Factors responsible for age-related elevation in fasting plasma glucose: a cross-sectional study in Japanese men

To evaluate the factors associated with age-related increase in fasting plasma glucose (FPG) in Japanese men with normal fasting glucose, we measured FPG, fasting immunoreactive insulin, glycated hemoglobin, total cholesterol, triglyceride, and high-density lipoprotein cholesterol levels in health check examinees. Subjects with FPG less than 6.1 mmol/L together with glycated hemoglobin less than 5.6% were enrolled in the study. The homeostasis model assessment of insulin resistance (HOMA-IR) and HOMA-beta were used as the indices of insulin sensitivity and insulin secretion, respectively. Fasting plasma glucose increased significantly with age (r = 0.30, P < .0001), and HOMA-beta decreased significantly with age (r = 0.24, P < .0001). The HOMA-IR had no significant relation with age (r = 0.06, not significant), whereas body mass index and serum triglyceride were associated with HOMA-IR (r = 0.49, P < .0001 and r = 0.33, P < .0001, respectively). Thus, in Japanese male subjects with normal fasting glucose, it is suggested that the FPG increment with age is associated with decreased beta-cell function rather than with insulin resistance. Further analyses were performed by comparing 3 groups: low FPG (FPG <5.0 mmol/L), high FPG (5.0 < or = FPG < 5.6 mmol/L), and mild impairment of fasting glycemia (mild IFG) (5.6 < or = FPG < 6.1 mmol/L). The insulin levels in mild IFG and high FPG were significantly higher than in low FPG (P < .001), but those in mild IFG were similar to those in high FPG. Analysis of the 3 subgroups revealed that, whereas insulin sensitivity was impaired more in high FPG, there was little compensatory increase in insulin in mild IFG, suggesting that beta-cell function is already deteriorated when the FPG level is greater than 5.6 mmol/L.