title: Negativation of type 1 diabetes-associated autoantibodies to glutamic acid decarboxylase and insulin in children treated with oral calcitriol.
abstract: BACKGROUND
  Based on recent knowledge of the possible involvement of 1,25-dihydroxyvitamin D in the pathogenesis of type 1 diabetes (T1D) and the results of its administration in animal models, we conducted a clinical trial by treating high-risk children, positive for T1D autoantibodies, with oral calcitriol.
  
  
  METHODS
  The present prospective trial was performed on 12 children (1.5-13 years old) who were investigated for the potential risk of T1D because of an already diagnosed association of celiac disease and autoimmune thyroiditis (four girls), autoimmune thyroiditis at a very young age (two girls, two boys), a diagnosis of T1D in siblings (two boys), and impaired glucose tolerance (IGT; one boy, one girl). Serum autoantibody levels, including islet cell autoantibodies, anti-glutamic acid decarboxylase (GAD) 65, insulin autoantibodies (IAA), and anti-tyrosine phosphatase, and markers of calcium metabolism were evaluated prior to and at 6-monthly intervals after the initiation of 0.25 μg/day calcitriol for 1-3 years.
  
  
  RESULTS
  In all children, persistent negativation of the anti-GAD65 antibodies and IAA was observed within 0.4-2.1 years. Of the two children with IGT, the boy proved to have maturity onset diabetes of the young (MODY) 2, whereas the glycemic profile was normalized in the girl.
  
  
  CONCLUSIONS
  Despite the small number of subjects and the absence of a control group in the present study, 0.25 μg/day calcitriol effectively negativates anti-GAD65 antibodies and IAA after a median time of 6 months. This simple, safe, and low-cost strategy may prove effective in the prevention of T1D in the future.
authors.affiliation: 3rd Department of Pediatrics, Attikon University Hospital, Athens, Greece. info@pedoendo.gr
authors.forename: Dimitrios T
authors.initials: DT
authors.lastname: Papadimitriou
authors.forename: Chrisanthi
authors.initials: C
authors.lastname: Marakaki
authors.forename: Andreas
authors.initials: A
authors.lastname: Fretzayas
authors.forename: Polyxeni
authors.initials: P
authors.lastname: Nicolaidou
authors.forename: Anastasios
authors.initials: A
authors.lastname: Papadimitriou
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D002117:Calcitriol / Q000008:administration & dosage / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis / Q000276:immunology* / Q000517:prevention & control*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006801:Humans; D007223:Infant; D007328:Insulin / Q000276:immunology*; D008297:Male; D011446:Prospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014815:Vitamins / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D001323:Autoantibodies; D007328:Insulin; D014815:Vitamins; D005968:Glutamate Decarboxylase; D002117:Calcitriol
keywords: anti-glutamic acid decarboxylase 65 antibody; calcitriol; insulin autoantibodies; prevention trial; type 1 diabetes; 抗谷氨酸脱羧酶65抗体，骨化三醇，胰岛素自身抗体，预防试验，1型糖尿病