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Amino Acids

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Carnosinase concentration, activity, and CNDP1 genotype in patients with type 2 diabetes with and without nephropathy

  • Shiqi Zhang
  • Thomas Albrecht
  • Angelica Rodriguez-Niño
  • Jiedong Qiu
  • Peter Schnuelle
  • Verena Peters
  • Claus Peter Schmitt
  • Jacob van den Born
  • Stephan J. L. Bakker
  • Alexander Lammert
  • Bernhard K. Krämer
  • Benito A. Yard
  • Sibylle J. Hauske
Original Article
  • 54 Downloads

Abstract

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.

Keywords

Diabetes Nephropathy Carnosinase Dialysis 

Notes

Acknowledgements

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.

Ethical approval

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).

Supplementary material

726_2018_2692_MOESM1_ESM.jpg (118 kb)
Supplementary material 1 (Correlation between renal function and CNDP1 levels/activities in T2D and non-diabetic controls with preserved renal function are depicted. This figure is identical to figure 1 of the main manuscript for the groups of T2D patients but also contains CNDP1 concentrations (bar diagram to the left) and activities (bar diagram to the right) of non-diabetic controls with normal renal function for comparison. Note that CNDP1 concentration, but not activity, in T2D patients with preserved renal function is significantly higher (p<0.01 oneway ANOVA with Bonferroni’s test as post hoc test) as compared to the non-diabetic controls)
726_2018_2692_MOESM2_ESM.docx (19 kb)
Supplementary material 2 (Demographic and clinic data of all patients)

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Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2019

Authors and Affiliations

  • Shiqi Zhang
    • 1
    • 2
  • Thomas Albrecht
    • 1
  • Angelica Rodriguez-Niño
    • 1
  • Jiedong Qiu
    • 1
  • Peter Schnuelle
    • 1
  • Verena Peters
    • 3
  • Claus Peter Schmitt
    • 3
  • Jacob van den Born
    • 4
  • Stephan J. L. Bakker
    • 4
  • Alexander Lammert
    • 1
  • Bernhard K. Krämer
    • 1
  • Benito A. Yard
    • 1
  • Sibylle J. Hauske
    • 1
  1. 1.Vth Department of Medicine (Nephrology/Endocrinology/Rheumatology) University Medical Center MannheimUniversity of HeidelbergMannheimGermany
  2. 2.Department of EndocrinologyThe First Affiliated Hospital of Anhui Medical UniversityHefei ShiChina
  3. 3.Centre for Pediatric and Adolescent MedicineUniversity of HeidelbergHeidelbergGermany
  4. 4.Nephrology, University Medical Center Groningen, University of GroningenGroningenThe Netherlands

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