315-OR: Hyperglycemia Increases Central Aortic Stiffness in Response to Insulin in Healthy Humans

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.

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Insulin Increases Central Aortic Stiffness in Response To Hyperglycemia in Healthy Humans: A Randomized Four-Way Crossover Study

10.21203/rs.3.rs-72339/v2 ◽

2020 ◽

Author(s):

William B Horton ◽

Linda A Jahn ◽

Lee M Hartline ◽

Kevin W Aylor ◽

Eugene J Barrett

Keyword(s):

Heart Rate ◽

Arterial Stiffness ◽

Pulse Wave Velocity ◽

Crossover Study ◽

Wave Velocity ◽

Aortic Stiffness ◽

Pulse Wave ◽

Augmentation Index ◽

Healthy Humans ◽

Peripheral Arterial

Abstract Increasing arterial stiffness is a feature of vascular aging that is accelerated by conditions that enhance cardiovascular risk, including diabetes mellitus. Emerging evidence demonstrates that reversal of the normal lower central to higher peripheral arterial stiffness gradient predicts adverse cardiovascular consequences, including target organ damage. Preferential stiffening of central over peripheral arteries has been reported in type 2 diabetes, though mechanisms for this remain unclear. We tested the effect of acutely increasing plasma glucose, plasma insulin, or both on hemodynamic function, central aortic stiffness (carotid-femoral pulse wave velocity), and peripheral arterial stiffness (augmentation index) in a randomized, four-way, crossover study of 19 healthy young adults. Carotid-femoral pulse wave velocity increased only during hyperglycemic-hyperinsulinemia (+0.4 m/s; p=0.02), while augmentation index did not change significantly within any intervention (all p>0.05). Heart rate significantly increased only during hyperglycemic-hyperinsulinemia (+3.62 bpm; p=0.02). There was a significant inverse correlation between the changes of central and peripheral arterial stiffness only during hyperglycemic-hyperinsulinemia. We conclude that combined hyperglycemia and hyperinsulinemia acutely increased aortic stiffness, changed the normal central-to-peripheral arterial stiffness gradient, and increased heart rate in healthy humans. (ClinicalTrials.gov number NCT03520569; registered 9 May 2018).

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