HbA1c as a time predictive biomarker for an additional islet autoantibody and type 1 diabetes in seroconverted TEDDY children
(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.
(Less)
- author
- author collaboration
- organization
- publishing date
- 2022-09-09
- 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<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).</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}}, }