Morning Versus Intermediate Chronotype Has Higher Vascular Insulin Sensitivity In Adults With Obesity

PURPOSE: Endothelial dysfunction is a risk factor for cardiovascular disease (CVD). Chronotype reflects a circadian rhythmicity that regulates endothelial function throughout the day. While morning chronotype (MC) usually has low CVD risk, no study has examined insulin action on endothelial function between chronotypes. We hypothesized MC would have higher vascular insulin sensitivity than intermediate chronotype (IC). METHODS: Adults with obesity were classified per Morningness-Eveningness Questionnaire (MEQ) as either MC (n = 27, 22F, MEQ = 63.7 ± 0.9, 53.8 ± 1.3y, 35.3 ± 0.9 kg/m2, 24.2 ± 0.8 ml/kg/min) or IC (n = 29, 23F, MEQ = 48.8 ± 1.5, 56.6 ± 1.7y, 35.7 ± 1.1 kg/m2, 22.5 ± 0.7 ml/kg/min). A 120 min euglycemic-hyperinsulinemic clamp (40 mU/m2/min, 90 mg/dL) was conducted in the morning to assess macrovascular insulin sensitivity via brachial artery flow-mediated dilation (%FMD, conduit artery), post-ischemic flow velocity (PIFV, resistance arteriole), as well as microvascular insulin sensitivity via contrast-enhanced ultrasound. Blood flow, vascular conductance, and shear stress, as well as microvascular flow velocity (MFV, filling rate), blood volume (MBV, perfusion) and blood flow (MBF) were calculated at 0 and 120 min of the clamp. Fasting plasma arginine and citrulline, as well as fasting and clamp-derived plasma nitrate/nitrite and ET-1, were assessed as surrogates of nitric oxide and constriction. Aerobic fitness (VO2max) and body composition (DXA) were also collected. RESULTS: MC had higher VO2max compared to IC (P < 0.01), though no difference in BMI or fat mass. While fasting FMD was similar between groups, insulin reduced FMD corrected to shear stress and MBV in IC, compared to rises in MC, independent of VO2max (interaction effect, both P ≤ 0.02). Conversely, insulin increased blood flow, vascular conductance, and heart rate similarly between groups (time effect, all P ≤ 0.02). IC had lower fasting nitrate (P = 0.03) and arginine (P = 0.07). Higher MEQ correlated with higher FMD (r = 0.33, P = 0.03) and lower PIFV (r = -0.33, P = 0.03) as well as shear rate (r = -0.36, P = 0.02) at 120 min. CONCLUSIONS: MC had higher vascular insulin sensitivity versus IC, independent of fitness. Further work is needed to clarify chronotype influences on endothelial function and assess if chrono-exercise can reduce CVD risk.