Mechanism of increased plasma glucose levels after oral glucose ingestion in normal-weight middle-aged subjects

Background/aims: To determine the decline in glucose tolerance in normal-weight middle-aged subjects, we performed a cross-sectional study using double-labelled oral glucose tolerance tests in 8 middle-aged (46.3 +/- 0.9 years) and in 8 young (23.6 +/- 0.5) subjects with similar normal body weight.

Methods: Plasma glucose was labelled by an infusion of dideuterated glucose started 120 min before ingestion of 1 g/kg of naturally (13)C-enriched corn starch glucose. Glucose levels, substrate oxidation (indirect calorimetry) and exogenous glucose oxidation ((13)C enrichment of expired CO(2)) were monitored for 330 min.

Results: In the middle-aged subjects, the appearance of exogenous glucose was reduced (723 +/- 52 mg/kg/330 min) compared to young subjects (864 +/- 38; p < 0.05), and systemic glucose production was normal. Plasma glucose levels were increased due to a reduced glucose disappearance rate (middle aged: 1,046 +/- 61 mg/kg/330 min vs. young 1,242 +/- 67; p < 0.05), concerning both oxidative and non-oxidative disposal. This reduction was no longer apparent when the results were normalized for fat-free mass. Insulin levels were similar in young and middle-aged subjects.

Conclusion: In normal-weight middle-aged individuals, glucose intolerance is mainly due to the reduction in the mass of fat-free glucose-utilizing tissues. The higher plasma glucose levels enable normal glucose supply to peripheral tissues, and increase splanchnic glucose uptake.