Negativation of Type 1 Diabetes-Associated Autoantibodies to Glutamic Acid Decarboxylase and Insulin in Children Treated With Oral Calcitriol

J Diabetes. 2013 Sep;5(3):344-8. doi: 10.1111/1753-0407.12023. Epub 2013 May 29.

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.

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.

Publication types

  • Clinical Trial

MeSH terms

  • Administration, Oral
  • Adolescent
  • Autoantibodies / blood
  • Autoantibodies / immunology*
  • Calcitriol / administration & dosage
  • Calcitriol / therapeutic use*
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / diagnosis
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 1 / prevention & control*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Follow-Up Studies
  • Glutamate Decarboxylase / immunology*
  • Humans
  • Infant
  • Insulin / immunology*
  • Male
  • Prospective Studies
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • Vitamins / administration & dosage
  • Vitamins / therapeutic use

Substances

  • Autoantibodies
  • Insulin
  • Vitamins
  • Glutamate Decarboxylase
  • Calcitriol