Fasting tests of insulin secretion and sensitivity predict future prediabetes in Japanese with normal glucose tolerance

Aims/Introduction: Reduced insulin sensitivity and secretion are important in the pathogenesis of type 2 diabetes. Their relationships to prediabetes, impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) have been previously studied with the oral glucose tolerance test (OGTT). We investigated whether or not baseline measures of insulin secretion and sensitivity obtained from fasting blood specimens were related to the development of prediabetes and how these measures compared with those based on the OGTT. Materials and Methods: In 152 Japanese subjects with normal glucose tolerance, we measured baseline plasma glucose and insulin after an overnight fast and during a 75 g OGTT, insulin resistance index (homeostasis model assessment [HOMA-IR]), and insulin secretion (insulinogenic index [30 min insulin - fasting insulin] divided by [30 min glucose - fasting glucose] or HOMA-beta). Results: At a 5-6 year (mean 5.7 years) follow-up examination, we confirmed 36 cases of prediabetes. After adjusting for age, sex, family history of diabetes, body mass index, and 2-h plasma glucose, the odds ratio comparing the lowest tertile (<= 0.82) of insulinogenic index with the highest tertile (>= 1.43) was 6.98 (95% confidence interval, 1.96-24.85) and was 10.72 (2.08-55.3) comparing the lowest tertile (<= 76.3) of HOMA-beta with the highest tertile (>= 122.1), whereas the respective odds ratios of HOMA-IR were 3.74 (1.03-13.57) and 10.89 (1.93-61.41) comparing the highest tertile (>= 1.95) with the lowest tertile (<= 1.25). Conclusions: Lower insulin secretion and sensitivity are independent risk factors for prediabetes. Clinically practical identification of those at risk for prediabetes is obtainable from HOMA-beta and HOMA-IR, both of which are measured in fasting state. (J Diabetes Invest, doi: 10.1111.j.2040-1124.2010.00041.x, 2010)