Influence of Ageing OH Glucose Homeostasis

Abstract

The mechanism of age-related glucose intoler- ance was investigated by comparing forearm glucose uptake (FGU) during 100-g oral glucose tolerance tests (GTTs) in healthy men of different ages: group Y, 19-24 yr (n = 11); group M, 30-45 yr (n = 12); and group E, 70-83 yr (n = 9). Progressive elevation of the glucose tolerance curve occurred with increasing age, the curve of each group differing from the others at all points from 60-180 min. Although with age absolute levels of FGU were not reduced, the rise in FGU per incremental change in arterial plasma glucose concentration was significantly decreased, whereas the corresponding relationship between FGU and serum insulin was less marked. Early insulin responses were similar in all age groups, but after 60 min the curves diverged in a pattern corresponding to the respective glucose responses and differed significantly from 150-180 min. The relative changes in insulin levels corresponded to those observed in C-peptide con- centrations in all groups. C-peptide to insulin ratios were not influenced by age. Similar proportions of proinsulin in total immunoreactive insulin were found in elderly subjects and men from group M. No difference in monocyte insulin receptor numbers or affin- ity was observed in elderly men and subjects from group M. Basal FFA levels were significantly higher in the elderly than in group Y and fell rapidly after glucose loading in all groups. Arterial lactate concentrations increased after glucose loading in all groups, but in the elderly the rise was significantly delayed. In order to compare FGU in these groups at similar arterial glucose levels rather than at the differing concentrations ob- served after glucose loading, GTTs were repeated in five subjects from group M. During these studies additional glucose was infused intermittently from 30-180 min in order to simulate the raised arterial glucose concentrations noted in the elderly. This required a mean infusion of 62.3 g (range, 33.4-97.7 g) and increased FGU to a level 3-fold greater than that observed in the elderly. To determine whether any reserve for further in- creasing overall glucose disposal is retained in the elderly, GTTs were repeated in three older men, in each of whom additional glucose infusions raised the 60-min concentrations by 50 mg/dl. In each of these subjects the subsequent fall in arterial glucose levels was accelerated. The results suggest that impaired peripheral glucose uptake is an important mechanism resulting in age-related glucose in- tolerance. At similar glucose and insulin concentrations, periph- eral glucose uptake in the elderly is only one-third that in younger men. Since insulin receptor binding was not reduced in the elderly, this impairment may be a postreceptor phenomenon. (J Clin Endocrinol Metab 55: 840, 1982)