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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.

Author information

1
Division of Endocrinology, Diabetes and Metabolism, Medical Department 1, University Hospital, Goethe University, Frankfurt am Main, Germany.
2
Institute of Biostatistics and Mathematical Modeling, Goethe University Frankfurt, Germany.
3
Pharmacy of the Goethe University Hospital, Frankfurt am Main, Germany.
4
Laboratory for Stem Cell Transplantation and Immunotherapy, Clinic for Pediatric and Adolescent Medicine, University Hospital Frankfurt, Germany.
5
Institute of Cellular Therapeutics, Hanover Medical School, Germany.

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.

KEYWORDS:

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

PMID:
27764529
DOI:
10.1002/dmrr.2865
[Indexed for MEDLINE]

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