Altered Aortic Waveform Responses To Insulin In Late Chronotype With Metabolic Syndrome

Abstract

PURPOSE: Late chronotype (LC) is linked to insulin resistance & cardiovascular disease. However, it is unclear if insulin reduces aortic waveforms & inflammation in LC versus early chronotype (EC). METHODS: Using the Morning-Eveningness Questionnaire (MEQ), adults with metabolic syndrome (MetS; 54.9 ± 1.1y; VO2MAX 22.2 ± 0.7 ml/kg/min, 3.5 ± 0.1 ATP-III score) were classified as either LC (n = 19 (16F); MEQ = 45.5 ± 1.3) or EC (n = 20 (16F); MEQ = 63.5 ± 1.2). A 120 min euglycemic clamp (40 mU/m2/min, 90 mg/dl) with indirect calorimetry was used to determine metabolic insulin sensitivity (glucose infusion rate (GIR)) & non-oxidized glucose disposal (NOGD; GIR-total carbohydrate oxidation). Aortic waveforms via applanation tonometry were taken at 0 & 120-min of the clamp & included augmentation index (AIx75), augmentation pressure (AP), pulse pressure amplification (PPA), mean arterial pressure (MAP), as well as forward (Pf) & backward (Pb) pulse wave. Inflammation (ICAM, VCAM, hs-CRP, TNF-α, & MMP-7) was also assessed before and after the clamp. RESULTS: While age, fat mass, & ATP III score were similar between groups, LC had higher FFM (P = 0.04) and lower VO2MAX (P = 0.05), GIR (P < 0.01) and NOGD (P < 0.01) than EC. No difference in 0 min waveforms were noted. Nonetheless, LC had increases in Pf versus EC (∆:1.9 ± 1.1 vs. -2.3 ± 1.0 mmHg; P = 0.007) during insulin infusion, though reflection magnitude decreased similarly (∆: -6.0 ± 2.2 vs. -5.9 ± 2.3%; P = 0.02). Further, both LC and EC had elevated PPA (∆: 0.04 ± 0.02 vs. 0.05 ± 0.02 mmHg; P = 0.02) & reduced AP (∆: -2.0 ± 1.0 vs. -2.8 ± 1.1 mmHg; P = 0.02) in response to insulin, while only EC had lower AIx75 (P = 0.02). LC had increased TNF-α (P = 0.04) and decreased MMP-7 (P = 0.04) in response to insulin, and EC decreased in hs-CRP (P = 0.009), ICAM (P = 0.009), and VCAM (P = 0.09). VO2MAX correlated with insulin-mediated reductions in AIx75 (r = -0.56, P < 0.01) and AP (r = -0.49, P < 0.01), while NOGD related to decreased AP during insulin (r = -0.44, P = 0.03) and Pf (r = -0.43, P = 0.04). Insulin-mediated reductions in VCAM also correlated with lower MAP during the clamp (r = 0.41, P = 0.03). CONCLUSIONS: LC was depicted by altered aortic waveform and inflammatory responses to insulin in MetS. More work is needed to assess peripheral endothelial function in chronotype. Funding: NIH RO1-HL130296