Factors responsible for development from normal glucose tolerance to isolated postchallenge hyperglycemia

OBJECTIVE - isolated postchallenge hyperglycemia UPH), defined as fasting plasma glucose (FPG) level <7.0 mmol/l and 2-h plasma glucose (PG) level ≥ 11.1 mmol/l, is a subtype of early-stage diabetes. This study evaluates the metabolic profiles of insulin secretion and insulin sensitivity in IPH to clarify the factors responsible for development of this form of type 2 diabetes. RESEARCH DESIGN AND METHODS - We conducted cross-sectional analysis of 231 Japanese men aged 20-70 years. The subjects were classified into the following three groups, based on the results of a 75-g oral glucose tolerance test (OGTT): 1) normal glucose tolerance (NGT), defined as FPG level <6.1 mmol/l and 2-h PG level <7.8 mmol/l (n = 89); 2) impaired glucose tolerance (IGT), defined as FPG level <7.0 mmol/l and 2-h PG level of 7.8-11.1 mmol/l (n = 94); and 3) IPH (n = 48). We compared the three groups for insulin secretion (insulinogenic index) and insulin sensitivity (index of insulin resistance using homeostasis model assessment [HOMA-IR]). RESULTS - The insulmogenic index in IPH was the lowest of the three groups (P < 0.001 versus NGT). The HOMA-IR in the IGT and IPH groups were significantly higher than in the NGT group (P < 0.001), but both were similar. By linear regression analysis, the insulinogenic index rather than fasting insulin or HOMA-IR was the more significant factor in the 2-h PG level in IGT and IPH. CONCLUSIONS - Subjects with IPH exhibited distinctly impaired early-phase insulin secretion and only mild insulin resistance, indicating that reduced insulin secretion is the primary determinant of deterioration from NGT to IGT and IPH in development of type 2 diabetes in these subjects.