OBJECTIVE To compare extra-lipid effects of statins and fibrates in relation to the baseline metabolic status of patients. launch. These abnormalities were alleviated by both atorvastatin and fenofibrate treatment. CRP-lowering and monocyte-suppressing BMS-707035 actions were more pronounced for atorvastatin in subjects with impaired fasting glucose and for fenofibrate BMS-707035 in individuals with impaired glucose tolerance. CONCLUSIONS The presence of pre-diabetes potentiates metabolic syndrome-induced abnormalities in plasma markers CLG4B of swelling and hemostasis and in monocyte secretory function. Both atorvastatin and fenofibrate show BMS-707035 multidirectional pleiotropic effects in subjects with metabolic syndrome the strength of which seem to be partially determined by the type of pre-diabetes. The anti-inflammatory endothelial-protective antioxidant and anti-thrombotic actions of statins and fibrates are observed not only in BMS-707035 individuals with dyslipidemia (1-5) but also in subjects with early and late glucose rate of metabolism abnormalities (6-8). This suggests that metabolic syndrome (MS) individuals may receive more benefits from statin or fibrate treatment than individuals suffering from isolated lipid or glucose metabolism disturbances. No previous study has examined whether the presence and type of pre-diabetes determines cardiovascular risk element concentrations and the extra-lipid effects of lipid-lowering providers in MS individuals. Study DESIGN AND METHODS The study included 242 individuals with recently diagnosed and previously untreated MS. MS was diagnosed using National Cholesterol Education System Adult Treatment Panel III criteria. The exclusion criteria and power calculations are explained in the online appendix (available at http://care.diabetesjournals.org/cgi/content/full/dc10-0272/DC1). The study protocol was authorized by the local ethics committee. All enrolled MS individuals were given detailed advice on how to accomplish the goals of way of life modification: a reduction in excess weight of 7% or more if necessary; total excess fat intake less than 30% of total energy intake; saturated excess fat intake less than 7% of energy consumed; cholesterol intake less than 200-mg per day; an increase in dietary fiber intake to 15-g BMS-707035 per 1 0 kcal; and moderate-to-vigorous exercise for at least 30 min per day. On the basis of fasting plasma glucose MS individuals were allocated into one of the two organizations: individuals with pre-diabetes (= 183) and individuals with normal glucose tolerance (NGT) (= 59) (online appendix). The former group was additionally divided into three subgroups: individuals with isolated fasting glucose (IFG) (= 61) individuals with isolated impaired glucose tolerance (IGT) (= 62) and individuals with concomitant IFG and IGT (IFG + IGT) (= 60). The individuals in each group were randomized inside a double-blind fashion to micronized fenofibrate (200 mg) atorvastatin (40 mg) or placebo which were given once daily for 90 days. MS individuals were compared with age- and sex-matched healthy subjects without lipid and glucose rate of metabolism abnormalities (= 48). Plasma lipid/lipoprotein profile total free fatty acids fasting and 2-h postchallenge glucose levels A1C homeostasis model assessment (HOMA) index high-sensitivity C-reactive protein (hs-CRP) fibrinogen element VII plasminogen activator inhibitor 1 (PAI-1) and monocyte production of tumor necrosis element-α interleukin (IL)-1β IL-6 and monocyte chemoattractant protein-1 were identified before and after 30 and 90 days of therapy (4 6 9 Statistical analysis was performed as previously explained (4 6 RESULTS Apart from disturbances in lipid profile and glucose metabolism markers the presence of MS was associated with higher plasma levels/activity of hs-CRP fibrinogen element VII and PAI-1 and improved monocyte launch of tumor necrosis element-α IL-1β IL-6 and monocyte chemoattractant protein-1 (online appendix Table 1). No severe adverse effects were observed throughout the study and 234 individuals completed the study (on-line appendix). Table 1 Atorvastatin and fenofibrate effects on lipid/lipoprotein profile glucose metabolism low-grade swelling hemostasis and cytokine secretion by stimulated monocytes in MS individuals coexisting with pre-diabetes or NGT In pre-diabetic individuals only fenofibrate decreased fasting and postchallenge plasma glucose HOMA index and A1C (Table 1). In MS individuals with NGT or pre-diabetes atorvastatin and fenofibrate improved lipid/lipoprotein.