Effect of rosiglitazone on plasma adiponectin levels and arterial stiffness in subjects with prediabetes or non-diabetic metabolic syndrome

Abstract

Objective: Thiazolidinediones have favorable influences on surrogate markers of atherosclerosis such as adiponectin, and arterial stiffness in diabetic patients. However, it is not well known whether these beneficial effects occur in subjects without diabetes, such as prediabetes or the non-diabetic metabolic syndrome (MetS). The present study was therefore designed to evaluate the effectiveness of the insulin-sensitizing agent rosiglitazone on circulating adipocytokine levels and brachial-ankle pulse wave velocity (baPWV) in non-diabetics. Design and methods: Ninety-nine subjects with prediabetes or non-diabetic MetS were randomly assigned to either rosiglitazone or an untreated control group (50 and 49 subjects respectively). The rosiglitazone group was treated daily for 12 weeks with 4 mg rosiglitazone. All subjects received a 75 g oral glucose test (OGTT) before and after treatment. In addition, baPWV, together with the levels of adiponectin, resistin, and high sensitivity C-reactive protein (hsCRP) were determined. Results: Rosiglitazone treatment significantly increased circulating adiponectin levels (P , 0.001) relative to the control group (P ¼ 0.21). Plasma resistin levels were unchanged in both the rosiglitazone-treated and -untreated groups, but baPWV and hsCRP were significantly decreased (P , 0.001 and P ¼ 0.003 respectively) in the rosiglitazone group only. Multiple linear regression analysis showed that changes in plasma adiponectin and baPWV were significantly affected by rosiglitazone treatment. Conclusions: These data suggest that rosiglitazone may have an anti-atherogenic effect in subjects with prediabetes or non-diabetic MetS.

Pharmacogenomic, Physiological, and Biochemical Investigations on Safety and Efficacy Biomarkers Associated with the Peroxisome Proliferator-Activated Receptor-γ Activator Rosiglitazone in Rodents: A Translational Medicine Investigation

“…5). Adiponectin response to RGZ in our study conforms with preclinical (Sharabi et al, 2007) and clinical observations, showing a 2.4-to 2.6-fold increase in both nondiabetic and diabetic patients (Kim et al, 2006;Pfü tzner et al, 2008), suggesting relevant PPAR-␥ stimulation. In addition, the up-regulation of PPAR-␥ mRNA adds further support for RGZ engagement with its target (Sommer and Wolf, 2007).…”

“…Vehicle [aqueous solution containing 2% Tween 80 (w/v) and 0.5% methylcellulose (w/v)], 3 mg/kg RGZ, or 45 mg/kg RGZ was administered by oral gavage daily for 4 weeks in HF rats, in parallel with vehicle; the 45-mg/kg oral dose of RGZ was administered in studies on ZDF rats. The lower dose of 3 mg/kg RGZ was selected as a clinically relevant dose for efficacy in rats (Yue et al, 2001;Kim et al, 2006;Sharabi et al, 2007;Pfü tzner et al, 2008), and the higher dose of 45 mg/kg represented the supraclinical RGZ exposure aimed to addressed the cardiorenal liability in these models.…”

Plasma resistin levels correlate with determinants of the metabolic syndrome

“…Alternatively, as metabolic syndrome by itself is associated with inflammation, there might be the possibility that resistin is rather associated with inflammation markers that would appear at different stages of metabolic syndrome development, and its correlation with other metabolic and anthropometric parameters like glucose, blood lipids, and BMI is just a secondary effect. Indeed, pharmacological approaches with TZD reduce resistin levels (44,45), although not all reports are consistent with these findings (46).…”

The relationship between nephropathy, retinopathy, obesity and arterial stiffness in type 2 diabetes mellitus

“…In our study, a statistically meaningful distinction wasn't seen in terms of PWV and Alx values between, the patient groups who were divided into groups according to their diet, exercise, oral antidiabetic and insulin treatments. In a study by Kim et al [25] it was shown that rosiglitazone decreases PWV by increasing the insulin sensitivity. In another study it was shown that insulin treatment increases PWV [26] possibly due to increased anabolic effects of insulin.…”