Abstract
Vascular insulin resistance is a feature of obesity and type 2 diabetes that contributes to the genesis of vascular disease and glycemic dysregulation. Data from preclinical models indicate that vascular insulin resistance is an early event in the disease course, preceding the development of insulin resistance in metabolically active tissues. Whether this is translatable to humans requires further investigation. To this end, we examined if vascular insulin resistance develops when young healthy individuals (n = 18 men, n = 18 women) transition to an obesogenic lifestyle that would ultimately cause whole-body insulin resistance. Specifically, we hypothesized that short-term (10 days) exposure to reduced ambulatory activity (from >10 000 to <5000 steps/day) and increased consumption of sugar-sweetened beverages (6 cans/day) would be sufficient to prompt vascular insulin resistance. Furthermore, given that incidence of insulin resistance and cardiovascular disease is lower in premenopausal women than in men, we postulated that young females would be protected against vascular insulin resistance. Consistent with this hypothesis, we report that after reduced ambulation and increased ingestion of carbonated beverages high in sugar, young healthy men, but not women, exhibited a blunted leg blood flow response to insulin and suppressed skeletal muscle microvascular perfusion. These findings were associated with a decrease in plasma adropin and nitrite concentrations. This is the first evidence in humans that vascular insulin resistance can be provoked by short-term adverse lifestyle changes. It is also the first documentation of a sexual dimorphism in the development of vascular insulin resistance in association with changes in adropin levels.