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Plasma Fucosylated Glycans and C-Reactive Protein as Biomarkers of HNF1A-MODY in Young Adult-Onset Nonautoimmune Diabetes.

Abstract：

OBJECTIVE:Maturity-onset diabetes of the young (MODY) due to variants in HNF1A is the most common 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 high-sensitivity C-reactive protein (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.

journal_name

Diabetes Care

journal_title

Diabetes care

authors

Juszczak A,Pavić T,Vučković F,Bennett AJ,Shah N,Pape Medvidović E,Groves CJ,Šekerija M,Chandler K,Burrows C,Rojnić Putarek N,Vučić Lovrenčić M,Ćuća Knežević J,James TJ,Gloyn AL,Lauc G,McCarthy MI,Owen KR,Gornik O

doi

10.2337/dc18-0422

subject

Has Abstract

pub_date

2019-01-01 00:00:00

pages

17-26

issue

eissn

0149-5992

issn

1935-5548

pii

dc18-0422

journal_volume

pub_type

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Plasma Fucosylated Glycans and C-Reactive Protein as Biomarkers of HNF1A-MODY in Young Adult-Onset Nonautoimmune Diabetes.