PPAR-α Agonist Fenofibrate Reduces Insulin Resistance in Impaired Glucose Tolerance Patients with Hypertriglyceridemia: A Cross-Sectional Study

Abstract

Introduction: Peroxisome proliferator-activated receptor-α (PPAR-α) agonists can regulate metabolism and protect the cardiovascular system. This study investigated the effects of PPAR-α agonist fenofibrate on insulin resistance in patients with impaired glucose tolerance (IGT). Methods: This research evaluated cross-sectional and interventional studies. 191 subjects with IGT were divided into a hypertriglyceridemia group (HTG group, n = 118) and a normal triglyceride (TG) group (NTG group, n = 73). 79 subjects with normal glucose tolerance were recruited as a control group. The HTG group was treated with fenofibrate (200 mg/day) for 12 weeks. The homeostatic model assessment index 2 (HOMA2) and the McAuley index (McA) were calculated. Results: HOMA2 for β-cell function (HOMA2-%B) was 93.47 ± 26.28, 68.47 ± 21.29, and 79.92 ± 23.15 in HTG, NTG, and control groups, respectively. HOMA2 for insulin sensitivity (HOMA2-%S) was 48.40 (39.70, 68.70), 110.20 (62.55, 141.95), and 101.20 (79.90, 140.10) in HTG, NTG, and control groups, respectively. HOMA2 for insulin resistance (HOMA2-IR) was 2.09 (1.46, 2.52), 0.92 (0.70, 1.61), and 0.99 (0.71, 1.25) in HTG, NTG, and control groups, respectively. McA was 5.05 ± 0.76, 7.99 ± 1.79, and 8.34 ± 1.55 in HTG, NTG, and control groups, respectively. The HTG group had higher HOMA2-%B and HOMA2-IR, and lower HOMA2-%S and McA than NTG and control groups (P < 0.001 for all). Fenofibrate decreased HOMA2-%B and HOMA2-IR and increased HOMA2-%S and McA in the HTG group (HOMA2-%B: from 93.47 ± 26.28 to 89.34 ± 23.53, P = 0.018; HOMA2-%S: from 48.40 (39.70, 68.70) to 56.75 (44.88, 72.53), P < 0.001; HOMA2-IR: from 2.07 (1.46, 2.52) to 1.76 (1.38, 2.30), P < 0.001; McA: from 5.05 ± 0.76 to 9.34 ± 0.88, P < 0.001). Conclusion: PPAR-α agonists improve parameters of glucoregulation in IGT patients with hypertriglyceridemia.