Hyperglycemia does not inhibit insulin’s effects on microvascular perfusion in healthy humans: a randomized crossover study

Abstract

Diabetes mellitus accelerates vascular disease through multiple biochemical pathways driven by hyperglycemia, with insulin resistance and/or hyperinsulinemia also contributing. Persons with diabetes mellitus experience premature large vessel and microvascular disease when compared with normoglycemic controls. Currently, there is a paucity of clinical data identifying how acutely the vasculature responds to hyperglycemia and whether other physiological factors (e.g., vasoactive hormones) contribute. To our knowledge, no prior studies have examined the dynamic effects of acute hyperglycemia on insulin-mediated actions on both micro- and macrovascular function in the same subjects. In this randomized crossover trial, healthy young adults underwent two infusion protocols designed to compare the effects of insulin infusion during euglycemia and hyperglycemia on micro- and macrovascular function. Both euglycemic- and hyperglycemic-hyperinsulinemia increased skeletal (but not cardiac) muscle microvascular blood volume (each P < 0.02) and blood flow (each P < 0.04) significantly, and these increases did not differ between protocols. Hyperglycemic-hyperinsulinemia trended toward increased carotid-femoral pulse wave velocity (indicating increased aortic stiffness; P = 0.065 after Bonferroni adjustment), whereas euglycemic-hyperinsulinemia did not. There were no changes in postischemic flow velocity or brachial artery flow-mediated dilation during either protocol. Plasma endothelin-1 levels significantly decreased during both protocols (each P < 0.02). In this study, acute hyperglycemia for 4 h did not inhibit insulin’s ability to increase skeletal muscle microvascular perfusion but did provoke a slight increase in aortic stiffness. Hyperglycemia also did not adversely affect myocardial microvascular perfusion or endothelial function or prevent the decline of endothelin-1 during insulin infusion.