title: T-lymphocyte and glycemic status after vitamin D treatment in type 1 diabetes: A randomized controlled trial with sequential crossover.
abstract: 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)D3increased 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.
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Medical Department 1, University Hospital, Goethe University, Frankfurt am Main, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Bogdanou
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Medical Department 1, University Hospital, Goethe University, Frankfurt am Main, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Penna-Martinez
authors.affiliation: Institute of Biostatistics and Mathematical Modeling, Goethe University Frankfurt, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Filmann
authors.affiliation: Institute of Biostatistics and Mathematical Modeling, Goethe University Frankfurt, Germany.
authors.forename: T L
authors.initials: TL
authors.lastname: Chung
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Medical Department 1, University Hospital, Goethe University, Frankfurt am Main, Germany.
authors.forename: Y
authors.initials: Y
authors.lastname: Moran-Auth
authors.affiliation: Pharmacy of the Goethe University Hospital, Frankfurt am Main, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Wehrle
authors.affiliation: Laboratory for Stem Cell Transplantation and Immunotherapy, Clinic for Pediatric and Adolescent Medicine, University Hospital Frankfurt, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Cappel
authors.affiliation: Laboratory for Stem Cell Transplantation and Immunotherapy, Clinic for Pediatric and Adolescent Medicine, University Hospital Frankfurt, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Huenecke
authors.affiliation: Institute of Biostatistics and Mathematical Modeling, Goethe University Frankfurt, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Herrmann
authors.affiliation: Institute of Cellular Therapeutics, Hanover Medical School, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Koehl
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Medical Department 1, University Hospital, Goethe University, Frankfurt am Main, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Badenhoop
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis; D001786:Blood Glucose / Q000032:analysis*; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014807:Vitamin D / Q000627:therapeutic use*; D014808:Vitamin D Deficiency / Q000188:drug therapy* / Q000209:etiology; D014815:Vitamins / Q000627:therapeutic use
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D014807:Vitamin D; D014815:Vitamins; C517652:hemoglobin A1c protein, human
keywords: T regulatory cells; cholecalciferol; glucometabolism; type 1 diabetes; vitamin D; vitamin D genotype