The Journal of Clinical Investigation (Oct 2022)

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

  • 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

Journal volume & issue
Vol. 132, no. 20

Abstract

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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.

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