Carnosinase concentration, activity, and CNDP1 genotype in patients with type 2 diabetes with and without nephropathy
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This study assessed if serum carnosinase (CNDP1) activity and concentration in patients with type 2 diabetes mellitus (T2D) with diabetic nephropathy (DN) differs from those without nephropathy. In a cross-sectional design 127 patients with T2D with DN ((CTG)5 homozygous patients n = 45) and 145 patients with T2D without nephropathy ((CTG)5 homozygous patients n = 47) were recruited. Univariate and multivariate regression analyses were performed to predict factors relevant for serum CNDP1 concentration. CNDP1 (CTG)5 homozygous patients with T2D with DN had significantly lower CNDP1 concentrations (30.4 ± 18.3 vs 51.2 ± 17.6 µg/ml, p < 0.05) and activity (1.25 ± 0.5 vs 2.53 ± 1.1 µmol/ml/h, p < 0.05) than those without nephropathy. This applied for patients with DN on the whole, irrespective of (CTG)5 homozygosity. In the multivariate regression analyses, lower serum CNDP1 concentrations correlated with impaired renal function and to a lesser extend with the CNDP1 genotype (95% CI of regression coefficients: eGFR: 0.10–1.94 (p = 0.001); genotype: − 0.05 to 5.79 (p = 0.055)). Our study demonstrates that serum CNDP1 concentrations associate with CNDP1 genotype and renal function in patients with T2D. Our data warrant further studies using large cohorts to confirm these findings and to delineate the correlation between low serum CNDP1 concentrations and renal function deterioration in patients with T2D.
KeywordsDiabetes Nephropathy Carnosinase Dialysis
This work was supported by Deutsche Forschungsgemeinschaft (DFG) SA 2143/1-1 to S.J.H., YA 44/6-1 to BY, Graduiertenkolleg (GRK) 1874/1 to B.Y. and S.J.H, SFB 1118 to V.P. and C.P.S. The authors of this manuscript like to acknowledge Ms. Renate Stein and Ms. Annette Breedijk (Vth Department of Medicine, University Medical Center Mannheim, University of Heidelberg) for their assistance in performing ELISA and CNDP1 genotyping. The authors would like to thank all involved Dialysis Units and Diabetic Centers for supporting the recruitment of patients.
Compliance with ethical standards
Conflict of interest
The authors declare that there is no conflict of interest associated with this manuscript.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1984 Helsinki declaration and its later amendments or comparable ethical standards. The study protocol was approved by the local ethics committee and all patients gave their written informed consent prior to study (No. 0193/2001).
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