Exercise Physiology Laboratory, Department of Integrative Biology, University of California, Berkeley, California, United States.
Department of Endocrinology, School of Medicine, University of California, San Francisco, California, United States.
Am J Physiol Endocrinol Metab. 2024 Aug 1;327(2):E217-E228. doi: 10.1152/ajpendo.00091.2024. Epub 2024 Jun 19.
Our purpose was to determine how age affects metabolic flexibility and underlying glucose kinetics in healthy young and older adults. Therefore, glucose and lactate tracers along with pulmonary gas exchange data were used to determine glucose kinetics and respiratory exchange ratios [RER = carbon dioxide production (V̇co)/oxygen consumption (V̇o)] during a 2-h 75-g oral glucose tolerance test (OGTT). After an 12-h overnight fast, 28 participants, 15 young (21-35 yr; 7 men and 8 women) and 13 older (60-80 yr; 7 men and 6 women), received venous primed-continuous infusions of [6,6-H]glucose and [3-C]lactate with a [Formula: see text] bolus. After a 90-min metabolic stabilization and tracer equilibration period, volunteers underwent an OGTT. Arterialized glucose concentrations ([glucose]) started to rise 15 min post glucose consumption, peaked at 60 min, and remained elevated. As assessed by rates of appearance (Ra) and disposal (Rd) and metabolic clearance rate (MCR), glucose kinetics were suppressed in older compared to young individuals. As well, unlike in young individuals, fractional gluconeogenesis (fGNG) remained elevated in the older population after the oral glucose challenge. Finally, there were no differences in 12-h fasting baseline or peak RER values following an oral glucose challenge in older compared to young men and women, making RER an incomplete measure of metabolic flexibility in the volunteers we evaluated. Our study revealed that glucose kinetics are significantly altered in a healthy aged population after a glucose challenge. Furthermore, those physiological deficits are not detected from changes in RER during an OGTT. To determine metabolic flexibility in response to an OGTT, we studied healthy young and older men and women to determine glucose kinetics and changes in RER. Compared to young subjects, glucose kinetics were suppressed in older healthy individuals during an OGTT. Surprisingly, the age-related changes in glucose flux were not reflected in RER measurements; thus, RER measurements do not give a complete view of metabolic flexibility in healthy individuals.
我们的目的是确定年龄如何影响健康的年轻和老年成年人的代谢灵活性和潜在的葡萄糖动力学。因此,在 2 小时 75 克口服葡萄糖耐量试验(OGTT)期间,使用葡萄糖和乳糖尿液示踪剂以及肺气体交换数据来确定葡萄糖动力学和呼吸交换比 [RER=二氧化碳产生(V̇co)/氧气消耗(V̇o)]。在 12 小时禁食过夜后,28 名参与者,15 名年轻(21-35 岁;7 名男性和 8 名女性)和 13 名老年(60-80 岁;7 名男性和 6 名女性)接受了静脉推注持续输注[6,6-H]葡萄糖和[3-C]乳糖尿液,并给予[Formula: see text]bolus。在 90 分钟的代谢稳定和示踪剂平衡期后,志愿者进行了 OGTT。动脉化葡萄糖浓度[glucose]在葡萄糖消耗后 15 分钟开始上升,在 60 分钟时达到峰值,并保持升高。如通过出现率(Ra)和处置率(Rd)和代谢清除率(MCR)评估,葡萄糖动力学在老年个体中受到抑制。此外,与年轻个体不同,在口服葡萄糖挑战后,老年人群中的部分糖异生(fGNG)仍然升高。最后,在口服葡萄糖挑战后,老年男性和女性的 12 小时空腹基线或峰值 RER 值没有差异,使得 RER 成为我们评估的志愿者代谢灵活性的不完全衡量标准。我们的研究表明,在健康的老年人群中,口服葡萄糖挑战后葡萄糖动力学发生显著改变。此外,在 OGTT 期间,RER 的变化并未检测到这些生理缺陷。为了确定 OGTT 反应的代谢灵活性,我们研究了健康的年轻和老年男性和女性,以确定葡萄糖动力学和 RER 的变化。与年轻受试者相比,在 OGTT 期间,老年健康个体的葡萄糖动力学受到抑制。令人惊讶的是,葡萄糖通量的年龄相关变化在 RER 测量中没有反映出来;因此,RER 测量不能全面了解健康个体的代谢灵活性。