PPARα Agonist Fenofibrate Reduced the Secreting Load of β-Cells in Hypertriglyceridemia Patients with Normal Glucose Tolerance.

Jia Liu,Ning Yang,Jing Fu,Ying Wang,Yumei Jia,Yanjin Hu,Rui Lu,Guang Wang

doi:10.1155/2016/6232036

Abstract

Hypertriglyceridemia is an important risk factor associated with insulin resistance and β-cell dysfunction. This study investigated the effects of hypertriglyceridemia and fenofibrate treatment on insulin sensitivity and β-cell function in subjects with normal glucose tolerance. A total of 1974 subjects with normal glucose tolerance were divided into the normal TG group (NTG group, n = 1302) and hypertriglyceridemia group (HTG group, n = 672). Next, 92 patients selected randomly from 672 patients with hypertriglyceridemia were assigned to a 24-week fenofibrate treatment. The HTG group had increased waist circumference (WC), body mass index (BMI), homeostasis model assessment of insulin resistance (HOMA-IR), and homeostasis model assessment of β-cell function (HOMA-β) and decreased high-density lipoprotein cholesterol (HDL-C) compared with the NTG group (all P < 0.01). The 24-week fenofibrate treatment significantly decreased the WC, BMI, TG, HOMA-IR, and HOMA-β levels and increased the HDL-C levels in the patients with hypertriglyceridemia (WC, BMI, and HOMA-IR: P < 0.05; TG, HDL-C, and HOMA-β: P < 0.01). The fenofibrate treatment significantly alleviated insulin resistance and reduced the secreting load of β-cells in the hypertriglyceridemia patients with normal glucose tolerance.

Highlights

Type 2 diabetes is a growing health issue due to its increased prevalence and lack of an ideal therapy [1]
We aimed to investigate the effects of hypertriglyceridemia and fenofibrate treatment on insulin sensitivity and β-cell function in subjects with normal glucose tolerance
Hypertriglyceridemia was defined by a plasma TG level ≥1.7 mmol/L according to the guideline of NCEP ATP III and the Endocrine Society [12, 13]

Summary

Introduction

Type 2 diabetes is a growing health issue due to its increased prevalence and lack of an ideal therapy [1]. Epidemiological studies have demonstrated that hypertriglyceridemia is an important risk factor associated with insulin resistance and β-cell dysfunction [3, 4]. Lipoprotein lipase (LPL) gene knockout heterozygous mice, an animal model of genetic hypertriglyceridemia, exhibited significant insulin resistance, compensatory increased insulin secretion, and impaired glucose tolerance [5]. It might be possible to prevent the development of type 2 diabetes mediated through alleviating insulin resistance and β-cell dysfunction by controlling hypertriglyceridemia. Many studies have shown some beneficial effects of fenofibrate on glucose metabolism in patients with prediabetes, type 2 diabetes, or metabolic syndrome [10, 11]. There is lack of clinical evidence supporting the effects of lowering TG for insulin sensitivity and β-cell function in hypertriglyceridemia patients with

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