4.7 Article

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

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DIABETES CARE
卷 33, 期 4, 页码 774-779

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AMER DIABETES ASSOC
DOI: 10.2337/dc09-1217

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资金

  1. Juvenile Diabetes Research Foundation International [4-1999-731, 4-2001-435, 1-2006-896, 36-2008-925]
  2. Sigrid Juselius Foundation
  3. Academy of Finland
  4. Paivikki and Sakari Sohlberg Foundation
  5. Novo Nordisk Foundation
  6. Jalmari and Rauha Ahokas Foundation
  7. Foundation for Pediatric Research, Finland
  8. Foundation for Diabetes Research, Finland
  9. Signe and Ane Gyllenberg Foundation
  10. Turku University Foundation
  11. Celiac Disease Association, Finland

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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 an HLA-conferred susceptibility to both diseases. RESEARCH DESIGN AND METHODS - We observed 2,052 children carrying genetic risks 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 World Health Organization 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, GAD, 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, 3 progressed to both 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 age or the same age at which they develop diabetes-associated autoantibodies. Clinical diabetes and celiac disease are commonly diagnosed at the same median age.

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