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Falastin Salami

Research project participant

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


  • Falastin Salami
  • Roy Tamura
  • Lu You
  • Åke Lernmark
  • Helena Elding Larsson
  • Markus Lundgren
  • Jeffrey Krischer
  • Anette-Gabriele Ziegler
  • Jorma Toppari
  • Riitta Veijola
  • Marian Rewers
  • Michael J Haller
  • William Hagopian
  • Beena Akolkar
  • Carina Törn

Summary, in English

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.


  • Celiac Disease and Diabetes Unit
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • Paediatric Endocrinology

Publishing year







Pediatric Diabetes





Document type

Journal article




  • Endocrinology and Diabetes



Research group

  • Celiac Disease and Diabetes Unit
  • Paediatric Endocrinology


  • ISSN: 1399-543X