Fat Accumulation and Elevated Free Fatty Acid Are Associated With Age-Related Glucose Intolerance: Bunkyo Health Study

Context: Older adults have a high prevalence of new-onset diabetes, often attributed to age-related decreases in insulin sensitivity and secretion. It remains unclear whether both insulin sensitivity and secretion continue to deteriorate after age 65.

Objective: To investigate the effects of aging on glucose metabolism after age 65 and to identify its determinants.

Methods: This cross-sectional study involved 1438 Japanese older adults without diabetes. All participants underwent a 75-g oral glucose tolerance test (OGTT). Body composition and fat distribution were measured with dual-energy X-ray absorptiometry and magnetic resonance imaging. Participants were divided into 4 groups by age (65-69, 70-74, 75-79, and 80-84 years) to compare differences in metabolic parameters.

Results: Mean age and body mass index were 73.0 ± 5.4 years and 22.7 ± 3.0 kg/m². The prevalence of newly diagnosed diabetes increased with age. Fasting glucose, fasting insulin, the area under the curve (AUC)-insulin/AUC-glucose and insulinogenic index were comparable between groups. AUC-glucose and AUC-insulin during OGTT were significantly higher and Matsuda index and disposition index (Matsuda index · AUC-insulin/AUC-glucose) were significantly lower in the age 80-84 group than in the age 65-69 group. Age-related fat accumulation, particularly increased visceral fat area (VFA), and elevated free fatty acid (FFA) levels were observed. Multiple regression revealed strong correlations of both Matsuda index and disposition index with VFA and FFA.

Conclusion: Glucose tolerance declined with age in Japanese older adults, possibly due to age-related insulin resistance and β-cell deterioration associated with fat accumulation and elevated FFA levels.