Influence of aging on hepatic and peripheral glucose metabolism in humans.

Mechanisms of glucose intolerance with aging were studied by comparing the metabolic response to glucose ingestion in 10 young (20-23 yr) and 10 elderly (73-80 yr) normal men with the simultaneous application of the forearm and double-isotope techniques. The latter technique consisted of a primed-constant infusion of [3-3H]glucose followed by the administration of an oral glucose load (mean +/- SE, 90.7 +/- 0.7 g) containing [1-14C]glucose. Fasting plasma glucose and insulin concentrations were similar in young and elderly subjects, but in the elderly, glucose tolerance was markedly impaired. Although in the elderly the initial rise in insulin levels (delta, i.e., the incremental area under the curve) from 0 to 30 min was delayed (P less than .02), the response from 0 to 45 min, 0 to 60 min, and thereafter equaled that in the young group, and from 90 to 240 min insulin concentrations in the elderly exceeded those in young subjects. Basal hepatic glucose output (HGO) was similar in young and elderly men (2.13 +/- 0.10 and 1.97 +/- 0.14 mg.kg-1.min-1, respectively). Similar proportional reductions in HGO from 0 to 270 min after glucose loading occurred in young (59.7 +/- 10.3%) and elderly (50.3 +/- 4.9%) subjects but was delayed in the elderly. Suppression of HGO was observed in the young 30 min after glucose ingestion (P less than .02), but not before 60 min in the elderly subjects (P less than .05). The systemic appearance of ingested glucose (0-270 min) was slowed with age (80.7 +/- 3.1 and 66.9 +/- 4.3% of the oral load in the young and elderly groups, respectively; P less than .02). Initial increments in both total glucose disappearance (Rd) and forearm glucose uptake (FGU) from 0 to 60 min after glucose loading were decreased in the elderly (Rd, 4.1 +/- 0.7 vs. 11.5 +/- 1.3 g, P less than .001; FGU, 17.2 +/- 1.4 vs. 24.6 +/- 2.5 md/dl forearm, P less than .02). The overall increment (delta, 0-270 min) in Rd was reduced with age (47.2 +/- 2.9 and 34.5 +/- 3.6 g, P less than .02 in the young and elderly, respectively), but the corresponding data for FGU were similar in the two groups.(ABSTRACT TRUNCATED AT 400 WORDS)