Relative Contribution of Insulin Secretion and Sensitivity at Different Stages of Glucose Tolerance: Non-obese versus Obese Japanese Subjects

Abstract

We examined the relative contribution of insulin secretion and insulin sensitivity at different stages of glucose tolerance in non-obese and obese Japanese subjects. A total of 641 subjects who underwent 75-g glucose tolerance testing were divided into two groups: 436 non-obese subjects (body mass index: BMI <25) and 205 obese subjects (BMI ≥25). The subjects were further divided into four groups: those with normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and diabetes. We compared insulin secretion and sensitivity indices, such as the insulinogenic index (IGI), homeostatic model insulin resistance (HOMA-IR), homeostatic model assessment of β-cell (HOMA-β) and insulin sensitivity index (ISI). In a univariate analysis, the obese subjects had higher levels of HOMA-IR, HOMA-β and IGI associated with lower ISI values in comparison with that observed in the non-obese subjects at different stages of glucose tolerance. A multiple logistic regression analysis showed that the HOMA-IR was a significant independent factor between the non-obese and obese subjects; the odds ratio (OR) (95% confidential interval: CI) was 3.78 (2.04-7.01; p<0.01) in the NGT group, 4.91 (2.06-11.72; p<0.01) in the IGT group and 2.02 (1.22-3.34; p<0.01) in the diabetes group. Although a similar trend was also observed in the IFG group (OR=15.83), the difference did not reach a level of statistical significance (p=0.066). These data suggest that obese subjects are characterized by increased insulin resistance rather than reduced insulin secretion at all stages of glucose tolerance. Therefore, non-obese subjects and obese subjects are distinct entities at all stages of glucose tolerance.