Microvascular Dysfunction and Hyperglycemia: A Vicious Cycle With Widespread Consequences

Abstract

Microvascular and metabolic physiology are tightly linked. This Perspective reviews evidence that 1) the relationship between hyperglycemia and microvascular dysfunction (MVD) is bidirectional and constitutes a vicious cycle; 2) MVD in diabetes affects many, if not all, organs, which may play a role in diabetes-associated comorbidities such as depression and cognitive impairment; and 3) MVD precedes, and contributes to, hyperglycemia in type 2 diabetes (T2D) through impairment of insulin-mediated glucose disposal and, possibly, insulin secretion. Obesity and adverse early-life exposures are important drivers of MVD. MVD can be improved through weight loss (in obesity) and through exercise. Pharmacological interventions to improve MVD are an active area of investigation.