4.3 Article

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

期刊

PEDIATRIC DIABETES
卷 23, 期 8, 页码 1586-1593

出版社

WILEY-HINDAWI
DOI: 10.1111/pedi.13413

关键词

children; GADA; HbA1c; IA-2A; IAA; islet autoantibodies; type 1 diabetes; ZnT8A

资金

  1. Centers for Disease Control and Prevention (CDC)
  2. Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  3. Juvenile Diabetes Research Foundation United States of America
  4. National Institute of Allergy and Infectious Diseases (NIAID)
  5. NIH/NCATS Clinical and Translational Science Awards
  6. University of Colorado [UL1 TR002535]
  7. University of Florida [UL1 TR000064]
  8. National Institute of Environmental Health Sciences (NIEHS)
  9. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [HHSN267200700014C, U01 DK128847, U01 DK124166, UC4 DK117483, UC4 DK112243, UC4 DK106955, UC4 DK100238, UC4 DK95300, UC4 DK63836, UC4 DK63863, UC4 DK63865, UC4 DK63821, UC4 DK63861, UC4 DK63829, U01 DK63836, U01 DK63863, U01 DK63865, U01 DK63861, U01 DK63829]

向作者/读者索取更多资源

The study found that increased levels of HbA1c were associated with a higher risk of type 1 diabetes, while a decrease in HbA1c levels predicted the development of IA-2A autoantibody. The trajectory of HbA1c can predict the appearance of autoantibodies and the onset of type 1 diabetes.
Objective 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. Research Design and 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.

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