Empagliflozin improves vascular insulin sensitivity and muscle perfusion in persons with type 2 diabetes.

Sodium glucose cotransporter 2 inhibitors (SGLT2is) improved major adverse cardiovascular events (MACE), heart failure, and renal outcomes in large trials; however, a thorough understanding of the vascular physiological changes contributing to these responses is lacking. We hypothesized that SGLT2i therapy would diminish vascular insulin resistance and improve hemodynamic function, which could improve clinical outcomes. To test this, we treated 11 persons with type 2 diabetes for 12 wk with 10 mg/day empagliflozin and measured vascular stiffness, endothelial function, peripheral and central arterial pressures, skeletal and cardiac muscle perfusion, and vascular biomarkers before and at 120 min of a euglycemic hyperinsulinemic clamp at and .

Impact of Free Fatty Acids on Vascular Insulin Responses Across the Arterial Tree: A Randomized Crossover Study.

Context: Vascular insulin resistance is commonly observed in obesity and diabetes; yet, insulin action across the vascular tree and the relationship between insulin responses at different vascular locations remains incompletely defined.

Objective: To elucidate the impact of elevated free fatty acids (FFAs) on insulin action across the arterial tree and define the relationship among insulin actions in the different arterial segments.

Methods: This randomized crossover study assigned healthy lean adults to 2 separate admissions with euglycemic insulin clamp superimposed for the final 120 minutes of 5-hour lipid or matched-volume saline infusion.

Insulin-induced vasoconstriction is prevalent in muscle microvasculature of otherwise healthy persons with type 1 diabetes.

Insulin's microvascular actions and their relationship to insulin's metabolic actions have not been well studied in adults with type 1 diabetes mellitus (T1DM). We compared the metabolic and selected micro- and macrovascular responses to insulin by healthy adult control ( = 16) and subjects with T1DM ( = 15) without clinical microvascular disease. We measured insulin's effect on ) skeletal muscle microvascular perfusion using contrast-enhanced ultrasound (CEU), ) arterial stiffness using carotid-femoral pulse-wave velocity (cfPWV) and radial artery pulse wave analysis (PWA), and ) metabolic insulin sensitivity by the glucose infusion rate (GIR) during a 2-h, 1 mU/min/kg euglycemic-insulin clamp.

Predictors of arterial stiffness in adolescents and adults with type 1 diabetes: a cross-sectional study.

Introduction: Individuals with type 1 diabetes have increased arterial stiffness compared with age-matched healthy controls. Our aim was to determine which hemodynamic and demographic factors predict arterial stiffness in this population.

Research Design And Methods: Carotid-femoral pulse wave velocity (cfPWV) was examined in 41 young adults and adolescents with type 1 diabetes without microvascular complications.

Nitric oxide-dependent micro- and macrovascular dysfunction occurs early in adolescents with type 1 diabetes.

Arterial stiffness and endothelial dysfunction are both reported in children with type 1 diabetes (DM1) and may predict future cardiovascular events. In health, nitric oxide (NO) relaxes arteries and increases microvascular perfusion. The relationships between NO-dependent macro- and microvascular functional responses and arterial stiffness have not been studied in adolescents with DM1.

Insulin-mediated muscle microvascular perfusion and its phenotypic predictors in humans.

Insulin increases muscle microvascular perfusion and enhances tissue insulin and nutrient delivery. Our aim was to determine phenotypic traits that foretell human muscle microvascular insulin responses. Hyperinsulinemic euglycemic clamps were performed in 97 adult humans who were lean and healthy, had class 1 obesity without comorbidities, or controlled type 1 diabetes without complications.

Insulin increases central aortic stiffness in response to hyperglycemia in healthy humans: A randomized four-arm 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.

Acute hyperglycaemia enhances both vascular endothelial function and cardiac and skeletal muscle microvascular function in healthy humans.

Key Points: Multiple clinical studies report that acute hyperglycaemia (induced by mixed meal or oral glucose) decreases arterial vascular function in healthy humans. Feeding, however, impacts autonomic output, blood pressure, and insulin and incretin secretion, which may themselves alter vascular function. No prior studies have examined the effect of acute hyperglycaemia on both macro- and microvascular function while controlling plasma insulin concentrations.

Hyperglycemia does not Inhibit Insulin's Effects on Microvascular Perfusion in Healthy Humans: A Randomized Crossover Study.

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 to normoglycemic controls. Currently there is a paucity of clinical data identifying how acutely the vasculature responds to hyperglycemia and whether other physiologic factors (e.