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The effects of PPARα and PPARγ agonists on proteinuria and oxidative stress in patients with type 2 diabetes mellitus

Zafer Ufuk Cinkara, Saime Paydas, Mustafa Balal, Ertan Kara,

Objectives: In diabetes mellitus, renal-cardiovascular complications are important public health problems. We aimed to evaluate the effect of pioglitazone and fenofibrate, as PPAR agonists, on proteinuria and oxidative stress in diabetic patients.

Patients and Methods: 60 type 2 diabetic patients were included in this study. 15 patients with HbA1c<7 and triglyceride<350 mg/dl comprised GA. Pioglitazone was added to the therapy in 15 patients with HbA1c>7 and triglyceride<350 mg/dl (GB). In GC, patients with triglyceride>350 mg/dl and HbA1c<7, fenofibrate was added to their therapy. Pioglitazone and fenofibrate were added to the therapy for 15 patients with HbA1c>7 and triglyceride>350 mg/dl (GD). Biochemical tests, serum total oxidative status, paraoxonase-1 enzyme activity, C-reactive protein (CRP), brain natriuretic peptide (BNP), and spot urine protein/creatinine were measured at baseline (1), the 6th week (2) and the 12th week (3). The glomerular filtration rate (GFR) was also calculated.

Results: In GB and GD, glucose (1) and HbA1c (1) were higher than glucose (2,3) and HbA1c (2,3) (p<0.05 for all). In GC and GD, triglycerides (1) were higher than triglycerides (2,3) (p<0.05 for all). Proteinuria, blood pressure, GFR, BNP, CRP, total oxidant status and paraoxonase-1 enzyme activity were not changed with pioglitazone and/or fenofibrate treatment.

Conclusion: In contrast to blood glucose/triglyceride levels, pioglitazone and fenofibrate alone or in combination did not alter proteinuria, BNP, GFR, CRP, TOS or PON-1 enzyme activity during a period of 12 weeks in diabetic patients with different glucose or triglyceride levels. This could be related to the short study period and limited patient number.