Plasma fucosylated glycans and C-reactive protein as biomarkers of HNF1A-MODY in young adult–onset nonautoimmune diabetes

Agata Juszczak, Tamara Pavić, Frano Vučković, Amanda J. Bennett, Neha Shah, Edita Pape Medvidović, Christopher J. Groves, Mario Šekerija, Kyla Chandler, Carla Burrows, Nataša Rojnić Putarek, Marijana Vučić Lovrenčić, Jadranka Ćuća Knežević, Tim J. James, Anna L. Gloyn, Gordan Lauc, Mark I. McCarthy, Katharine R. Owen*, Olga Gornik

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

12 Citations (Scopus)
368 Downloads (Pure)

Abstract

OBJECTIVE:
Maturity-onset diabetes of the young (MODY) due to variants in HNF1A is the commonest type of monogenic diabetes. Frequent misdiagnosis results in missed opportunity to use sulfonylureas as first-line treatment. A nongenetic biomarker could improve selection of subjects for genetic testing and increase diagnosis rates. We previously reported that plasma levels of antennary fucosylated N-glycans and hs-CRP are reduced in individuals with HNF1A-MODY. In this study, we examined the potential use of N-glycans and hs-CRP in discriminating individuals with damaging HNF1A alleles from those without HNF1A variants in an unselected population of young adults with nonautoimmune diabetes.

RESEARCH DESIGN AND METHODS:

We analyzed the plasma N-glycan profile, measured hs-CRP, and sequenced HNF1A in 989 individuals with diabetes diagnosed when younger than age 45, persistent endogenous insulin production, and absence of pancreatic autoimmunity. Systematic assessment of rare HNF1A variants was performed.

RESULTS:
We identified 29 individuals harboring 25 rare HNF1A alleles, of which 3 were novel, and 12 (in 16 probands) were considered pathogenic. Antennary fucosylated N-glycans and hs-CRP were able to differentiate subjects with damaging HNF1A alleles from those without rare HNF1A alleles. Glycan GP30 had a receiver operating characteristic curve area under the curve (AUC) of 0.90 (88% sensitivity, 80% specificity, cutoff 0.70%), whereas hs-CRP had an AUC of 0.83 (88% sensitivity, 69% specificity, cutoff 0.81 mg/L).

CONCLUSIONS:
Half of rare HNF1A sequence variants do not cause MODY. N-glycan profile and hs-CRP could both be used as tools, alone or as adjuncts to existing pathways, for identifying individuals at high risk of carrying a damaging HNF1A allele.
Original languageEnglish
Pages (from-to)17-26
Number of pages10
JournalDiabetes Care
Volume42
Issue number1
Early online date19 Nov 2018
DOIs
Publication statusPublished - Jan 2019

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