期刊
DIABETOLOGIA
卷 54, 期 11, 页码 2801-2810出版社
SPRINGER
DOI: 10.1007/s00125-011-2261-y
关键词
Biomarker; High-sensitivity C-reactive protein; hsCRP; Maturity-onset diabetes of the young; MODY
资金
- NIHR
- Medical Research Council (MRC) [81696]
- University of Bergen, Helse Vest, Innovest
- Research Council of Norway
- BITCET
- VEGA [2/0151/11]
- Oxford (NIHR) Biomedical Research Centre
- European Community [HEALTH-F2-2008-223211, HEALTH-F4-2007-201413]
- Lundbeck Foundation Centre for Applied Medical Genomics in Personalized Disease Prediction, Prevention and Care (LuCAMP)
- Danish Diabetes Association
- Danish Research Council
- Novo Nordisk Foundation
- Diabetes UK
- Medical Research Council [G0700222] Funding Source: researchfish
- National Institute for Health Research [DHCS/07/07/008] Funding Source: researchfish
- MRC [G0700222] Funding Source: UKRI
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.
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