Rosiglitazone Reduces Insulin Requirement and C-Reactive Protein Levels in Type 2 Diabetic Patients Receiving Peritoneal Dialysis

Abstract

Glycemic control is important in determining the outcome of patients with diabetes on dialysis therapy. However, the choice of oral hypoglycemia agent is limited in these patients. Very often, a high dose of insulin is required because of the uremia-associated insulin-resistant state. Rosiglitazone (RSG), a thiazolidinedione, can improve insulin resistance, and its excretion does not rely on renal function. Moreover, it has an anti-inflammatory effect that might be beneficial in patients with renal failure. An open-label randomized study was performed in which 52 patients with type 2 diabetes on peritoneal dialysis therapy administered a constant dosage of subcutaneous insulin with stable glycemic control were randomly assigned to the administration of either RSG (fixed dose, 4 mg) plus insulin or insulin alone. Insulin was titrated to maintain hemoglobin A1c (HbA1c) and blood glucose at pretreatment levels. Study duration was 24 weeks. Both groups had similar baseline demographic characteristics, HbA1c and glucose levels, insulin requirement, and C-reactive protein (CRP) levels. Insulin requirement was decreased significantly in the RSG group (27.88 +/- 17.6 to 22.4 +/- 15.21 U/d; P < 0.001). There was a significantly greater decrease in insulin dosage in the RSG than control group (-21.5% versus +0.5%; P = 0.03), whereas glycemic control was similar between groups. At the end of the study, the RSG group also had significantly lower CRP levels than the control group (2.21 versus 8.59 mg/L; P = 0.03). No significant increase in such adverse effects as hypoglycemia, liver impairment, and fluid overload was observed in the RSG group. However, the RSG group was associated with more weight gain. Multivariate regression analysis (using decrease in HbA1c and lipid levels, change in insulin dosage, and treatment with RSG, with lipid-lowering agents) showed that only treatment with RSG was an independent predictor for posttreatment CRP level (P = 0.016). RSG in combination with insulin is well tolerated and beneficial in the treatment of patients with type 2 diabetes on peritoneal dialysis therapy by improving insulin sensitivity and decreasing inflammatory response.