Effect of pioglitazone and rosiglitazone on mediators of endothelial dysfunction, markers of angiogenesis and inflammatory cytokines in type-2 diabetes

Abstract

The purpose of this study was to assess the effects of PPAR-gamma agonists (pioglitazone and rosiglitazone) on mediators of endothelial dysfunction and markers of angiogenesis in patients with type-2 diabetes. Pioglitazone group showed favorable reductions in serum total cholesterol, triglycerides, LDL cholesterol, VLDL cholesterol and increase in HDL cholesterol as compared to rosiglitazone group, after 16 weeks of treatment and also with control group. There was significant reduction of CRP level in pioglitazone and rosiglitazone group. The level of serum TNF-alpha decreased significantly in pioglitazone and mildly decreased in rosiglitazone group. The level of VEGF, IL-8 and Angiogenin were increased in pioglitazone than rosiglitazone group. There were no significant changes observed in the serum angiogenin and IL-8 levels in the control group. Pioglitazone and rosiglitazone therapy in type-2 diabetes subjects have additional benefits of reducing mediators of endothelial dysfunction. Increase in angiogenesis markers in patients receiving pioglitazone could have variable effects in diabetic nephropathy and retinopathy as there may be increased vascular neogenesis. Pioglitazone has advantage over rosiglitazone in lowering lipid and proinflammatory cytokines.

Fat redistribution preferentially reflects the anti-inflammatory benefits of pioglitazone treatment

“…Recently, CRP was reported to be independently associated with short-term mortality risk in type 2 diabetes mellitus patients [19]; and several studies have shown that pioglitazone reduces plasma CRP levels [3][4][5][6][7][8][9][10][11][12][13]. Moreover, 16 weeks of pioglitazone treatment decreased CRP levels by 42% in type 2 diabetes mellitus patients [12]; and pioglitazone further reduced CRP in patients with hypertension and diabetes who were receiving angiotensin II receptor blockers [5]. In a 6-month randomized double blind study, pioglitazone in combination with insulin treatment was shown to decrease hsCRP levels more than did insulin monotherapy alone [9].…”

“…reduction of proinflammatory markers including C-reactive protein (CRP) [3][4][5][6][7][8][9][10][11][12][13]. C-reactive protein is an acute-phase reactant that is known as a proinflammatory marker and a predictor of cardiovascular events [14][15][16].…”

Peroxisome proliferator-activated receptors as stimulants of angiogenesis in cardiovascular disease and diabetes

“…Pioglitazone treatment has been shown to increase serum VEGF, IL-8, and angiogenin levels in patients with type 2 diabetes. 51 In another study thiozolidinedione use in patients with type 2 diabetes was associated with diabetic macular edema.…”

Design, history and results of the Thiazolidinedione Intervention with vitamin D Evaluation (TIDE) randomised controlled trial

“…They also reduce many other cardiovascular risk factors including: incident diabetes [2,3]; insulin resistance [4,5]; blood pressure [6]; albuminuria [7]; renal disease [8,9]; inflammatory markers [10]; revascularisation after percutaneous coronary intervention [11]; and carotid [3,[12][13][14] and coronary atherosclerosis [15,16]. These observations and analyses of data from administrative databases in 2005 show that people prescribed TZDs may have fewer cardiovascular events or deaths than people prescribed other agents [17,18] and suggest that TZDs may improve cardiovascular outcomes.…”