title: Apolipoprotein M can discriminate HNF1A-MODY from Type 1 diabetes.
abstract: OBJECTIVE
  Missed diagnosis of maturity-onset diabetes of the young (MODY) has led to an interest in biomarkers that enable efficient prioritization of patients for definitive molecular testing. Apolipoprotein M (apoM) was suggested as a biomarker for hepatocyte nuclear factor 1 alpha (HNF1A)-MODY because of its reduced expression in Hnf1a(-/-)  mice. However, subsequent human studies examining apoM as a biomarker have yielded conflicting results. We aimed to evaluate apoM as a biomarker for HNF1A-MODY using a highly specific and sensitive ELISA.
  
  
  METHODS
  ApoM concentration was measured in subjects with HNF1A-MODY (n = 69), Type 1 diabetes (n = 50), Type 2 diabetes (n = 120) and healthy control subjects (n = 100). The discriminative accuracy of apoM and of the apoM/HDL ratio for diabetes aetiology was evaluated.
  
  
  RESULTS
  Mean (standard deviation) serum apoM concentration (μmol/l) was significantly lower for subjects with HNF1A-MODY [0.86 (0.29)], than for those with Type 1 diabetes [1.37 (0.26), P = 3.1 × 10(-18) ) and control subjects [1.34 (0.22), P = 7.2 × 10(-19) ). There was no significant difference in apoM concentration between subjects with HNF1A-MODY and Type 2 diabetes [0.89 (0.28), P = 0.13]. The C-statistic measure of discriminative accuracy for apoM was 0.91 for HNF1A-MODY vs. Type 1 diabetes, indicating high discriminative accuracy. The apoM/HDL ratio was significantly lower in HNF1A-MODY than other study groups. However, this ratio did not perform well in discriminating HNF1A-MODY from either Type 1 diabetes (C-statistic = 0.79) or Type 2 diabetes (C-statistic = 0.68).
  
  
  CONCLUSIONS
  We confirm an earlier report that serum apoM levels are lower in HNF1A-MODY than in controls. Serum apoM provides good discrimination between HNF1A-MODY and Type 1 diabetes and warrants further investigation for clinical utility in diabetes diagnostics.
authors.affiliation: Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
authors.forename: S A
authors.initials: SA
authors.lastname: Mughal
authors.forename: R
authors.initials: R
authors.lastname: Park
authors.forename: N
authors.initials: N
authors.lastname: Nowak
authors.forename: A L
authors.initials: AL
authors.lastname: Gloyn
authors.forename: F
authors.initials: F
authors.lastname: Karpe
authors.forename: H
authors.initials: H
authors.lastname: Matile
authors.forename: M T
authors.initials: MT
authors.lastname: Malecki
authors.forename: M I
authors.initials: MI
authors.lastname: McCarthy
authors.forename: M
authors.initials: M
authors.lastname: Stoffel
authors.forename: K R
authors.initials: KR
authors.lastname: Owen
mesh_terms: D000328:Adult; D017668:Age of Onset; D000818:Animals; D001053:Apolipoproteins / Q000097:blood*; D000075243:Apolipoproteins M; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000175:diagnosis / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000175:diagnosis / Q000235:genetics; D003937:Diagnosis, Differential; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005786:Gene Expression Regulation; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000378:metabolism*; D006801:Humans; D054834:Lipocalins / Q000097:blood*; D008297:Male; D051379:Mice; D020125:Mutation, Missense / Q000235:genetics; D015203:Reproducibility of Results
chemical_list: C400523:APOM protein, human; D001053:Apolipoproteins; D000075243:Apolipoproteins M; D015415:Biomarkers; C496487:HNF1A protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D054834:Lipocalins