Pentosidine levels in nonproteinuric diabetes associated with both low estimated glomerular filtration rate and cataract

Abstract

Background

The main objective of this study was to investigate whether plasma pentosidine levels were associated with cataract and low estimated glomerular filtration rate (eGFR) in nonproteinuric type 2 diabetic patients.

Methods

We characterized 888 nonproteinuric type 2 diabetic patients residing in Singapore according to their eGFR values. Proteinuria was excluded on the basis of multiple urinalyses. Patients with low renal function (cases, n = 125) and controls (n = 763) were defined as having eGFR < and ≥60 mL/min/1.73 m², respectively. Pentosidine levels were measured by enzyme-linked immunosorbent assay. Multinomial logistic regression was used to test the association between plasma pentosidine levels and the joint phenotype of cataract and low eGFR.

Results

Cases had higher triacylglycerol values, higher systolic blood pressure, and were more likely to be treated with two or more antihypertensive medications. In univariate analysis, cases were potentially more than twice as likely to have had a history of cataract compared with controls. This association persisted in multivariate analyses after adjusting for the significant covariates, hypertension and triacylglycerol, but was attenuated when age was included in the model. Plasma pentosidine levels were significantly higher in cases with low eGFR who also had a history of cataract. This association persisted in multivariate analyses that included the covariates, glycosylated hemoglobin, hypertension, and diabetic retinopathy, as well as age.

Conclusion

Carbonyl stress, as reflected by pentosidine levels, is present in a subset of nonproteinuric diabetic patients. Clinically, this stress was associated with the joint presence of cataract and low eGFR.

Keywords:

• advanced glycation endproducts
• Chinese
• normoalbuminuria
• renal function

Supplementary tables

Table S1 Multivariate analysis of the joint phenotype of low eGFR and history of cataract with plasma pentosidine levels analyzed as a continuous variable

Table S2. Multivariate analysis of the joint phenotype of low estimated glomerular filtration rate and history of cataract surgery with plasma pentosidine levels as a binary variable

Table S3. Multivariate analysis of the joint phenotype of low estimated glomerular filtration rate and history of cataract surgery with plasma pentosidine levels analyzed as a continuous variable

Acknowledgments

This study was supported by a grant (NMRC/1018/2005) from the National Medical Research Council, Singapore. We thank staff and patients from the Clementi Polyclinic of National Healthcare Group Polyclinics as well as the staff of the National University of Singapore for contributing to the establishment of the Singapore Diabetes Cohort Study. We also thank Marjorie E Dunlop (University of Melbourne) and Marian Klinger (Wroclaw Medical University, Poland) for their comments on the manuscript. B-WT is supported by grants from the Ministry of Education Academic Research Fund awarded by the National University of Singapore Yong Loo Lin School of Medicine Faculty Research Committee and the Venerable Yen Pei-NKF Research Fund awarded by the National Kidney Foundation of Singapore Research Committee. B-WT is a recipient of the National Medical Research Council Overseas Fellowship Award 2009 for research studies in kidney function.

Disclosure

The authors report no conflict of interests in this work.