Insulin Increases The Central-To-Peripheral Arterial Stiffness Gradient in Response To Hyperglycemia in Healthy Humans: A Randomized Four-Way Crossover Study
Abstract Background: Increasing arterial stiffness is a physiological feature of vascular aging that is accelerated by conditions that enhance cardiovascular risk, including diabetes mellitus. Emerging evidence demonstrates that reversal of the normal central-to-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.Methods: We tested the effect of acutely increasing plasma glucose, plasma insulin, or both on central arterial stiffness (carotid-femoral pulse wave velocity) and peripheral arterial stiffness (radial artery augmentation index) in a randomized, four-way, crossover study of 19 healthy young adults. We also measured myocardial oxygen supply-demand (subendocardial viability ratio) and hemodynamic function. Results: Carotid-femoral pulse wave velocity increased during hyperglycemic-hyperinsulinemia (+0.4 m/s; p=0.02) but not with euglycemia, hyperglycemia, or euglycemic-hyperinsulinemia. There were no significant changes in radial artery augmentation index within any protocol (all p>0.05), though this value trended lower with hyperglycemic-hyperinsulinemia (opposite of the observed effect on carotid-femoral pulse wave velocity). No changes were observed in subendocardial viability ratio within any protocol. Heart rate significantly increased only during hyperglycemic-hyperinsulinemia (+3.62 bpm; p=0.02). There was a significant inverse correlation between peripheral and arterial stiffness during hyperglycemic-hyperinsulinemia. Conclusions: We conclude that combined hyperglycemia and hyperinsulinemia acutely increases aortic stiffness, diminishes the normal central-to-peripheral arterial stiffness gradient, and increases heart rate in healthy humans. (ClinicalTrials.gov number NCT03520569; registered 9 May 2018).Clinical Trial Information: ClinicalTrials.gov identifier NCT03520569 (registered 9 May 2018).