Exp Clin Endocrinol Diabetes 2006; 114 - P12_150
DOI: 10.1055/s-2006-933035

Association of chemokine levels with C-peptide, HbA1c and proinsulin in patients with newly diagnosed diabetes mellitus type 1. Results from the Hvidøre study group

C Pfleger 1, NC Schloot 1, H Kolb 1, P Hougaard 2, R Holl 3, L Hansen 4 HB Mortensen 5, and the Hvidøre Study Group on Childhood Diabetes
  • 1German Diabetes Research Institute at the Heinrich-Heine University Duesseldorf, Clinical department, Düsseldorf, Germany
  • 2University of Southern Denmark, Statistical department, Odense, Denmark
  • 3University of Ulm, Department of Paediatrics, Ulm, Germany
  • 4Novo Nordisk A/S, Preclinical development, Bagsværd, Denmark
  • 5Glostrup University Hospital, Department of Paediatrics, Glostrup, Denmark

Objectives: The aim of the current study was to investigate circulating levels of the CCR5 ligand MIP-1ß and RANTES and their relation with and prediction of residual ß-cell capacity during the first 12 months after onset of type 1 diabetes (T1D) in children and adolescents.

Methods: Serum was obtained from 256 newly diagnosed patients with T1D. HbA1c, stimulated C-peptide and proinsulin were determined. Serum cytokines and chemokines were measured by double sandwich ELISA. Data were analysed by multiple logistic regression analysis including gender, age, IL6, CCL4/MIP1ß, CCL5/ RANTES and MIF as co-variates, non-parametric Wilcoxon test and Spearmans correlation analysis.

Results: 1month after diabetes onset, HbA1c associated positively with RANTES (coefficient: 0.009%/ng/ml, SE 0.002, p<0.0001), while C-peptide levels related negatively with MIP1ß (coefficient: –0.12%/pg/ml, SE 0.06, p=0.0367). 6months after onset C-peptide and proinsulin levels associated negatively with MIP1ß (coefficient: -0.13%/pg/ml, SE 0.07, p=0.0588, coefficient: -0.28%/pg/ml, SE 0.09, p=0.018), while 12months after onset, only proinsulin levels associated negatively with MIP1ß coefficient: –0.31%/pg/ml, SE 0.09, p=0.0020). Prediction models for residual ß-cell function showed a negative association between MIP1ß levels at 1month and C-peptide (coefficient -0.11%/pg/ml, SE 0.07, p=0.08) and proinsulin (coefficient –0.28 SE 0.08, p=0.0004) at 6months and a negative association between proinsulin and MIP1ß levels (coefficient –0.37%/pg/ml, SE 0.01, p=0.0006) at 12months. RANTES at 1month associated positively with proinsulin (coefficient 0.53%/ng/ml, SE 0.25, p=0.03) at 6months and proinsulin (coefficient: 0.76%/ng/ml, SE 0.29, p=0.0085) at 12months.

Conclusion: It is suggested that C-peptide and proinsulin levels are associated with innate immunity chemokines in the first year after T1D manifestation. The study indicates that MIP1ß and RANTES may serve as predictive markers of disease progression and residual ß-cell function during intervention trials in T1D.