Beneficial effects of nateglinide on insulin resistance in type 2 diabetes

https://doi.org/10.1016/j.diabres.2005.08.004Get rights and content

Abstract

Nateglinide, a rapid insulin secretagogue, is known to facilitate the early phase of insulin secretion and has been used for the treatment of type 2 diabetic patients with postprandial hyperglycemia. The aim of this study is to evaluate the effect of nateglinide on insulin resistance as well as insulin secretory defects in type 2 diabetic patients. Insulin secretion ability was evaluated by the hyperglycemic clamp test, and insulin sensitivity was evaluated by the euglycemic hyperinsulinemic clamp test, using an artificial pancreas. The hyperglycemic clamp test showed that a 7-day treatment with nateglinide significantly increased insulin secretion in response to high glucose. Interestingly, although nateglinide is known to facilitate insulin secretion, daily urinary C-peptide excretion was decreased after nateglinide treatment. Moreover, in the euglycemic hyperinsulinemic clamp test, glucose infusion rate was significantly increased by nateglinide treatment, indicating that nateglinide functions to decrease insulin resistance. Nateglinide ameliorates insulin resistance as well as insulin secretory defects in type 2 diabetic patients.

Introduction

Insulin secretory defects and insulin resistance due to hereditary and/or environmental factors are observed in type 2 diabetic patients. To date, insulin secretagogues, insulin sensitizers and insulin injections have been used for the treatment of type 2 diabetic patients. It was reported that postprandial hyperglycemia is an independent risk factor of cardiovascular disease (DECODE study) [1], and that the improvement of postprandial hyperglycemia by an α-glucosidase inhibitor decreased the risk of death (STOP-NIDDM) [2]. An important cause of postprandial hyperglycemia is impairment of the early phase of insulin secretion [3]. Nateglinide, a rapid insulin secretagogue, facilitates the early phase of insulin secretion [4] and has been used for the treatment of type 2 diabetic patients with postprandial hyperglycemia. However, the effect of nateglinide on insulin resistance remained unknown. In this study, we examined the effect of nateglinide on insulin resistance as well as insulin secretory defects in type 2 diabetic patients.

Section snippets

Methods

We recruited seven Japanese inpatients in Osaka University Hospital with type 2 diabetes for this study after obtaining written informed consent. The study was approved by the Ethics Committee for Human's Studies at Osaka University Hospital. These patients were treated with a standard diet (27–29 kcal/kg), exercise (approximately 10,000 steps per day) and low dose insulin (less than seven units per day) for 3 weeks to reduce the influence of glucose toxicity on glucose metabolism and insulin

Statistical analysis

Statistical comparisons between before and after treatment with nateglinide were assessed using Student's paired two-tailed t-test. Multiple comparisons among before and after nateglinide treatment, and healthy control subjects were tested using the one-way analysis of variance (ANOVA). These comparisons were performed on a personal computer with Statview SE (Brainpower, Calabasas, CA, USA). A p-value of less than 0.05 was considered statistically significant.

Results and discussion

Clinical characteristics and metabolic parameters of the type 2 diabetic patients used in this study are as follows: age 56.0 ± 3.5 years, duration 4.7 ± 2.1 years, body mass index (BMI) 23.0 ± 1.8, hemoglobin A1C (HbA1C) 9.0 ± 2.2%, fasting plasma glucose 117 ± 15 mg/dl. All subjects were classified into diabetes category based on the criteria proposed by the American Diabetes Association. The insulinogenic index, an indicator of the early phase of insulin secretion, which is determined by a 75 g oral

Acknowledgments

We appreciate the excellent technical assistance of Y. Sasaki and the outstanding secretarial work of C. Yokogawa.

References (12)

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