Cholecalciferol supplementation improves suppressive capacity of regulatory T-cells in young patients with new-onset type 1 diabetes mellitus — A randomized clinical trial

Treiber, Gerlies; Prietl, Barbara; Fröhlich‐Reiterer, Elke; Lechner, Evelyne; Ribitsch, Anja; Fritsch, Maria; Rami-Merhar, Birgit; Steigleder‐Schweiger, Claudia; Graninger, Winfried; Borkenstein, Martin; Pieber, Thomas R.

doi:10.1016/j.clim.2015.08.002

Cited by 87 publications

(92 citation statements)

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“…Its efficacy for preservation of RBCF was well demonstrated in previous studies [3,4,11]. The use of calcitriol was limited by the low dosages required to avoid adverse effects, which probably resulted in smaller effect sizes [6,7,10].…”

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confidence: 86%

“…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].…”

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confidence: 98%

“…Studies involving longer duration of supplementation detected a larger protective effect [3,4] as compared with shorter studies [8,11]. Other important factors in future studies are tighter glycaemic control during supplementation period, quantification of sunlight exposure and inclusion of T-cell parameters, which help to explain the molecular mechanisms of vitamin D action in the recruited patient population [2].…”

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confidence: 98%

“…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].…”

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confidence: 99%

“…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].…”

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confidence: 99%

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

Dayal

2016

Drugs

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The leading article by Ludvigsson in a recent issue of Drugs made for an interesting read [1]. It is an excellent review on the progress made in a fascinating field of treatment of b-cell disease in type 1 diabetes mellitus (T1D). The article aptly emphasises the need for preservation of residual b-cell function (RBCF) for important clinical benefits, elaborately examines the numerous immune and other interventions that have been tried over the past several decades in a bid to slow, halt or reverse the process of b-cell destruction, and discusses possible reasons for the failure of most single-agent interventions, the lessons learnt from each of these interventions, and the rather slow realisation by the scientific community that T1D is a heterogeneous disorder within and between patient populations that requires strict patient selection for particular interventions. Finally, the author makes a strong case for combination approaches aimed at treatment of bcell disease before or after onset of clinical disease, rightly accepting the risks and adverse events related to combined approaches by an interesting comparison of morbidity and mortality of T1D with respect to childhood cancers. While the article is comprehensive, I feel that the inclusion of recent information on vitamin D as an effective immunomodulator in T1D and a potential arm of future combination therapies to preserve b-cell function would have made the review complete in all respects.Vitamin D supplementation in T1D has received wide attention in recent years due partly to the growing epidemiological evidence of association of vitamin D deficiency (VDD) with T1D, and largely to the elucidation of underlying mechanisms of how it modulates the process of b-cell destruction [1,2]. 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]. In this regard, vitamin D may be included as a Tregs-boosting agent in combination therapies for b-cell disease [2]. Easy availability, low cost of therapy and relatively lower toxicity as compared with other immune interventions make vitamin D a suitable component of combined therapies. 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 dec...

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confidence: 86%

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confidence: 98%