J Clin Endocrinol Metab. 2022 Apr 16:dgac233. doi: 10.1210/clinem/dgac233. Online ahead of print.
ABSTRACT
PURPOSE: People characterized as late chronotype have elevated type 2 diabetes and cardiovascular disease risk compared to early chronotype. It is unclear how chronotype is associated with insulin sensitivity, metabolic flexibility, or plasma TCA cycle intermediates concentration, amino acids (AA), and/or beta-oxidation.
METHODS: The Morning-Eveningness Questionnaire (MEQ) was used to classify adults with metabolic syndrome (ATP III Criteria) as either early (n=15 (13F), MEQ = 64.7±1.4) or late (n=19 (16F), MEQ = 45.5±1.3) chronotype. Fasting bloods determined hepatic (HOMA-IR) and adipose insulin resistance (Adipose-IR) while a 120 min euglycemic clamp (40 mU/m 2/min, 5 mmoL/L) was performed to test peripheral insulin sensitivity (glucose infusion rate (GIR)). Carbohydrate (CHOOX) and fat oxidation (FOX) as well as non-oxidative glucose disposal (NOGD) were also estimated (indirect calorimetry). Plasma TCA intermediates, AA, and acyl-carnitines were measured along with VO2max and body composition (DXA).
RESULTS: There were no statistical differences in age, BMI, fat-free mass, VO2max or ATP III criteria between groups. Early chronotype, however, had higher peripheral insulin sensitivity (P=0.009) and lower HOMA-IR (P=0.02) and Adipose-IR (P=0.05) compared to late chronotype. Further, early chronotype had higher NOGD (P=0.008) and greater insulin-stimulated CHOOX (P=0.02). While fasting lactate (P=0.01), TCA intermediates (isocitrate, ꭤ-ketoglutarate, succinate, fumarate, malate (all P≤0.04)) and some AA (proline, isoleucine (P=0.003-0.05)) were lower in early chronotype, other AA (threonine, histidine, arginine (all P≤0.05)) and most acyl-carnitines were higher (P≤0.05) compared to late chronotype.
CONCLUSIONS: Greater insulin sensitivity and metabolic flexibility relates to plasma TCA concentration in early chronotype.
PMID:35429387 | DOI:10.1210/clinem/dgac233
