Association Between Type 1, Type 2 Cytokines, Diabetic Autoantibodies and 25-hydroxyvitamin D in Children With Type 1 Diabetes

J Endocrinol Invest. 2016 Dec;39(12):1425-1434. doi: 10.1007/s40618-016-0514-9. Epub 2016 Aug 19.


Purpose: Vitamin D may play a role in the pathogenesis of type 1 diabetes (T1D). The aim of the current study was to determine the possible association between 25-hydroxyvitamin D [25(OH)D] levels and circulating levels of type 1 and type 2 cytokines, as well as the pathophysiology of T1D in children.

Methods: A total of 250 T1D patients and 250 sex- and age-matched T1D-free controls were screened for 25(OH)D, hemoglobin A1c (HbA1c), type 1 and type 2 cytokines, C-reactive protein (CRP) and bone mineral metabolism, as well as antibodies against insulin, glutamic acid decarboxylase (anti-GAD 65) and islet cells.

Results: Our data showed that the plasma level of 25(OH)D was significantly lower in T1D patients and that there was a significant negative correlation between 25(OH)D levels and HbA1c values. There was a significant association between deficient levels of 25(OH)D and higher levels of cytokines (IFN-γ, TNF-α, IL-6, IL-1β, IL-4 and IL-10) and CRP. Total blood hemoglobin, the hematocrit percentage, body mass index SDS values, phosphate and magnesium levels were significantly lower in T1D patients than in T1D-free subjects. The levels of parathyroid hormone and alkaline phosphatase were significantly higher in T1D patients. Higher levels of cytokines were significantly associated with deficient levels of 25(OH)D. Moreover, in T1D patients, higher levels of islet antibodies, anti-GAD antibodies and anti-insulin antibodies were significantly associated with deficient levels of 25(OH)D.

Conclusions: In type 1 diabetic children, deficient levels of 25(OH)D are associated with high levels of HbA1c, circulatory cytokines and antibody markers.

Keywords: Antibodies; Cytokines; Immunomodulation; Pathogenesis; Type 1 diabetes; Vitamin D.

MeSH terms

  • Autoantibodies / blood*
  • Biomarkers / blood*
  • Case-Control Studies
  • Child
  • Cross-Sectional Studies
  • Cytokines / blood*
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / physiopathology*
  • Female
  • Flow Cytometry
  • Humans
  • Immunomodulation
  • Male
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood


  • Autoantibodies
  • Biomarkers
  • Cytokines
  • Vitamin D
  • 25-hydroxyvitamin D