Effects of rosiglitazone on serum paraoxonase activity and metabolic parameters in patients with type 2 diabetes mellitus

Abstract

Human serum paraoxonase contributes to the anti-atherogenic effect of high-density lipoprotein cholesterol (HDL-C) and has been shown to protect both low-density lipoprotein cholesterol (LDL-C) and HDL-C against lipid peroxidation. We investigated the effects of rosiglitazone on paraoxonase activity and metabolic parameters in patients with type 2 diabetes mellitus [50 patients (30 males, 20 females); mean±SD age: 58.7±9.2 years, body mass index: 28.2±4.1'kg/m2], in whom glucose control could not be achieved despite treatment with metformin, sulphonylurea, and/or insulin. The patients were given 4'mg/day rosiglitazone for 3 months in addition to their usual treatment. Serum paraoxonase activity, malondialdehyde, homocysteine, and lipid profile were measured at the time of initiation and at the end of therapy with rosiglitazone. After rosiglitazone therapy, serum levels of HDL-C, apolipoprotein A-1, and paraoxonase activity increased significantly (P<0.05) and malondialdehyde, homocysteine, lipoprotein(a), and glucose levels decreased significantly (P<0.05), but no significant changes in levels of total cholesterol and apolipoprotein B were observed. Triglyceride levels also increased significantly (P<0.05). Rosiglitazone treatment led to an improvement in glycemic control and to an increase in paraoxonase activity and HDL-C levels. Although rosiglitazone showed favorable effects on oxidant/antioxidant balance and lipid profile, further studies are needed to determine the effect of rosiglitazone on cardiovascular risk factors and cardiovascular morbidity and mortality.

Current Advances in the Biochemical and Physiological Aspects of the Treatment of Type 2 Diabetes Mellitus with Thiazolidinediones

“…PPAR γ is highly expressed in the vascular system, where it is involved in the repression or expression of certain genes such as angiotensin type 1 receptor (AT1R), which can prevent or ameliorate endothelial dysfunction and atherosclerosis [ 3 , 15 , 16 , 60 , 67 , 73 , 74 ]. In accordance with this, it has been seen that, in animal models, repression of the expression of PPAR γ promotes cardiomyopathy, lipid deposition, arrhythmias, hypertrophy, and increased expression of cardiac inflammatory markers [ 61 , 66 , 70 , 71 ].…”

Thiazolidinediones Cause Cardiotoxicity via PPARγ- Independent Mechanism

“…Rosiglitazone increased low-density lipoprotein cholesterol (LDL-C) concentration of 18.6% among T2DM patients treated for 26 weeks with an 8-mg daily dose via increasing serum paraoxonase activity, which protects LDL-C against lipid peroxidation. This TZD also significantly increased triglyceride levels in 50 patients who were given at 4 mg/day for 3 months in addition to their usual treatment compared to baseline levels [86,87]. Higher LDL-C level was consistently and independently associated with higher incidences of major adverse cardiovascular events after controlling for conventional risk factors [88].…”

Correlation Between Serum PON1 Arylesterase Activity and Rs 854573 &lt;i&gt;PON1 A &lt; G&lt;/i&gt; Polymorphism with Type 2 Diabetes in an Eastern Indian Cohort

“…Several studies are being conducted using a no of different antioxidative drugs such as simvastatin, rosiglitazone, in T2DM therapy. Simvastatin treatment shows no effects on PON1 activity modulation in Q192R and M55LPON1 polymorphisms [72] but rosiglitazone showed favorable effects on improvement in glycemic control and to an increase in paraoxonase activity and HDL-C levels [73]. Although the present study is devoid of any therapeutic management, the excessively low levels of PON1 AREase activity give some lights into pharmacogenomic aspect of the study implying the need to either rosiglitazone like drug treatment in patients or need of thorough care in patient groups using a combination of drug therapies.…”