Effect of age on peripheral tissue glucose utilization

Muscle is the primary sink for glucose uptake as adipose tissue is relatively inert and accounts for only 2—3% of glucose uptake (DeFronzo 1981). Brain and the splanchnic bed account for another 20—55% (DeFronzo 1988). The latter two sinks for glucose uptake are insulin independent. The majority of reports examining the role of age on glucose uptake, utilizing a variety of techniques (clamp, MinMod, local forearm perfusion, glucose—insulin—somatostatin infusion) have demonstrated decreased insulin sensitivity during hyperinsulinaemia as summarized in the report by EGIR (Ferrannini et al 1996).

However, this decreased insulin sensitivity is not demonstrated for fasting insulin levels (Coon et al 1989). The EGIR report is an analysis of euglycaemic clamps, at a single dose of 240 pmol'm72 'min71, from 20 European clinical research centres. In this study a total of 1146 clamps were performed (776 men and 380 women) for 2 h in individuals with normal glucose tolerance and arterial blood pressure. In addition, anthropometric data were available. Glucose utilization, M, was calculated during the last 40 min of the study. In univariate analysis, age was associated with a significant decrease in insulin action of (P = 0.0002) 0.9 mmol'kg71 per decade of life, (*0.2mg'kg71 per decade of life) which was no longer significant when adjusted for BMI (P = 0.08). However, BMI was strongly associated with a decrease in insulin action (5 mmol' kg 71' 10 kg of body weight, 0.9mg'kg71' 10kg of body weight, P<0.001), which remained significant, even after adjustment for age. Furthermore, when the relationship of glucose utilization, M, was examined as a function of gender and obesity (BMI 425 or >25), age-related decrease in insulin action was demonstrated only in lean women (cf. Fig. 3 of Ferrannini et al 1996), without a slope change after age 50 years (i.e. no menopause effect). Thus, this large study demonstrates that glucose uptake is not altered as a function of age per se except in lean women at this hyperinsulinaemic level.

Despite the strength of the EGIR study, the issue of age-related insulin resistance is still controversial, because it has been argued that complete dose-response curves are necessary to resolve the issue. Several groups have conducted dose-response studies as a function of age. The studies are rather small («~50), mainly in men, without a significant difference in BMI between young and old. One study (Rowe et al 1983) has examined the effect of age on glucose utilization over the insulin range of 60—6000 pmol/l (10—1000 mU/ml). An age-associated decrease in glucose utilization was demonstrated with preservation of maximal glucose uptake (i.e. a shift to the right). The half-maximal glucose uptake occurred when plasma insulin levels were 324 pmol/l (54 mU/ml) in the young and 678 pmol/l (113 mU/ml) in the old. When the glucose utilization was plotted per kilogram of lean body mass, the relationship remained. This study is in agreement with other studies where several insulin doses were employed (DeFronzo 1979, Fink et al 1983). In addition, studies using various techniques, including the hyperglycaemic clamp (DeFronzo 1979, Elahi et al 1993), the forearm glucose uptake technique (Jackson et al 1982) and Minimal Model (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 influence insulin sensitivity including fat mass, fat distribution, physical fitness, dietary composition and genetic factors. When these factors are taken into account, it is not clear that age per se still has an independent effect on peripheral glucose uptake.

0 0

Post a comment