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A large multi-centre European study validates high-sensitivity C-reactive protein (hsCRP) as a clinical biomarker for the diagnosis of diabetes subtypes

In English

Författare

  • G. Thanabalasingham
  • N. Shah
  • M. Vaxillaire
  • T. Hansen
  • T. Tuomi
  • D. Gasperikova
  • 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
  • Leif Groop
  • O. Pedersen
  • P. Froguel
  • M. I. McCarthy
  • A. L. Gloyn
  • K. R. Owen
Visa allt

Summary, in English

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. 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. 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 x 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 x 10(-5)). High-sensitivity CRP values between assays were strongly correlated (r (2) a parts per thousand yenaEuro parts per thousand 0.91, p a parts per thousand currency signaEuro parts per thousand 1 x 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. 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.

Publiceringsår

2011

Språk

Engelska

Sidor

2801-2810

Publikation/Tidskrift/Serie

Diabetologia

Volym

54

Issue

11

Dokumenttyp

Artikel i tidskrift

Förlag

Springer

Ämne

  • Endocrinology and Diabetes

Nyckelord

  • Biomarker
  • High-sensitivity C-reactive protein
  • hsCRP
  • Maturity-onset
  • diabetes of the young
  • MODY

Status

Published

Forskningsgrupp

  • Genomics, Diabetes and Endocrinology

ISBN/ISSN/Övrigt

  • ISSN: 1432-0428