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

Introduction: Increasing arterial stiffness is a feature of vascular aging that is accelerated by conditions that enhance cardiovascular risk, including diabetes mellitus. Multiple studies demonstrate divergence of carotid-femoral pulse wave velocity and augmentation index in persons with diabetes mellitus, though mechanisms responsible for this are unclear. Materials and Methods: We tested the effect of acutely and independently increasing plasma glucose, plasma insulin, or both on hemodynamic function and markers of arterial stiffness (including carotid-femoral pulse wave velocity, augmentation index, forward and backward wave reflection amplitude, and wave reflection magnitude) in a four-arm, randomized study of healthy young adults. Results: Carotid-femoral pulse wave velocity increased only during hyperglycemic-hyperinsulinemia (+0.36 m/s; p=0.032), while other markers of arterial stiffness did not change (all p>0.05). Heart rate (+3.62 bpm; p=0.009), mean arterial pressure (+4.14 mmHg; p=0.033), central diastolic blood pressure (+4.16 mmHg; p=0.038), and peripheral diastolic blood pressure (+4.09 mmHg; p=0.044) also significantly increased during hyperglycemic-hyperinsulinemia. Conclusions: We conclude that the acute combination of moderate hyperglycemia and hyperinsulinemia preferentially stiffens central elastic arteries. This effect may be due to increased sympathetic activity. (ClinicalTrials.gov number NCT03520569; registered 9 May 2018).