Increased plasma dipeptidyl peptidase 4 activities predict new-onset microalbuminuria in association with its proinflammatory effects in Chinese without diabetes: a four-year prospective study

Abstract

Background: Recent evidence supports a protective role of dipeptidyl peptidase 4 (DPP4) inhibitors in lowering microalbuminuria (MAU) in diabetes but till now few studies have investigated the associations between DPP4 activity and MAU in nondiabetic Chinese individuals. This study tested whether DPP4 activity could predict new-onset MAU in Chinese without diabetes.

Methods: This was a 4-year prospective study conducted in Sichuan, China. A total of 664 Chinese women and men aged 18-70 years were studied. Circulating DPP4 activity, inflammatory markers and urinary albumin-to-creatinine ratio (ACR) were measured at baseline and 4 years later.

Results: The incidence of MAU during follow-up was 33.1 per 1000 patient-years. At baseline, individuals in the highest quartile of DPP4 activity had higher age, body mass index, waist/hip ratio, systolic blood pressure, diastolic blood pressure, fasting insulin, low-density lipoprotein-cholesterol, interleukin-6, high-sensitivity C-reactive protein, urinary albumin-to-creatinine ratio and lower high-density lipoprotein-cholesterol compared with individuals in the lowest quartile. After a 4-year follow-up, 88 individuals developed MAU. In multiple linear regression analysis, baseline DPP4 activity was an independent predictor of an increase in inflammatory markers and ACR over a 4-year period (all P < 0.05). In multivariable-adjusted models, the odds ratio for incident MAU comparing the highest with the lowest quartiles of DPP4 activity was 3.48 (95% CI: 1.50-8.09) after adjustment for confounding risk factors (P < 0.01). The incidence of MAU owing to DPP4 activity increased by 18.59%.

Conclusion: DPP4 activity is an important predictor of the onset of inflammation and MAU in Chinese apparently without diabetes. This finding may have important implications for understanding the proinflammatory role of DPP-4 in the pathogenesis of MAU.

Trial registration number: #TR-CCH-Chi CTR-CCH-00000361.

Keywords: ACR; DPP4 activity; inflammation; microalbuminuria.