Attenuation of Progression of Insulin Resistance in Patients With Coronary Artery Disease by Bezafibrate

Abstract

Background: Development of insulin resistance (IR) may be important in the pathogenesis of both metabolic syndrome and type 2 diabetes mellitus. Few data are available regarding the short-term efficacy of the peroxisome proliferator-activated receptor ligand bezafibrate on IR, and its long-term effect is unknown. The present analysis aimed to investigate the effect of bezafibrate on IR in patients with coronary artery disease enrolled in the Bezafibrate Infarction Prevention Study. Methods: Metabolic and inflammatory parameters were analyzed from stored frozen plasma samples obtained from patients who completed a 2-year, randomized, doubleblind, placebo-controlled study. The homeostatic indexes of IR (HOMA-IRs) were calculated according to the homeostasis model of assessment. Results: Both the patients taking bezafibrate (n = 1262) and those taking placebo (n = 1242) displayed similar base-line characteristics. The HOMA-IRs significantly correlated at baseline and during follow-up with glucose (r=0.35 and 0.31, respectively) and triglycerides (r=0.16 and 0.19, respectively). In a subgroup of 351 patients with diabetes, HOMA-IR at baseline was 88% higher than in their counterparts with normal glucose levels (PϽ.001). In the placebo group, during follow-up there was a significant 34.4% rise in HOMA-IR. In contrast, in the bezafibrate group there was only a nonsignificant 6.6% change in HOMA-IR. The intergroup differences in percentage changes of HOMA-IR were in favor of bezafibrate (PϽ.001). Conclusions: In patients with coronary artery disease enrolled in our study, as represented by the placebo group, HOMA-IR increased over time. During the 2 years of the follow-up, bezafibrate significantly attenuated this process.

Metabolomics reveal 1-palmitoyl lysophosphatidylcholine production by peroxisome proliferator-activated receptor α

“…It was infused straight into the MS system at a fl ow rate of 20 µl/min at 200 pg/µl (in 50% acetonitrile, 0.1% slows the progression of focal coronary atherosclerosis, and reduces the number of coronary events in young survivors of myocardial infarction ( 17 ). It is interesting to note that fi brates, including bezafi brate, contribute to the improvement of both dyslipidemia and glucose metabolism disorder (18)(19)(20). Although PPAR ␣ target genes are widely known, little is known about the variation of metabolites in plasma and liver during the activation of these genes.…”

“…It is interesting to note that fi brates, including bezafibrate, contribute to the improvement of not only dyslipidemia but also glucose metabolism disorder (18)(19)(20). However, the molecular basis of this effect remains unexplained.…”

Hypertriglyceridemia: a too long unfairly neglected major cardiovascular risk factor

“…Fibrates activate PPAR alpha, which binds to a PPAR alpha response element in conjunction with the retinoid X receptor. Other effects of fibrates include an increase in the size of LDL particles, increased removal of LDL, and a reduction in the levels of plasminogen activator inhibitor type I [158][159][160][161][162].…”

PPARα activation elevates blood pressure and does not correct glucocorticoid-induced insulin resistance in humans

“…Treatment with fenofibrate enhances insulin sensitivity in dyslipidemic patients with normal glucose metabolism (36) but has no effect on insulin responses in subjects with metabolic syndrome (32). Bezafibrate prevents the progression of insulin resistance in patients with coronary artery disease (28).…”