Effects of Pioglitazone on Asymmetric Dimethylarginine and Components of the Metabolic Syndrome in Nondiabetic Patients (EPICAMP Study): A Double-Blind, Randomized Clinical Trial
The present trial aimed to investigate the effects of pioglitazone on the serum level of asymmetric dimethylarginine (ADMA), a marker of endothelial function, and some indices of inflammation and glucose and lipid metabolism in nondiabetic metabolic syndrome patients. 104 eligible participants (57% female; age between 20 and 70) were enrolled in a double-blind placebo-controlled trial and were randomized to receive either pioglitazone (uptitrated to 30？mg/day) or matching placebo for 24？weeks. Participants were clinically examined and a blood sample was obtained at baseline and at the end of the trial. Pioglitazone significantly improved C-reactive protein level irrespective of changes in insulin sensitivity. Compared with the placebo group, alanine and aspartate transaminases were decreased and high-density lipoprotein cholesterol was increased after treatment with pioglitazone. A considerably greater weight gain was also recorded in the intervention group. We failed to observe any significant changes in serum ADMA in either group and between groups with and without adjustment for age, sex, and components of the metabolic syndrome. In a nutshell, pioglitazone seems to have positive effects on lipid profile, liver transaminases, and systemic inflammation. However, its previously demonstrated endothelial function-improving properties do not seem to be mediated by ADMA. 1. Introduction Metabolic syndrome (MetS) is widely accepted as a concept which encompasses a cluster of cardiovascular risk factors. Although some authors have claimed against the additional value of the syndrome over its component parts in identifying cardiometabolic risk [1], it has been demonstrated that affected individuals are at two-to-three-fold higher risk of developing coronary heart disease and a fivefold increased risk of type-2 diabetes mellitus (T2DM) [2, 3]. Insulin resistance (IR), a key contributing mechanism to the development of the syndrome, is turned out to be associated with endothelial dysfunction (ED) [4]. In turn, ED is correlated with all risk factors of atherosclerosis [5]. ED is generally defined as the impairment of endothelium-dependent vasodilatation secondary to reduced bioavailability of nitric oxide (NO) [6]. NO production is catalyzed by the nitric oxide synthase (NOS) family of enzymes [7]. It has been shown that insulin induces endothelium-dependent vasodilatation via activating endothelial NOS [8]. Decreased bioavailability of NO mediated by endogenous inhibitors of NOS would diminish delivery of insulin and glucose to metabolically active tissues and,
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