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

Abstract

To evaluate the effect of vitamin D 3 on cytokine levels, regulatory T cells, and residual ␤-cell function decline when cholecalciferol (vitamin D 3 administered therapeutically) is given as adjunctive therapy with insulin in new-onset type 1 diabetes mellitus (T1DM).

Levels of 25(OH)D3, IL-2, and C-peptide in Children with Type 1 Diabetes Mellitus (T1DM) Receiving Vitamin D3 Supplementation

“…The cumulative incidence of progression to undetectable fasting C-peptide level reached 18.7% in the cholecalciferol group and 62.5% in the placebo group. Therefore, cholecalciferol is safely used as an adjunctive therapy with insulin and is associated with protective immunological effects and a slow decline in the function of residual β -cells in patients with T1DM [30]. A study of patients aged 18 -39 years in Germany who was newly diagnosed with T1DM who received 0.25 µg 1.25(OH) 2 D 3 or placebo daily for 9 months and followed for a total of 18 months.…”

Comment on: “Therapies to Preserve β-Cell Function in Type 1 Diabetes”

“…The dose of cholecalciferol used should be such that is able to achieve optimal serum vitamin D concentrations (40-60 ng/mL) required to produce immunomodulatory effects. In previous studies, higher vitamin D concentrations ([60 ng/mL) were shown to increase the number as well as functions of Tregs [3,4]. Thus, the cholecalciferol dose of 2000 IU/day may need to be increased in future studies, particularly in certain patient populations [11].…”

“…In previous studies, the protective effects of vitamin D on RBCF were better in patients with higher C-peptide concentrations at inclusion [3,9] than in those with lower baseline C-peptide [6,7]. The dose of cholecalciferol used should be such that is able to achieve optimal serum vitamin D concentrations (40-60 ng/mL) required to produce immunomodulatory effects.…”

“…In addition to the several previously described mechanisms of its immunomodulation in T1D, recent evidence suggests that vitamin D increases the numbers as well as the functional capacity of regulatory T cells (Tregs), which are an important component of the process of b-cell destruction in T1D [3,4]. It is thought that the combined approaches for future evaluation will include an antigen-specific agent, effector T cell-depleting ormodulating drug, and a Tregs-promoting agent [5].…”

“…While a number of studies in animal models have shown promising effects of vitamin D on insulin secretion and insulin sensitivity, the results of clinical trials in patients with T1D have been far less impressive [2,5]. Of the eight clinical studies conducted over the past decade, including one in patients with adult-onset latent autoimmune diabetes (LADA), two showed no effect of vitamin D supplementation on RBCF [6,7], four showed a slower decline of RBCF [3,4,8,9], while two others showed a trend towards slower decline of RBCF that did not reach a statistical significance [10,11]. Nevertheless, many lessons have been learnt from these trials similar to the experience with other immune interventions in T1D [5].…”