Adverse effects of obesity on β-cell function in Japanese subjects with normal glucose tolerance

The purpose of the present study was to elucidate the role of obesity in both early- and late-phase insulin secretion during an oral glucose tolerance test (OGTT) performed with 75 g glucose in Japanese subjects. This was performed using indices of β-cell function adjusted for insulin sensitivity. Of 155 subjects assessed, 68 had normal glucose tolerance (NGT) and 87 had impaired glucose tolerance (IGT). We used the homeostasis model assessment-insulin resistance (HOMA-IR) index as an indicator of insulin sensitivity. As indicators of β-cell function, we used the HOMA-β index, an insulinogenic index (ΔI₃₀/ΔG₃₀), and ΔAUC I/G_(0-120), which were obtained in the OGTT. We then reevaluated the results after adjusting the β-cell function for insulin sensitivity ([ΔI₃₀/ΔG₃₀]/HOMA-IR index and [ΔAUC I/G_(0-120)]/HOMA-IR index). β-Cell function was observed to reduce as the glucose tolerance deteriorated from NGT to IGT. However, when the effects of obesity were considered, the obese subjects with NGT already showed a decline in the (ΔAUC I/G_(0-120))/HOMA-IR index value when compared with the nonobese subjects with NGT, despite the fact these subjects did not differ with regard to (ΔI₃₀/ΔG₃₀)/HOMA-IR index. As the glucose tolerance deteriorated to IGT, both (ΔI₃₀/ΔG₃₀)/HOMA-IR index and (ΔAUC I/G_(0-120))/HOMA-IR index decreased to an identical extent in both subgroups. These data indicate that obesity causes a decrease in insulin secretion, especially during the late phase following a glucose load, even if the glucose tolerance remains normal.