Influence of Ageing on Glucose Homeostasis*

Abstract

The mechanism of age-related glucose intolerance 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 concentrations 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 affinity 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 observed 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 increasing 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 intolerance. At similar glucose and insulin concentrations, peripheral 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)

Carbohydrate metabolism in the elderly

“…This study is in agreement with other studies where several insulin doses were employed Fink et al, 1983). In addition, studies using various techniques, including the hyperglycemic clamp Elahi et al, 1993), the forearm glucose uptake technique (Jackson et al, 1982) and Min Mod (Chen et al, 1985) have revealed resistance to insulin-induced glucose disposal in aged volunteers. It is obvious that in addition to age various factors in¯uence insulin sensitivity including fat mass, fat distribution, physical ®tness, dietary composition and genetic factors.…”

The Relationship of Fasting Plasma Glucose Values and Other Variables to 2-h Postload Plasma Glucose in Japanese Subjects

“…In this context, the impairment of glucose tolerance with aging has been confirmed by numerous previous studies indicating that this decline in glucose tolerance, which begins in the third decade, continues throughout adulthood (11,24,25). These age-related changes particularly characterize the impaired response to glucose challenge rather than FPG, partly due to physical inactivity (26) and potentially associated with a decrease in muscle mass.…”

“…These age-related changes particularly characterize the impaired response to glucose challenge rather than FPG, partly due to physical inactivity (26) and potentially associated with a decrease in muscle mass. In more recent estimations based on arterialized venous plasma, the age-related increase in glucose concentrations from 60 to 180 min after a 100-g oral glucose load averaged 13-14 mg/dl per decade (25). These reports agreed with our results, which showed a mean increase of 9.4 mg/dl per decade between the ages of 30 and 78 years (r ϭ 0.68, P Ͻ 0.0001) in the values for 2-h PG at FPG 126 mg/dl.…”

Lipid metabolism in the elderly

“…Substrate availability is not a likely explanation since free fatty acid release is similar or higher during exercise and following a meal in older compared to younger individuals (Jackson et al, 1982;Sial et al, 1996). Thus, in older individuals, it would appear as if the respiring tissue mass did not respond to increased free fatty acid availability by increasing fat oxidation.…”