Effect of ciprofibrate on lipoprotein metabolism and oxidative stress parameters in patients with type 2 diabetes mellitus and atherogenic lipoprotein phenotype

Abstract

The effect of ciprofibrate therapy on plasma lipids and lipoproteins, HDL and LDL subfraction profile, fractional esterification rate of HDL cholesterol (FER(HDL)) and the resistance of LDL and serum lipids to oxidation was studied in 24 males with type 2 diabetes and atherogenic lipoprotein phenotype (ALP). We also examined the effect of ciprofibrate therapy on oxidative DNA damage in peripheral lymphocytes. No differences in glucose, HbA1C and BMI levels were found after three months of ciprofibrate therapy. Ciprofibrate significantly decreased total cholesterol and triglyceride levels by 5.5% and 50% (p = 0.05; 0.001, respectively) and increased HDL-cholesterol levels by 8.5% (p = 0.05). FER(HDL) and LDL subfraction profile were also favorably affected. However, no effect on HDL subclasses was found. There were no statistically significant differences in lipid resistance to oxidation measured in serum and in LDL (lag time and Vmax) before and after therapy. No significant effect of ciprofibrate was found on oxidative DNA damage. The evaluation of the relationship between oxidative damage of purines with lag time in LDL and maximal rate of serum lipid oxidation showed significant correlations after therapy (r = -0.58; 0.47, p = 0.01; 0.05, respectively), but only trends before starting ciprofibrate treatment. Type 2 diabetes mellitus represents a complex metabolic disorder expressed in glucose and lipoprotein disturbances and increased oxidative stress. Ciprofibrate therapy favorably affected major features of lipid abnormalities of diabetic patients, but the level of oxidative stress assessed by in vitro and in vivo methods was not changed. The evaluation of expected logical correlations between the parameters of lipoprotein metabolism, lipid resistance in serum and LDL, and oxidative DNA damage showed that those correlations were more relevant and significant after ciprofibrate treatment and were not related with glucose homeostasis.

The clinical significance of the size of low-density-lipoproteins and the modulation of subclasses by fibrates

“…Raslova et al 58 tested the effects of ciprofibrate (100 mg/daily for 12 weeks) in 24 male patients with type 2 diabetes, showing a beneficial effect on LDL size (from 223 to 232 angstrom, p < 0.05). More recently Guerin et al 59 studied the effects of ciprofibrate (100 mg/day for 6 weeks) on LDL subclasses in patients with combined or mixed hyperlipidaemia.…”

“…All fibrates (e.g., gemfibrozil, bezafibrate, fenofibrate and ciprofibrate) were used in patients with a very wide range of lipid alterations and with a predominance of all LDL subclasses; larger, intermediate or smaller particles. Many studies also considered higher-risk populations, including those with coronary atherosclerosis 24,34,57 , type 2 diabetes 16,21,22,36,39,40,42,43,47,58 , metabolic syndrome 48,53,55 and renal disease 41 .…”

Antidiabetic Action of Bezafibrate in a Large Observational Database

“…Studies of the other fibrates (gemfibrozil, fenofibrate, ciprofibrate, and clofibrate) have not shown such effects (8–14), and these drugs are far more selective for PPAR-α than bezafibrate (15). Hence, it is reasonable to hypothesize that the status of bezafibrate as a pan-PPAR agonist may give it antidiabetic properties unique among fibrates.…”

The critical issue linking lipids and inflammation: Clinical utility of stopping oxidative stress

“…Fibrates decrease the progression of atherosclerosis and reduce CV risk (198). However, the evidence does not support that fibrates reduce OS beyond what would be expected from lowering TG (199). Numerous studies confirm that proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors significantly lower TG and CV risk (200)(201)(202).…”