Improvement of insulin resistance by a new insulin secretagogue, nateglinide—analysis based on the homeostasis model

Abstract

Type 2 diabetes is a heterogeneous disorder characterized by defects in the early phase of insulin secretion after meals and in insulin resistance at its early stage. A new insulin secretagogue, nateglinide, has been shown to elicit an acute insulin release and to reduce postprandial hyperglycemia. We have treated 30 patients with type 2 diabetes using nateglinide and performed a standard meal test at breakfast, both before and after the treatment. Insulin resistance and β-cell function was assessed by the HOMA model. Nateglinide, at 1 and 2 h after the test meal, significantly stimulated postprandial insulin secretion by 62.0 and 41.0% and improved blood glucose values by 17.3 and 21.9%, respectively, after the treatment. Fasting blood glucose (FBG) and glycohemoglobin was significantly reduced by 9.8 and 10.3%, respectively. The reduction was significantly larger in postprandial glucose than in FBG ( P<0.0005). A significant correlation was found in the HOMA-insulin resistant (IR) index and in the changes of fasting IRI. When the patients were divided into three groups, forming a markedly insulin resistant (MIR) group, an IR group and a non-insulin resistant (NIR) group, HOMA-IR levels improved significantly, from 7.0±4.3 to 4.5±2.8 ( P=0.026) in the MIR group and showed a tendency toward improvement in the IR group, from 2.9±0.7 to 2.3±1.1 ( P=0.062), but failed to exhibit such a positive response in the NIR group, changing from 1.2±0.2 to 1.9±0.9 ( P=0.21). HOMA-β, on the other hand, improved significantly in the NIR group only, from 16.4±7.8 to 26.9±9.9 ( P=0.017), but not in the IR nor MIR groups (M±S.D.). In conclusion, nateglinide improved the excessive excursion of postprandial glucose by the augmentation of early insulin secretion after a meal and differentially affected fasting insulin levels and HOMA-IR indexes, depending on the degree of insulin resistance.