Improvement of insulin resistance by a new insulin secretagogue, nateglinide--analysis based on the homeostasis model.
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 beta-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-beta, 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.
Diabetes Care Division, Department of Internal Medicine, Mitsui Memorial Hospital, Kanda-Izumi-cho 1, Chiyoda-ku, Tokyo 1018643, Japan. tshiba@mitsuihosp.or.jp
Teruo
T
Shiba
D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D003510:Cyclohexanes / Q000627:therapeutic use*; D006442:Glycated Hemoglobin / Q000032:analysis; D006706:Homeostasis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D000078790:Insulin Secretion; D007700:Kinetics; D008875:Middle Aged; D008954:Models, Biological; D000077715:Nateglinide; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000627:therapeutic use*; D012044:Regression Analysis
D001786:Blood Glucose; D003510:Cyclohexanes; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D000077715:Nateglinide; D010649:Phenylalanine