| A large multi-centre European study validates high-sensitivity C-reactive protein (hsCRP) as a clinical biomarker for the diagnosis of diabetes subtypes. | |
| | |
MedLine Citation:
|
PMID: 21814873 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
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 |
Related Documents
:
|
19796383 - Effects of a fibre-enriched milk drink on insulin and glucose levels in healthy subjects. 21474403 - Hba(1c) values for defining diabetes and impaired fasting glucose in asian indians. 17306503 - Pioglitazone improves insulin action and normalizes menstrual cycles in a majority of p... |
Publication Detail:
|
Type: Comparative Study; Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't; Validation Studies Date: 2011-08-04 |
Journal Detail:
|
Title: Diabetologia Volume: 54 ISSN: 1432-0428 ISO Abbreviation: Diabetologia Publication Date: 2011 Nov |
Date Detail:
|
Created Date: 2011-10-07 Completed Date: 2012-03-01 Revised Date: 2012-05-23 |
Medline Journal Info:
|
Nlm Unique ID: 0006777 Medline TA: Diabetologia Country: Germany |
Other Details:
|
Languages: eng Pagination: 2801-10 Citation Subset: IM |
Affiliation:
|
Oxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Headington, Oxford, OX3 7LJ, UK. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adult Age of Onset Biological Markers / blood C-Reactive Protein / analysis* Diabetes Mellitus, Type 2 / blood*, diagnosis, genetics* Europe Glucokinase / chemistry, genetics Hepatocyte Nuclear Factor 1-alpha / chemistry, genetics* Hepatocyte Nuclear Factor 4 / chemistry, genetics Heterozygote Humans Meta-Analysis as Topic Middle Aged Molecular Diagnostic Techniques* Mutation Reproducibility of Results Sensitivity and Specificity Young Adult |
| Grant Support | |
ID/Acronym/Agency:
|
G0700222(81696)//Medical Research Council |
| Chemical | |
Reg. No./Substance:
|
0/Biological Markers; 0/HNF1A protein, human; 0/HNF4A protein, human; 0/Hepatocyte Nuclear Factor 1-alpha; 0/Hepatocyte Nuclear Factor 4; 9007-41-4/C-Reactive Protein; EC 2.7.1.2/Glucokinase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Changes of Fecal Bifidobacterium Species in Adult Patients with Hepatitis B Virus-Induced Chronic Li...
Next Document: Comparative study of hypocholesterolemic and hypolipidemic effects of conjugated linolenic acid isom...