Altered Glucose Kinetics Occurs With Aging

Abstract

Metabolic flexibility is the ability to respond or adapt to conditional changes in metabolic demand. The purpose of our study was to determine how age affects metabolic flexibility and underlying glucose kinetics in young and older healthy adults. We hypothesized that in response to a glucose challenge: 1) young participants would exhibit greater glucose clearance than older participants, and 2) young participants would have decreased endogenous glucose production via gluconeogenesis. Glucose and lactate tracers, along with gas exchange data were used to measure glucose kinetics and respiratory exchange ratios (RER=VCO2/VO2) to determine metabolic flexibility during a 2-hour 75-gram oral glucose tolerance test (OGTT). After a 12-hour 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) individuals received venous primed continuous infusions of [6,6-2H]glucose, and [3-13C]lactate with a H13CO3− bolus. Following a 90-minute metabolic stabilization and tracer equilibration period, volunteers underwent an OGTT. In all study participants arterialized glucose concentrations ([glucose]) rose 15 minutes post-glucose consumption, peaked at 60 minutes, and remained elevated. Older individuals had sustained increases in [glucose] compared to the young. As assessed by rates of appearance (Ra), disposal (Rd) and metabolic clearance (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 during the OGTT. Lastly, there were no differences in RER between young and older volunteers, making RER an incomplete measure of metabolic flexibility in volunteers studied. Our study revealed that glucose kinetics are significantly altered in an aged population following a glucose challenge. Further, these physiological deficits are not detected from changes in RER during an OGTT. Supported by NIH grant R01 AG059715 to GAB. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.