Delayed Enteral Postprandial Lactate Shuttling In Older Healthy Men And Women

Insulin resistance, obesity, sedentary behavior, and type 2 diabetes have been linked to metabolic inflexibility which is the inability to switch substrates based on energy demand. Lactate, a product of glycolysis, is formed under aerobic conditions, is a major energy source, gluconeogenic precursor, and signaling molecule. Extensive work has been done in young and exercising humans; however the effect of age on lactate metabolism in the postprandial period is not known. PURPOSE: To understand the effects of aging on lactate kinetics utilizing isotopically labeled [3-13C]lactate in young and older healthy men and women. METHODS: Fifteen young and 13 older healthy men and women received primed-continuous infusions of [3-13C]lactate and underwent a 75 g, oral D-glucose challenge. Arterialized blood samples were taken before and 5, 15, 30, 60, 90, and 120 minutes post glucose challenge. Blood lactate concentrations ([lactate]), rates of appearance (Ra), disappearance (Rd), and metabolic clearance (MCR) were measured. Age comparisons were made using two-way ANOVA with repeated measures. Data are presented as Mean ± SEM. RESULTS: Arterial [lactate] peaked at 15 min in both young and older participants (1.09 ± 0.35 vs. 0.98 ± 0.30, respectively). No differences in blood [lactate] between age groups were evident. Tracer-measured lactate Ra and Rd peaked at 15 min in the young and remained elevated. Both Ra and Rd were delayed in older, reaching their peak at 90 min. Thus, the 15 min lactate Ra and Rd of young was significantly higher than that of the older participants (Ra: 3.19 ± 0.78 vs. 2.32 ± 0.65, p = 0.004; Rd: 2.97 ± 0.53 vs. 2.30 ± 0.83, p = 0.02). No differences in MCR were observed. CONCLUSIONS: The purpose was to investigate the effects of age on lactate kinetics, which may help indicate metabolic inflexibility. Our data revealed a delayed lactate Ra and Rd in older healthy men and women, peaking at 90 minutes after the oral glucose challenge. Their young counterparts peaked at 15 minutes post-challenge. This study is the first to reveal a suppression in lactate kinetics post glucose challenge in older healthy individuals, suggesting an effect of age on the Postprandial Lactate Shuttle and may indicate metabolic inflexibility. Future work can help elucidate and contribute to our understanding of aging metabolic inflexibility. R01AG059715