Effect of cholecalciferol as adjunctive therapy with insulin on protective immunologic profile and decline of residual β-cell function in new-onset type 1 diabetes mellitus

Arch Pediatr Adolesc Med. 2012 Jul 1;166(7):601-7. doi: 10.1001/archpediatrics.2012.164.


Objective: To evaluate the effect of vitamin D3 on cytokine levels, regulatory T cells, and residual β-cell function decline when cholecalciferol (vitamin D3 administered therapeutically) is given as adjunctive therapy with insulin in new-onset type 1 diabetes mellitus (T1DM).

Design and setting: An 18-month (March 10, 2006, to October 28, 2010) randomized, double-blind, placebo-controlled trial was conducted at the Diabetes Center of São Paulo Federal University, São Paulo, Brazil.

Participants: Thirty-eight patients with new-onset T1DM with fasting serum C-peptide levels greater than or equal to 0.6 ng/mL were randomly assigned to receive daily oral therapy of cholecalciferol, 2000 IU, or placebo.

Main outcome measure: Levels of proinflammatory and anti-inflammatory cytokines, chemokines, regulatory T cells, hemoglobin A1c, and C-peptide; body mass index; and insulin daily dose.

Results: Mean (SD) chemokine ligand 2 (monocyte chemoattractant protein 1) levels were significantly higher (184.6 [101.1] vs 121.4 [55.8] pg/mL) at 12 months, as well as the increase in regulatory T-cell percentage (4.55% [1.5%] vs 3.34% [1.8%]) with cholecalciferol vs placebo. The cumulative incidence of progression to undetectable (≤0.1 ng/mL) fasting C-peptide reached 18.7% in the cholecalciferol group and 62.5% in the placebo group; stimulated C-peptide reached 6.2% in the cholecalciferol group and 37.5% in the placebo group at 18 months. Body mass index, hemoglobin A1c level, and insulin requirements were similar between the 2 groups.

Conclusions: Cholecalciferol used as adjunctive therapy with insulin is safe and associated with a protective immunologic effect and slow decline of residual β-cell function in patients with new-onset T1DM. Cholecalciferol may be an interesting adjuvant in T1DM prevention trials.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age of Onset
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / physiology*
  • Body Mass Index
  • Brazil / epidemiology
  • C-Peptide / blood
  • Child
  • Cholecalciferol / administration & dosage*
  • Cytokines / blood
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 1 / epidemiology
  • Diabetes Mellitus, Type 1 / immunology
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Immunity, Cellular / drug effects*
  • Immunity, Cellular / immunology
  • Insulin / administration & dosage*
  • Male
  • Prevalence
  • Prospective Studies
  • Treatment Outcome
  • Vitamins / administration & dosage


  • C-Peptide
  • Cytokines
  • Hypoglycemic Agents
  • Insulin
  • Vitamins
  • Cholecalciferol