Abstract

Background: Glomerular endothelial injury is commonly encountered in diabetic nephropathy, as in type 2 diabetes mellitus (T2DM). Microalbuminuria is associated with endothelial cell dysfunction, and is a significant risk factor for cardiovascular mortality in diabetes. This study was undertaken to study the effect of sitagliptin, a dipeptidyl peptidase-4 (DPP4) inhibitor, on microalbuminuria as a mechanism of improving glomerular endothelial injury in patients with T2DM.
Methods: Sitagliptin, a DPP4 inhibitor, was administered to twenty patients with T2DM, 50 mg/day, for 8 weeks. Plasma levels of glucose, HbA1c, stromal-cell-derived factor-1 alpha (SDF1α), thrombomodulin (TM), serum creatinine, and urinary albumin/creatinine ratio (ACR) were measured at the start and the end of the study. The alteration patterns were statistically compared and analyzed together with their pathologic states. Another nineteen control patients were enrolled in this study.
Results: Sitagliptin treatment resulted in 14% decrease (P=0.0003 vs. control) in HbA1c from 7.2±1.2 to 6.2±1.4%, 74% increase (P<0.0001 vs. control) in SDF1α from 205±70 to 355±80mmol/L, 9% decrease(P=0.0029 vs. control) in TM from 3.2±1.3 to 2.9±1.1FU/mL, 41% decrease (P=0.0095 vs. control) in ACR from 5.5±5.2 to 3.3±4.5mg/mmol. Cr after 8 weeks. Regression analysis revealed a closer relationship between SDF1α and ACR. No remarkable changes were observed in controls. As microalbuminuria represents glomerular endothelial dysfunction, these data suggest the additional effect by DPP4 inhibitor on glomerular endothelial damage.
Conclusion: DPP4 inhibitor decreased urinary albumin excretion in association with the improvement of glomerular endothelial injury in patients with T2DM.