High triglycerides and low HDL cholesterol are frequently associated with insulin resistance. Statins are potent hypocholesterolemic drugs, while fibrates are better at reducing triglycerides and enhancing HDL. However, little is known of their effects on other parameters potentially associated with insulin resistance, such as γ-glutamyl transferase (GGT) (1) and apolipoprotein CIII (2).

In this cross-sectional study, we have analyzed the biochemical profiles of 500 men from Southwestern France as a function of their hypolipidemic therapy. Comparison between untreated (n = 361) and fibrate (n = 50)- and statin (n = 89)-treated subjects revealed no difference in their levels of total, LDL, and HDL cholesterol, apo B, apo AI, and apo E, after adjustment for age, BMI, alcohol intake, smoking, and physical activity. This suggests that both therapies are equally effective at normalizing classic lipid variables.

By contrast, apo CIII was higher in the statin group (34.3 ± 13.9 mg/l) than in both the fibrate (26.7 ± 10.3, P < 0.01) and nontreated (28.7 ± 10.9 mg/l, P < 0.001) groups after adjustment for confounders, including triglycerides. Similar differences were found for Lp B:CIII, a marker measuring apo CIII associated with apo B. These observations might indicate an additional beneficial effect of fibrates, considering that Lp B:CIII has been described as an independent predictor of coronary events, better than triglycerides (3).

Most interesting, GGT was two times lower for fibrates (36.7 ± 24.4 units/l) than for the two other groups (67.1 ± 71.3 units/l for statins, P < 0.01 and 58.1 ± 51.7 units/l in nontreated subjects, P < 0.01), taking into consideration potential confounders, including alcohol intake and triglycerides. GGT is often elevated in obese subjects and has been associated with steatosis, which could be due to increased effects of insulin in the liver and could contribute to the development of systemic insulin resistance and hyperinsulinemia in obesity. GGT was reported as one of the independent predictors of the metabolic syndrome and type 2 diabetes (1,4). Moreover, GGT was detected in atheromatous plaques and has been shown to promote LDL oxidation by hydrolyzing glutathione into more potent iron reductants (5). Thus, fibrates may prove effective in the treatment of dyslipidemic diabetic or obese patients, since they should improve the hepatic suffering induced by the triglyceride load and also limit the potential proatherogenic effects of GGT.

This study was supported by Laboratoires Fournier.

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Address correspondence to Prof. Jean Ferrières, Inserm U558, Faculté de Médecine, 37 allées Jules Guesde, 31 073, Toulouse Cedex 03, France. E-mail: [email protected].

DIABETES CARE
2003