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A large multi-centr...
A large multi-centre European study validates high-sensitivity C-reactive protein (hsCRP) as a clinical biomarker for the diagnosis of diabetes subtypes
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Thanabalasingham, G. (author)
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Shah, N. (author)
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Vaxillaire, M. (author)
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Hansen, T. (author)
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Tuomi, T. (author)
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Gasperikova, D. (author)
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Szopa, M. (author)
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Tjora, E. (author)
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James, T. J. (author)
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Kokko, P. (author)
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Loiseleur, F. (author)
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Andersson, E. (author)
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Gaget, S. (author)
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Isomaa, B. (author)
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Nowak, N. (author)
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Raeder, H. (author)
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Stanik, J. (author)
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Njolstad, P. R. (author)
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Malecki, M. T. (author)
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Klimes, I. (author)
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- Groop, Leif (author)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
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Pedersen, O. (author)
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Froguel, P. (author)
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McCarthy, M. I. (author)
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Gloyn, A. L. (author)
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Owen, K. R. (author)
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(creator_code:org_t)
- 2011-08-04
- 2011
- English.
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In: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 54:11, s. 2801-2810
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Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Keyword
- Biomarker
- High-sensitivity C-reactive protein
- hsCRP
- Maturity-onset
- diabetes of the young
- MODY
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Thanabalasingham ...
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Shah, N.
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Vaxillaire, M.
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Hansen, T.
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Tuomi, T.
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Gasperikova, D.
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show more...
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Szopa, M.
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Tjora, E.
-
James, T. J.
-
Kokko, P.
-
Loiseleur, F.
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Andersson, E.
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Gaget, S.
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Isomaa, B.
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Nowak, N.
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Raeder, H.
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Stanik, J.
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Njolstad, P. R.
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Malecki, M. T.
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Klimes, I.
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Groop, Leif
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Pedersen, O.
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Froguel, P.
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McCarthy, M. I.
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Gloyn, A. L.
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Owen, K. R.
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show less...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
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Diabetologia
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Lund University