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Diabetes Metab Res Rev. 2017 Mar;33(3). doi: 10.1002/dmrr.2865. Epub 2016 Dec 6.

T-lymphocyte and glycemic status after vitamin D treatment in type 1 diabetes: A randomized controlled trial with sequential crossover.

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Division of Endocrinology, Diabetes and Metabolism, Medical Department 1, University Hospital, Goethe University, Frankfurt am Main, Germany.
Institute of Biostatistics and Mathematical Modeling, Goethe University Frankfurt, Germany.
Pharmacy of the Goethe University Hospital, Frankfurt am Main, Germany.
Laboratory for Stem Cell Transplantation and Immunotherapy, Clinic for Pediatric and Adolescent Medicine, University Hospital Frankfurt, Germany.
Institute of Cellular Therapeutics, Hanover Medical School, Germany.



Type 1 diabetes mellitus (T1D) is mediated by autoaggressive T effector cells with an underlying regulatory T-cell (Treg) defect. Vitamin D deficiency is highly prevalent in T1D, which can aggravate immune dysfunction. High-dose vitamin D treatment may enhance Tregs and improve metabolism in T1D patients.


In a randomized double-blind placebo-controlled trial with crossover design, patients received either for 3 months cholecalciferol 4000 IU/d followed by 3 months placebo or the sequential alternative. Thirty-nine T1D patients (19 women and 20 men) completed the trial.


Primary outcome was a change of Tregs, secondary HbA1C, and insulin demand. Effects were evaluated based on intra-individual changes between treatment and placebo periods for outcome measures. Exploratory analyses included vitamin D system variant genotyping and C-peptide measurements. Median 25(OH)D3 increased to 38.8 ng/ml with males showing a significantly stronger increase (p = .003). T-lymphocyte profiles did not change significantly (p > 2); however, the intra-individual change of Tregs between males and females was different with a significantly stronger increase in men (p = .017), as well as between genotypes of the vitamin D receptor (Apa, Taq, and Bsm: genotypes aa, TT, and bb; p = .004-0.015). Insulin demands declined significantly (p = .003-.039) and HbA1C improved (p < .001). Random C-peptide levels were low but rising (median, 0.125 ng/ml; range, 0.02-0.3) in 6 patients. No toxicity was observed.


A daily vitamin D dose of 4000 IU for 3 months was well tolerated and enhanced Tregs in males. Glucometabolic control improved in all. Subsequent larger trials need to address ß-cell function and genotyping for individualized vitamin D doses.


T regulatory cells; cholecalciferol; glucometabolism; type 1 diabetes; vitamin D; vitamin D genotype

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