High-Sensitivity CRP Discriminates HNF1A-MODY From Other Subtypes of Diabetes

  1. Andrew T. Hattersley, DM1
  1. 1Peninsula College of Medicine and Dentistry (University of Exeter), Peninsula NIHR Clinical Research Facility, Exeter, Devon, U.K.
  2. 2Royal Devon and Exeter NHS Foundation Trust, Department of Clinical Chemistry, Exeter, Devon, U.K.
  3. 3University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford, U.K.
  4. 4Churchill Hospital, Oxford National Institute for Health Research Biomedical Research Centre, Oxford, U.K.
  5. 5Royal Devon and Exeter NHS Foundation Trust, Department of Molecular Genetics, Exeter, U.K.
  1. Corresponding author: Tim J. McDonald, tim.mcdonald{at}rdeft.nhs.uk.

Abstract

OBJECTIVE Maturity-onset diabetes of the young (MODY) as a result of mutations in hepatocyte nuclear factor 1-α (HNF1A) is often misdiagnosed as type 1 diabetes or type 2 diabetes. Recent work has shown that high-sensitivity C-reactive protein (hs-CRP) levels are lower in HNF1A-MODY than type 1 diabetes, type 2 diabetes, or glucokinase (GCK)-MODY. We aim to replicate these findings in larger numbers and other MODY subtypes.

RESEARCH DESIGN AND METHODS hs-CRP levels were assessed in 750 patients (220 HNF1A, 245 GCK, 54 HNF4-α [HNF4A], 21 HNF1-β (HNF1B), 53 type 1 diabetes, and 157 type 2 diabetes).

RESULTS hs-CRP was lower in HNF1A-MODY (median [IQR] 0.3 [0.1–0.6] mg/L) than type 2 diabetes (1.40 [0.60–3.45] mg/L; P < 0.001) and type 1 diabetes (1.10 [0.50–1.85] mg/L; P < 0.001), HNF4A-MODY (1.45 [0.46–2.88] mg/L; P < 0.001), GCK-MODY (0.60 [0.30–1.80] mg/L; P < 0.001), and HNF1B-MODY (0.60 [0.10–2.8] mg/L; P = 0.07). hs-CRP discriminated HNF1A-MODY from type 2 diabetes with hs-CRP <0.75 mg/L showing 79% sensitivity and 70% specificity (receiver operating characteristic area under the curve = 0.84).

CONCLUSIONS hs-CRP levels are lower in HNF1A-MODY than other forms of diabetes and may be used as a biomarker to select patients for diagnostic HNF1A genetic testing.

Footnotes

  • Received February 16, 2011.
  • Accepted May 14, 2011.

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  1. Diabetes Care vol. 34 no. 8 1860-1862
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