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HbA1c as a time predictive biomarker for an additional islet autoantibody and type 1 diabetes in seroconverted TEDDY children

Salami, Falastin LU ; Tamura, Roy ; You, Lu ; Lernmark, Åke LU orcid ; Elding Larsson, Helena LU ; Lundgren, Markus LU ; Krischer, Jeffrey ; Ziegler, Anette-Gabriele ; Toppari, Jorma and Veijola, Riitta LU , et al. (2022) In Pediatric Diabetes 23(8). p.1586-1593
Abstract

BACKGROUND/OBJECTIVES: Increased level of glycated hemoglobin (HbA1c) is associated with type 1 diabetes onset that in turn is preceded by one to several autoantibodies against the pancreatic islet beta cell autoantigens; insulin (IA), glutamic acid decarboxylase (GAD), islet antigen-2 (IA-2) and zinc transporter 8 (ZnT8). The risk for type 1 diabetes diagnosis increases by autoantibody number. Biomarkers predicting the development of a second or a subsequent autoantibody and type 1 diabetes are needed to predict disease stages and improve secondary prevention trials. This study aimed to investigate whether HbA1c possibly predicts the progression from first to a subsequent autoantibody or type 1 diabetes in healthy children... (More)

BACKGROUND/OBJECTIVES: Increased level of glycated hemoglobin (HbA1c) is associated with type 1 diabetes onset that in turn is preceded by one to several autoantibodies against the pancreatic islet beta cell autoantigens; insulin (IA), glutamic acid decarboxylase (GAD), islet antigen-2 (IA-2) and zinc transporter 8 (ZnT8). The risk for type 1 diabetes diagnosis increases by autoantibody number. Biomarkers predicting the development of a second or a subsequent autoantibody and type 1 diabetes are needed to predict disease stages and improve secondary prevention trials. This study aimed to investigate whether HbA1c possibly predicts the progression from first to a subsequent autoantibody or type 1 diabetes in healthy children participating in the Environmental Determinants of Diabetes in the Young (TEDDY) study.

METHODS: A joint model was designed to assess the association of longitudinal HbA1c levels with the development of first (insulin or GAD autoantibodies) to a second, second to third, third to fourth autoantibody or type 1 diabetes in healthy children prospectively followed from birth until 15 years of age.

RESULTS: It was found that increased levels of HbA1c were associated with a higher risk of type 1 diabetes (HR 1.82, 95% CI [1.57-2.10], p<0.001) regardless of first appearing autoantibody, autoantibody number or type. A decrease in HbA1c levels was associated with the development of IA-2A as a second autoantibody following GADA (HR 0.85, 95% CI [0.75,0.97], p=0.017) and a fourth autoantibody following GADA, IAA and ZnT8A (HR 0.90, 95% CI [0.82,0.99], p=0.036). HbA1c trajectory analyses showed a significant increase of HbA1c over time (p<0.001) and that the increase is more rapid as the number of autoantibodies increased from one to three (p<0.001).

CONCLUSION: In conclusion, increased HbA1c is a reliable time predictive marker for type 1 diabetes onset. The increased rate of increase of HbA1c from first to third autoantibody and the decrease in HbA1c predicting the development of IA-2A are novel findings proving the link between HbA1c and the appearance of autoantibodies. This article is protected by copyright. All rights reserved.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Pediatric Diabetes
volume
23
issue
8
pages
1586 - 1593
publisher
Wiley-Blackwell
external identifiers
  • scopus:85138410387
  • pmid:36082496
ISSN
1399-543X
DOI
10.1111/pedi.13413
language
English
LU publication?
yes
additional info
This article is protected by copyright. All rights reserved.
id
008fc93f-7c08-4112-81cc-6d14171803fa
date added to LUP
2022-09-14 10:09:36
date last changed
2024-04-15 03:52:41
@article{008fc93f-7c08-4112-81cc-6d14171803fa,
  abstract     = {{<p>BACKGROUND/OBJECTIVES: Increased level of glycated hemoglobin (HbA1c) is associated with type 1 diabetes onset that in turn is preceded by one to several autoantibodies against the pancreatic islet beta cell autoantigens; insulin (IA), glutamic acid decarboxylase (GAD), islet antigen-2 (IA-2) and zinc transporter 8 (ZnT8). The risk for type 1 diabetes diagnosis increases by autoantibody number. Biomarkers predicting the development of a second or a subsequent autoantibody and type 1 diabetes are needed to predict disease stages and improve secondary prevention trials. This study aimed to investigate whether HbA1c possibly predicts the progression from first to a subsequent autoantibody or type 1 diabetes in healthy children participating in the Environmental Determinants of Diabetes in the Young (TEDDY) study.</p><p>METHODS: A joint model was designed to assess the association of longitudinal HbA1c levels with the development of first (insulin or GAD autoantibodies) to a second, second to third, third to fourth autoantibody or type 1 diabetes in healthy children prospectively followed from birth until 15 years of age.</p><p>RESULTS: It was found that increased levels of HbA1c were associated with a higher risk of type 1 diabetes (HR 1.82, 95% CI [1.57-2.10], p&lt;0.001) regardless of first appearing autoantibody, autoantibody number or type. A decrease in HbA1c levels was associated with the development of IA-2A as a second autoantibody following GADA (HR 0.85, 95% CI [0.75,0.97], p=0.017) and a fourth autoantibody following GADA, IAA and ZnT8A (HR 0.90, 95% CI [0.82,0.99], p=0.036). HbA1c trajectory analyses showed a significant increase of HbA1c over time (p&lt;0.001) and that the increase is more rapid as the number of autoantibodies increased from one to three (p&lt;0.001).</p><p>CONCLUSION: In conclusion, increased HbA1c is a reliable time predictive marker for type 1 diabetes onset. The increased rate of increase of HbA1c from first to third autoantibody and the decrease in HbA1c predicting the development of IA-2A are novel findings proving the link between HbA1c and the appearance of autoantibodies. This article is protected by copyright. All rights reserved.</p>}},
  author       = {{Salami, Falastin and Tamura, Roy and You, Lu and Lernmark, Åke and Elding Larsson, Helena and Lundgren, Markus and Krischer, Jeffrey and Ziegler, Anette-Gabriele and Toppari, Jorma and Veijola, Riitta and Rewers, Marian and Haller, Michael J and Hagopian, William and Akolkar, Beena and Törn, Carina}},
  issn         = {{1399-543X}},
  language     = {{eng}},
  month        = {{09}},
  number       = {{8}},
  pages        = {{1586--1593}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Pediatric Diabetes}},
  title        = {{HbA1c as a time predictive biomarker for an additional islet autoantibody and type 1 diabetes in seroconverted TEDDY children}},
  url          = {{http://dx.doi.org/10.1111/pedi.13413}},
  doi          = {{10.1111/pedi.13413}},
  volume       = {{23}},
  year         = {{2022}},
}