胰岛素敏感性和代谢灵活性与代谢综合征早型个体的血浆 TCA 水平平行。
Insulin Sensitivity and Metabolic Flexibility Parallel Plasma TCA Levels in Early Chronotype With Metabolic Syndrome.
机构信息
Rutgers University, New Brunswick, NJ, USA.
University of Virginia, Charlottesville, VA, USA.
出版信息
J Clin Endocrinol Metab. 2022 Jul 14;107(8):e3487-e3496. doi: 10.1210/clinem/dgac233.
CONTEXT
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.
OBJECTIVE
This study examined these metabolic associations with chronotype.
METHODS
The Morningness-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-minute euglycemic clamp (40 mU/m2/min, 5 mmoL/L) was performed to test peripheral insulin sensitivity (glucose infusion rate). Carbohydrate (CHOOX) and fat oxidation (FOX), as well as nonoxidative glucose disposal (NOGD), were also estimated (indirect calorimetry). Plasma tricarboxylic acid cycle (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 with 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, α-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 with late chronotype.
CONCLUSION
Greater insulin sensitivity and metabolic flexibility relates to plasma TCA concentration in early chronotype.
背景
与早型相比，晚型的 2 型糖尿病和心血管疾病风险更高。目前尚不清楚昼夜节律如何与胰岛素敏感性、代谢灵活性或血浆三羧酸 (TCA) 循环中间产物浓度、氨基酸 (AA) 和/或β-氧化相关。
目的
本研究旨在探讨这些代谢与昼夜节律的关系。
方法
使用 Morningness-Eveningness Questionnaire (MEQ) 将代谢综合征（ATP III 标准）患者分为早型（n=15[13F]，MEQ=64.7±1.4）和晚型（n=19[16F]，MEQ=45.5±1.3）。空腹血液检测肝（HOMA-IR）和脂肪胰岛素抵抗（Adipose-IR），同时进行 120 分钟的正常血糖钳夹（40 mU/m2/min，5 mmoL/L）以测试外周胰岛素敏感性（葡萄糖输注率）。还通过间接测热法评估碳水化合物（CHOOX）和脂肪氧化（FOX）以及非氧化葡萄糖处置（NOGD）。测量血浆三羧酸（TCA）循环中间产物、AA 和酰基辅酶 A 以及最大摄氧量和身体成分（DXA）。
结果
两组在年龄、BMI、去脂体重、最大摄氧量或 ATP III 标准方面无统计学差异。然而，早型与晚型相比，外周胰岛素敏感性更高（P=0.009），HOMA-IR（P=0.02）和 Adipose-IR（P=0.05）更低。此外，早型的 NOGD 更高（P=0.008），胰岛素刺激的 CHOOX 更高（P=0.02）。虽然空腹乳酸（P=0.01）、TCA 中间产物（异柠檬酸、α-酮戊二酸、琥珀酸、富马酸、苹果酸；均 P≤0.04）和一些 AA（脯氨酸、异亮氨酸；P=0.003-0.05）在早型中较低，但其他 AA（苏氨酸、组氨酸、精氨酸；均 P≤0.05）和大多数酰基辅酶 A 较高（P≤0.05）与晚型相比。
结论
与晚型相比，早型中更高的胰岛素敏感性和代谢灵活性与血浆 TCA 浓度有关。
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