Age at Development of Type 1 Diabetes and Celiac Disease-Associated Antibodies and Clinical Disease in Genetically Susceptible Children Observed from Birth

  1. Satu Simell, MD (satu.simell{at},2,
  2. Sanna Hoppu, MD, PHD1,4,
  3. Tuula Simell, MPH, PHD1,2,
  4. Marja-Riitta Ståhlberg, MD, PHD2,
  5. Markku Viander, MD, PHD3,
  6. Taina Routi, MD, PHD2,
  7. Ville Simell, MSC1,2,
  8. Riitta Veijola, MD, PHD1,5,
  9. Jorma Ilonen, MD, PHD1,6,7,
  10. Heikki Hyöty, MD, PHD1,8,
  11. Mikael Knip, MD, PHD1,4,9 and
  12. Olli Simell, MD, PHD1,2
  1. 1JDRF Center for Prevention of Type 1 Diabetes in Finland
  2. Departments of 2Pediatrics and
  3. 3Medical Microbiology, University of Turku, Turku, Finland
  4. 4Pediatric Research Center, Medical School, University of Tampere, and Department of Pediatrics, Tampere University Hospital, Tampere, Finland
  5. 5Department of Pediatrics, University of Oulu, Oulu, Finland
  6. 6Department of Clinical Microbiology, University of Kuopio, Kuopio, Finland
  7. 7Immunogenetics Laboratory, University of Turku, Turku, Finland
  8. 8Department of Virology, University of Tampere Medical School and Tampere University Hospital, Tampere, Finland
  9. 9Hospital for Children and Adolescents and Folkhälsan Research Institute, University of Helsinki, Helsinki, Finland


Objective- To compare the ages and sequence in which antibodies associated with type 1 diabetes and celiac disease appear and overt diseases develop in children with a HLA-conferred susceptibility to both diseases.

Research design and methods- We observed 2,052 children carrying genetic risk for both type 1 diabetes and celiac disease from birth until the median age of 5.7 years and analyzed diabetes- and celiac disease-associated antibodies in serum samples collected at 3- to 12-month intervals. Diabetes was confirmed by WHO criteria and celiac disease by duodenal biopsies.

Results- Altogether 342 children seroconverted to positivity for at least one diabetes-associated autoantibody and 88 to positivity for at least one celiac disease-associated antibody at the median ages of 3.0 and 1.5 years, respectively (P < 0.001). If only children with biochemically defined diabetes-associated autoantibodies against insulin, glutamic acid decarboxylase or IA-2A protein (n=146), and children with tissue transglutaminase autoantibodies were compared (n = 86), the median seroconversion ages were 2.5 and 3.0 years (P = 0.011). Fifty-one children progressed to overt diabetes at 4.5 years and 44 children to celiac disease at 4.3 years (P = 0.257). Of the 19 children who developed both diabetes- and celiac disease-associated antibodies, three progressed both to diabetes and celiac disease.

Conclusions- Children with HLA-conferred susceptibility to type 1 diabetes and celiac disease develop celiac disease-associated antibodies mostly at a younger or the same age than diabetes-associated autoantibodies. Clinical diabetes and celiac disease are commonly diagnosed at the same median age.


    • Received July 3, 2009.
    • Accepted December 22, 2009.