Diabetologie und Stoffwechsel 2015; 10 - P160
DOI: 10.1055/s-0035-1549666

Carnosinase concentration and activity in CNDP1 (CTG)5 homozygous T2DM patients with and without nephropathy

S Zhang 1, F Pfister 2, H Lindner 1, T Albrecht 1, S Classen 1, S Kabtni 1, V Peters 3, C Klessens 3, J van den Born 4, G Navis 4, S Bakker 4, E de Heer 5, B Krämer 1, B Yard 1, S Hauske 1
  • 1Medical Faculty Mannheim of Heidelberg University, Mannheim, Germany
  • 2Institute of Pathology, Universitätsklinikum Erlangen, Erlangen, Germany
  • 3Centre for Pediatric and Adolescent Medicine, University of Heidelberg, Heidelberg, Germany
  • 4University Medical Center Groningen, University of Groningen, Groningen, Netherlands
  • 5Leiden University Medical Center, Leiden, Netherlands

This study assessed if serum carnosinase (CN-1) activity, concentration and conformation in Type 2 diabetes mellitus (T2DM) patients carrying the protective CNDP1 genotype ((CTG)5 homozygous) with diabetic nephropathy (DN) differ from those without nephropathy.

In a cross-sectional design 127 T2DM patients with DN and 145 T2DM patients without nephropathy were recruited. Additional control groups, i.e, non- diabetic controls (n = 111) and uraemic controls (n = 85) were included for assessing confounders.

CNDP1 (CTG)5 homozygous T2DM patients with DN had significantly lower CN-1 concentrations (30.4 ± 18.3 vs. 51.2 ± 17.6 µg/ml) and activity (1.25 ± 0.5 vs. 2.53 ± 1.1µmol ml-1 h-1, p < 0.05) than those without nephropathy. CN-1 concentrations correlated with BMI and renal function as assessed by estimated GFR. Carnosinasuria was detected in patients with micro- or macro-albuminuria (range 39 – 836 ng/ml), correlated negatively with serum albumin (r2: 0.90) and positively with albuminuria (r2: 0.83). In kidney biopsies from patients with DN and persistent proteinuria or from patients with membranous glomerulonephritis, CN-1 expression was increased in proximal tubules (0.014 ± 0.021 vs. 0.102 ± 0.130) as compared to normal kidneys.

Our study demonstrates that serum CN-1 concentrations in T2DM patients with DN are decreased, possibly as a consequence of protein energy wasting and carnosinasuria. This is the first report on carnosinasuria in T2DM patients ever. Our data warrant further studies using large cohorts to underpin these initial findings and to delineate the relevance of carnosinasuria for renal function deterioration.