Mechanism of Increased Plasma Glucose Levels after Oral Glucose Ingestion in Normal-Weight Middle-Aged Subjects

Abstract

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 ¹³C-enriched corn starch glucose. Glucose levels, substrate oxidation (indirect calorimetry) and exogenous glucose oxidation (¹³C enrichment of expired CO₂) 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.