (OGC, 50 g glucose) and a mixed-meal challenge (MMC) on two separate occasions (randomized, crossover design). At 1 h, both challenges produced a comparable increase (6-fold) in plasma insulin levels. However, the OGC produced a 1.5-fold higher increase in blood glucose compared with the MMC 1 h postingestion. Forearm muscle microvascular blood volume and flow (contrast-enhanced ultrasound) were increased during the MMC (1.3- and 1.9-fold from baseline, respectively, P < 0.05 for both) but decreased during the OGC (0.7- and 0.6-fold from baseline, respectively, P < 0.05 for both) despite a similar hyperinsulinemia. Both challenges stimulated brachial artery flow (ultrasound) and heart rate to a similar extent, as well as yielding comparable decreases in diastolic blood pressure and total vascular resistance. Systolic blood pressure and aortic stiffness remained unaltered by either challenge. Independently of large artery hemodynamics, hyperglycemia impairs muscle microvascular blood flow, potentially limiting glucose disposal into skeletal muscle. The OGC reduced microvascular blood flow in muscle peripherally and therefore may underestimate the importance of skeletal muscle in postprandial glucose disposal.

Postprandial microvascular blood flow in skeletal muscle: Similarities and disparities to the hyperinsulinaemic‐euglycaemic clamp

“…However, we have recently examined the effect of pure glucose ingestion and skeletal muscle microvascular function. The ingestion of a 50 g oral glucose challenge showed no increases in skeletal muscle microvascular blood flow of healthy subjects despite a rise in plasma insulin, suggesting microvascular impairment . In contrast, a liquid mixed meal matched for plasma insulin concentration, enhanced microvascular blood flow in the same participants .…”

“…Interestingly, there are inconsistencies observed in the microvascular responses to mixed meals as well as single macronutrients, with evidence to suggest that the fat and carbohydrate content of a meal could dictate this response . A small body of work has focussed specifically on the relationship between acute glycaemia and microvascular function, with evidence to suggest that elevation of plasma glucose above a critical point could be detrimental to microvascular action . Considerable gaps in our understanding of this relationship remain, with little known regarding other factors such as gut‐derived hormones (or other factors) that may be playing a role in microvascular regulation.…”

“…The ingestion of a 50 g oral glucose challenge showed no increases in skeletal muscle microvascular blood flow of healthy subjects despite a rise in plasma insulin, suggesting microvascular impairment. 105 In contrast, a liquid mixed meal matched for plasma insulin concentration, enhanced microvascular blood flow in the same participants. 105 These findings are also supported by Tobin and colleagues who demonstrated loss of microvascular blood flow in forearm skeletal muscle of healthy individuals following the ingestion of a 75 g glucose load.…”

“…This suggests that more work is required to understand the muscle microvascular blood flow responses to different amounts of macronutrients (particularly fat and carbohydrate) consumed alone and in mixed meals. Similarly, there is little known regarding the mechanisms behind blunted and impaired microvascular blood flow observed following the ingestion of high‐fat, high‐carbohydrate mixed meals and glucose alone …”

Six Weeks of Morning Fasting Causes Little Adaptation of Metabolic or Appetite Responses to Feeding in Adults with Obesity

“…Our current investigation using a mixed meal does not support these findings, as insulin concentrations were unaffected by either intervention. This discrepancy could be due to recently reported differences in muscle microvascular perfusion with oral glucose ingestion relative to a mixed meal , which highlight that fat and protein may have played a role in the discrepancy between the methods as well as the importance of utilizing mixed‐macronutrient meal challenges for generalizability. It should also be considered that other related measurements such as homeostatic model assessment‐insulin resistance, insulin sensitivity indices, and adipose tissue glucose uptake in response to insulin were found to be unaffected by either intervention .…”