Erschienen in:
01.11.2011 | Article
A large multi-centre European study validates high-sensitivity C-reactive protein (hsCRP) as a clinical biomarker for the diagnosis of diabetes subtypes
verfasst von:
G. Thanabalasingham, N. Shah, M. Vaxillaire, T. Hansen, T. Tuomi, D. Gašperíková, M. Szopa, E. Tjora, T. J. James, P. Kokko, F. Loiseleur, E. Andersson, S. Gaget, B. Isomaa, N. Nowak, H. Raeder, J. Stanik, P. R. Njolstad, M. T. Malecki, I. Klimes, L. Groop, O. Pedersen, P. Froguel, M. I. McCarthy, A. L. Gloyn, K. R. Owen
Erschienen in:
Diabetologia
|
Ausgabe 11/2011
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Abstract
Aims/hypothesis
An accurate molecular diagnosis of diabetes subtype confers clinical benefits; however, many individuals with monogenic diabetes remain undiagnosed. Biomarkers could help to prioritise patients for genetic investigation. We recently demonstrated that high-sensitivity C-reactive protein (hsCRP) levels are lower in UK patients with hepatocyte nuclear factor 1 alpha (HNF1A)-MODY than in other diabetes subtypes. In this large multi-centre study we aimed to assess the clinical validity of hsCRP as a diagnostic biomarker, examine the genotype–phenotype relationship and compare different hsCRP assays.
Methods
High-sensitivity CRP levels were analysed in individuals with HNF1A-MODY (n = 457), glucokinase (GCK)-MODY (n = 404), hepatocyte nuclear factor 4 alpha (HNF4A)-MODY (n = 54) and type 2 diabetes (n = 582) from seven European centres. Three common assays for hsCRP analysis were evaluated. We excluded 121 participants (8.1%) with hsCRP values >10 mg/l. The discriminative power of hsCRP with respect to diabetes aetiology was assessed by receiver operating characteristic curve-derived C-statistic.
Results
In all centres and irrespective of the assay method, meta-analysis confirmed significantly lower hsCRP levels in those with HNF1A-MODY than in those with other aetiologies (z score −21.8, p < 5 × 10−105). HNF1A-MODY cases with missense mutations had lower hsCRP levels than those with truncating mutations (0.03 vs 0.08 mg/l, p < 5 × 10−5). High-sensitivity CRP values between assays were strongly correlated (r
2 ≥ 0.91, p ≤ 1 × 10−5). Across the seven centres, the C-statistic for distinguishing HNF1A-MODY from young adult-onset type 2 diabetes ranged from 0.79 to 0.97, indicating high discriminative accuracy.
Conclusions/interpretation
In the largest study to date, we have established that hsCRP is a clinically valid biomarker for HNF1A-MODY in European populations. Given the modest costs and wide availability, hsCRP could translate rapidly into clinical practice, considerably improving diagnosis rates in monogenic diabetes.