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Elevations in blood glucose before and after the appearance of islet autoantibodies in children
Katharina Warncke, … , Anette-G. Ziegler, for the GPPAD and POInT Study Groups
Katharina Warncke, … , Anette-G. Ziegler, for the GPPAD and POInT Study Groups
Published October 17, 2022
Citation Information: J Clin Invest. 2022;132(20):e162123. https://doi.org/10.1172/JCI162123.
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Research Article Immunology Article has an altmetric score of 187

Elevations in blood glucose before and after the appearance of islet autoantibodies in children

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Abstract

The etiology of type 1 diabetes has polygenic and environmental determinants that lead to autoimmune responses against pancreatic β cells and promote β cell death. The autoimmunity is considered silent without metabolic consequences until late preclinical stages,and it remains unknown how early in the disease process the pancreatic β cell is compromised. To address this, we investigated preprandial nonfasting and postprandial blood glucose concentrations and islet autoantibody development in 1,050 children with high genetic risk of type 1 diabetes. Pre- and postprandial blood glucose decreased between 4 and 18 months of age and gradually increased until the final measurements at 3.6 years of age. Determinants of blood glucose trajectories in the first year of life included sex, body mass index, glucose-related genetic risk scores, and the type 1 diabetes–susceptible INS gene. Children who developed islet autoantibodies had early elevations in blood glucose concentrations. A sharp and sustained rise in postprandial blood glucose was observed at around 2 months prior to autoantibody seroconversion, with further increases in postprandial and, subsequently, preprandial values after seroconversion. These findings show heterogeneity in blood glucose control in infancy and early childhood and suggest that islet autoimmunity is concurrent or subsequent to insults on the pancreatic islets.

Authors

Katharina Warncke, Andreas Weiss, Peter Achenbach, Thekla von dem Berge, Reinhard Berner, Kristina Casteels, Lidia Groele, Konstantinos Hatzikotoulas, Angela Hommel, Olga Kordonouri, Helena Elding Larsson, Markus Lundgren, Benjamin A. Marcus, Matthew D. Snape, Agnieszka Szypowska, John A. Todd, Ezio Bonifacio, Anette-G. Ziegler, for the GPPAD and POInT Study Groups

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Figure 3

Pre- and postprandial blood glucose concentrations in relation to age and islet autoantibody development.

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Pre- and postprandial blood glucose concentrations in relation to age an...
(A) Linear regression of preprandial glucose values (10 minutes before food intake) by visit age in the infancy period (visits 1–4; 4 months–1.35 years of age) and the toddler period (visits 5–9; 1.5–3.6 years of age) in islet autoantibody–positive children (blue; n = 443 measurements from 77 children) and autoantibody-negative children (red; n = 5,242 measurements from 973 children). (B) Linear regression of postprandial blood glucose values at 30 minutes after food intake during the infancy period in islet autoantibody–positive children (blue) and autoantibody-negative children (red). (C) Locally weighted scatterplot smoothing (LOESS) of preprandial blood glucose values (10 minutes before food intake; light blue) and postprandial blood glucose values (30 minutes after food intake; dark blue) in islet autoantibody–positive children in relation to the timing of islet autoantibody appearance (seroconversion), where blood glucose is expressed as the difference from the mean value corrected by age in islet autoantibody–negative children. The horizontal dotted line indicates no difference (0), and the vertical dotted line corresponds to the timing of seroconversion.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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