Effect of Candesartan to Plasma MMPs and TIMPs in Hypertensive Type 2 Diabetic Patients

Backgrounds: Candesartan, an angiotensin Ⅱ receptor antagonist has been reported to have an antiproteinuric effect and increase insulin sensitivity with diabetic nephropathy. The aim of this study was to test whether candesartan affects proteinuria, insulin sensitivity, and serum MMP (matrix metalloproteinase)-2, MMP-9, TIMP (tissue inhibitor of metalloproteinase)-1, and TIMP-2. Method: Total of 111 patients were enrolled in this study: 29 patients who have type 2 diabetes with an albumin excretion rate of over 30 mg/day, 33 patients who have type 2 diabetes with an albumin excretion rate of 30 mg/day or less and 49 healthy controls. 62 patients with type 2 diabetes took 8-16 mg/day of candesarta for 12 weeks and the following parameters were determined: weight, height, diastolic blood pressure (DBP), systolic blood pressure (SBP), duration of diabetes, age, biochemical parameters, MMP-2, MMP-9, TIMP-1, and TIMP-2 levels. Results: There was no significant difference in BMI, DBP, SBP, duration of diabetes, age, biochemical parameters except for albumin excretion rate between diabetic patients with and without nephropathy. The serum concentrations of MMP-2, MMP-9, TIMP-1 and TIMP-2 increased after the treatment in both diabetic patients. Insulin sensitivity also increased after candesartan treatment. Conclusions: Candesartan administration for 12 weeks was effective in decreasing hypertension, decreasing insulin resistance and serum concentrations of MMP-2, MMP-9, TIMP-1 and TIMP-2 for both patients with diabetes and diabetic nephropathy.ope