Hydrochloride pioglitazone decreases urinary cytokines excretion in type 2 diabetes

Abstract

Objective: To observe the effects of hydrochloride pioglitazone on urinary cytokine excretion in type 2 diabetes and to explore its possible reno-protective mechanisms.

Design: Subjects and Methods. Ninety-eight patients with type 2 diabetes and a fasting blood glucose (FBG) levels between 7.0 and 13.0 mm and glycated haemoglobin A1c (HbA1c) ≥ 7.0% were assigned randomly to receive either the pioglitazone (DP group) or a sulphonylurea (DS group). Another 49 healthy individuals were chosen as normal controls (group NC). At the start of the study and after 12 weeks of treatment, urinary cytokines including monocyte chemoattractant protein-1 (MCP-1), transforming growth factor-β1 (TGF-β1) and vascular endothelial growth factor were measured and were expressed as a ratio of urinary creatinine excretion. Urinary albumin/creatinine ratio, FBG and HbA1c were determined at the same time.

Results: The excretion of each urinary cytokine, corrected for urinary creatinine, was significantly increased in both groups of patients with diabetes, compared with normal controls, and after a 12-week treatment were significantly decreased by both therapies but the effect of pioglitazone was statistically greater than with sulphonylureas. Urinary albumin/UCr and both systolic and diastolic blood pressure were decreased significantly by pioglitazone (P < 0.01 or P < 0.05) but not by sulphonylurea treatment (P < 0.05), while there was no significant difference in FBG or HbA1c between two groups. There was a positive correlation between the excretion of cytokines and urinary albumin /UCr (all P < 0.01).

Conclusions: This study indicates that pioglitazone reduces urinary albumin excretion by a mechanism that is at least partly independent of blood sugar control. The correlation of urinary albumin excretion with improvement in urinary cytokines suggests that this reno-protective effect of piogliazone in diabetes may be related to local reduction in cytokine activity within the kidney.