University of Oulu

Helminen, O., Pokka, T., Aspholm, S., Ilonen, J., Simell, O. G., Knip, M., & Veijola, R. (2022). First-emerging islet autoantibody and glucose metabolism: search for type 1 diabetes subtypes, Endocrine Connections, 11(9), e210632. Retrieved May 24, 2023, from

First-emerging islet autoantibody and glucose metabolism : search for type 1 diabetes subtypes

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Author: Helminen, Olli1,2; Pokka, Tytti1; Aspholm, Susanna3;
Organizations: 1Department of Pediatrics, PEDEGO Research Group, Medical Research Center, Oulu University, Hospital and University of Oulu, Oulu, Finland
2Surgery Research Unit, Cancer and Translational Medicine Research Unit, Medical Research Center Oulu, University of Oulu and Oulu University Hospital, Oulu, Finland
3Tampere Centre for Child Health Research, Tampere University Hospital, Tampere, Finland
4Immunogenetics Laboratory, University of Turku, Turku, Finland Department of Pediatrics, University of Turku and Turku University Hospital, Turku, Finland
5Department of Pediatrics, University of Turku and Turku University Hospital, Turku, Finland
6Pediatric Research Center, New Children’s Hospital, Helsinki University Hospital, Helsinki, Finland
7Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.2 MB)
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Language: English
Published: Bioscientifica, 2022
Publish Date: 2023-05-24


Objectives: Subtypes in type 1 diabetes pathogenesis have been implicated based on the first-appearing autoantibody (primary autoantibody). We set out to describe the glucose metabolism in preclinical diabetes in relation to the primary autoantibody in children with HLA-conferred disease susceptibility.

Design and methods: Dysglycemic markers are defined as a 10% increase in HbA1c in a 3–12 months interval or HbA1c ≥5.9% (41 mmol/mol) in two consecutive samples, impaired fasting glucose or impaired glucose tolerance, or a random plasma glucose value ≥7.8 mmol/L. A primary autoantibody could be detected in 295 children who later developed at least 1 additional biochemical autoantibody. These children were divided into three groups: insulin autoantibody (IAA) multiple (n  = 143), GAD antibody (GADA) multiple (n  = 126) and islet antigen 2 antibody (IA-2A) multiple (n  = 26). Another 229 children seroconverted to positivity only for a single biochemical autoantibody and were grouped as IAA only (n  = 87), GADA only (n   = 114) and IA-2A only (n  = 28).

Results: No consistent differences were observed in selected autoantibody groups during the preclinical period. At diagnosis, children with IAA only showed the highest HbA1c (P < 0.001 between groups) and the highest random plasma glucose (P = 0.005 between groups). Children with IA-2A only progressed to type 1 diabetes as frequently as those with IA-2A multiple (46% vs 54%, P = 0.297) whereas those with IAA only or GADA only progressed less often than children with IAA multiple or GADA multiple (22% vs 62% (P < 0.001) and 7% vs 43% (P < 0.001)), respectively.

Conclusions: The phenotype of preclinical diabetes defined by the primary autoantibody is not associated with any discernible differences in glucose metabolism before the clinical disease manifestation.

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Series: Endocrine connections
ISSN: 2049-3614
ISSN-E: 2049-3614
ISSN-L: 2049-3614
Volume: 11
Issue: 9
Article number: e210632
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
Funding: This work was supported by the following grants. International: JDRF International (grants 4-1998-274, 4-1999-731, 4-2001-435); European Union (grant BMH4-CT98-3314); Novo Nordisk Foundation. Finland: Academy of Finland (Centre of Excellence in Molecular Systems Immunology and Physiology Research 2012-2017, Decision No. 250114); TEKES National Technology Agency of Finland; Special Research Funds for University Hospitals in Finland; Finnish Office for Health Technology Assessment; Diabetes Research Foundation, Finland; Sigrid Juselius Foundation; Emil Aaltonen Foundation; Jalmari and Rauha Ahokas Foundation; Signe and Ane Gyllenberg Foundation; the Research Foundation of Orion Corporation; Foundation for Pediatric Research; Alma and KA Snellman Foundation; Päivikki and Sakari Sohlberg Foundation, the Finnish Medical Foundation and Finnish Cultural Foundation, Northern Ostrobothnia Regional Fund.
Copyright information: © 2022 The authors. Published by Bioscientifica Ltd. This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.