The effects of PPAR α ve PPAR γ agonists on renal functions, proteinuria, oxidative stress, blood pressure, plasma glukoz level and HbA1c in patients with Type 2 Diabetes mellitus

Objectives: Nowadays, Type 2 diabetes mellitus (DM) disease is a rapidly growing public health problem. In long term, micro and macro vascular complications affect the morbidity and mortality of patients with diabetes mellitus. In this study, pioglitazone and fenofibrate, which are acting on PPARs family, were added to the therapy of patients and evaluated the effects on renal functions, plasma glucose levels, HbA1c, proteinuria, blood pressure and oxidative stress. Material and Methods: Sixty diabetic patients who were followed up by Endocrinology and Nephrology out patient clinic in Cukurova University Medical Faculty, were included. Patients were divided into 4 groups which were A, B, C and D. In each group there were 15 patients. Group A was consisting of 15 diabetic patients with well controlled glycemia and lipidemia. Group B was containing 15 type 2 DM patients whose HbA1c>7 without hyperlipidemia. For hyperglycemia pioglitazone was added to their theapy. In Group C patients had triglyceride levels higher than 350 and well controlled glycemia. Group C patients were treatec with fenofibratese. Fifteen patients with HbA1c>7 and triglyceride levels higher than 350, were consisted group D. Pioglitazone and fenofibrate were given to these patients. These medications were started on patients for requirement of their clinical conditions and unless any contraindication. The complete blood counts, fasting blood glucose, HbA1c, BUN, Creatinine, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, CRP, AST, ALT, total protein, albumin, total bilirubin, ALP, Creatin Kinase, Brain natriuretic peptid (BNP), in spot urine the ratio of protein to creatinine were measured at initial admission, 6th weeks and 12th weeks. Glomerular filtration rate (GFR) values were calculated with Cockcroft- Gault, MDRD, CKD-EPI formulas. Blood samples as 4-5 mL were centrifuged and stored in -80 0C for measure of total oxidative status and PON-1 enzyme activity: Findings: In groups B and D according to baseline values (1), glucose and HbA1C decreased statistically significantly on 6. Weeks (2) and 12. Weeks (3) (p<0.05 for all). Also comparing baseline levels (1) triglyceride levels were decreased on 6th week (2) and 12th week (3) in groups C and D (p<0.05 for all). There were no statistically significant positive/ negative effects of the drugs on proteinuria, blood pressure, renal function, BNP, CRP, total oxidant status and PON-1 enzyme activity. Results: Pioglitazone were found to be effective in achieving glycemic control in patients with type 2 DM. Fenofibrate was found to provide effective for reduction of triglycerides in type 2 DM patients with hypertriglyceridemia. The administration of these drugs alone or in combination were not found to be negative or positive effects on proteinuria, blood pressure, renal function, BNP, CRP and total oxidant status and paraoxonase-1 enzyme activity. Key Words: Type 2 diabetes mellitus, oxidative stress, pioglitazone, fenofibrate.