PPARαAgonist Fenofibrate Reduced the Secreting Load ofβ-Cells in Hypertriglyceridemia Patients with Normal Glucose Tolerance

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.

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

“…Importantly, fenofibrate treatment administered to the IGT patients with hypertriglyceridemia for 12 weeks resulted in the significant decrease in FINS, HOMA2-%B, and HOMA2-IR and the significant increase in HOMA2-%S and McA; the change in TG was inversely related to the change in McA. Our findings are similar to the previous studies in hypertriglyceridemic patients with prediabetes [12] or with NGT [13]. However, our findings are in contrast to some recent studies in nondiabetic individuals with insulin resistance [14] or in subjects with T2DM [15, 16].…”

“…Most studies have indicated the insulin-sensitizing actions of fenofibrate, although the actions have been questioned by other studies. Some studies have demonstrated that fenofibrate exerted protective effects on hypertriglyceridemic patients with prediabetes [12], and ameliorated insulin resistance in hypertriglyceridemic patients with normal glucose tolerance (NGT) [13]. On the contrary, other studies have found that fenofibrate has no effects on the insulin sensitivity in insulin-resistant nondiabetic subjects [14] or in subjects with T2DM [15, 16].…”

Crosstalk of Hyperglycemia and Dyslipidemia in Diabetic Kidney Disease

“…It has been demonstrated in multiple animal studies that fenofibrate reduces albuminuria in patients with diabetes [25,61,87] . In addition to reducing albuminuria, fenofibrate has been reported to ameliorate hyperglycemia [88,89] . Acute fibrate-induced creatinine elevation in T2D with relatively preserved renal function may confer longer-term renoprotective effects.…”

Fenofibrate decreased microalbuminuria in the type 2 diabetes patients with hypertriglyceridemia

“…Several studies have shown that peroxisome proliferator-activated receptor α (PPARα) agonist could inhibit renal inflammation and fibrosis and prevent renal oxidative stress [11][12]. Our previous studies have shown that fenofibrate therapy can significantly reduce insulin resistance and the secretory load of β cells [2]. Fenofibrate could improve plasma levels of tetrahydrobiopterin (BH4) by increasing the guanosine 5-triphosphate cyclohydrolase-I expression and protect endothelial function [3][4].…”