Oral Presentation ESA-SRB-APEG-NZSE 2022

Development of islet autoimmunity in Australian children at-risk of type 1 diabetes in the Environmental Determinants of Islet Autoimmunity (ENDIA)  study (#252)

Jennifer Couper 1 2 , Helena Oakey 2 , Megan Penno 2 , Kelly Watson 3 , Dao Huynh 2 , Maria Craig 4 5 , John Wentworth 3 6 , Leonard Harrison 6 , Liz Davis 7 , Aveni Haynes 7 , Mark Harris 8 , Peter Vuillermin 9 , Georgia Soldatos 10 , Simon Barry 1 , Emma Hamilton-Williams 11 , Ki Wook Kim 5 , Grant Morahan 12 , Kelly McGorm 2 , William Rawlinson 5 , Richard Sinnott 13 , Rebecca Thomson 2 , Peter Colman 3
  1. Womens and Childrens Hospital, Adelaide, SOUTH AUSTRALIA, Australia
  2. University of Adelaide , Adelaide, South Australia, Australia
  3. Diabetes and Endocrinology, Royal Melbourne Hospital, Melbourne, Vic, Australia
  4. Childrens Hospital Westmead, Sydney , NSW, Australia
  5. University of NSW, Sydney, NSW, Australia
  6. Walter and Eliza Hall Institute of Medical Research , Melbourne , Vic, Australia
  7. Telethon Institute for Child Health Research, Perth, WA, Australia
  8. Queensland Children's Hospital , Brisbane, Qld , Australia
  9. Barwon Health, Geelong, Vic, Australia
  10. Monash Health, Melbourne, Vic, Australia
  11. University of Queensland Diamantina Institute, Brisbane, Queensland, Australia
  12. Harry Perkins Institute of Medical Research , Perth, WA, Australia
  13. University of Melbourne, Melbourne, Vic, Australia

The Environmental Determinants of Islet Autoimmunity (ENDIA) study follows Australian children with a first-degree relative with type 1 diabetes (T1D) in a unique pregnancy-birth cohort. Primary outcome is the development of persistent islet autoimmunity. Of children who develop multiple islet autoantibodies in the first 5 years , 85% are predicted to progress to clinical T1D before adulthood1. We aimed to characterise the pattern of islet autoantibody seroconversion in ENDIA children.

Participants were followed prospectively 3 monthly during pregnancy and the first 2 years, and 6 monthly thereafter. Autoantibodies to insulin (IAA), GAD, IA-2 and ZnT8 were measured by radio-binding and ELISA assays.

By August 2022, 92 of 1256 (7%) children aged median 4.9 (IQR 3.7, 6.3) years had developed one or more persistent islet autoantibodies or T1D (Table 1). First appearing autoantibody was most commonly IAA in 56/92 (62%), alone or in combination, followed by ZnT8A alone in 25% and GADA alone in 13%.

Probability of progression to persistent islet autoimmunity within the first 2 years was 2% for IAA alone-first. HLA DR4/DQ8 was predominant in these children (24/38). First appearance of other autoantibodies alone reached similar probabilities after 4 years. Relative risk of development of persistent islet autoimmunity using father with T1D as reference, was ~three-fold with multiple first-degree relatives with T1D (HR = 2.8), similar with a sibling proband (HR= 0.9), and lowest with a mother proband (HR = 0.7). Twenty children progressed to T1D – one with mild ketoacidosis. IAA-first, alone or in combination, was the usual sequence (18/20).

In conclusion, the predominant pattern in at-risk young children is IAA-first peaking early in association with high risk HLA type and progression to T1D. Other autoantibodies peak later. Early life patterns of islet autoimmunity may implicate different endotypes, with different environmental drivers from pregnancy and post-natal life.

 

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  1. 1. Ziegler A et al Seroconversion to multiple islet autoantibodies and risk of progression to diabetes in children. JAMA 2013 ;309(23):2473-9. doi: 10.1001/jama.2013.6285.