Influence of Vitamin D on Islet Autoimmunity and Beta-Cell Function in Type 1 Diabetes

Abstract

Type 1 diabetes (T1D) is a chronic autoimmune disease leading to immune-mediated destruction of pancreatic beta cells, resulting in the need for insulin therapy. The incidence of T1D is increasing worldwide, thus prompting researchers to investigate novel immunomodulatory strategies to halt autoimmunity and modify disease progression. T1D is considered as a multifactorial disease, in which genetic predisposition and environmental factors interact to promote the triggering of autoimmune responses against beta cells. Over the last decades, it has become clear that vitamin D exerts anti-inflammatory and immunomodulatory effects, apart from its well-established role in the regulation of calcium homeostasis and bone metabolism. Importantly, the global incidence of vitamin D deficiency is also dramatically increasing and epidemiologic evidence suggests an involvement of vitamin D deficiency in T1D pathogenesis. Polymorphisms in genes critical for vitamin D metabolism have also been shown to modulate the risk of T1D. Moreover, several studies have investigated the role of vitamin D (in different doses and formulations) as a potential adjuvant immunomodulatory therapy in patients with new-onset and established T1D. This review aims to present the current knowledge on the immunomodulatory effects of vitamin D and summarize the clinical interventional studies investigating its use for prevention or treatment of T1D.

Keywords: T1D; alfacalcidol; autoimmunity; calcidiol; calcitriol; cholecalciferol; honeymoon phase; immunotherapy; type 1 diabetes; vitamin D.

Figure 1

Chemical structure of the main forms of vitamin D and synthesis of biologically-active metabolites (1,25-dihydroxivitamin D2 and 1,25-dihydroxivitamin D3).

Figure 2

An overview of the anti-inflammatory and immunomodulatory effects exerted by the active metabolite of vitamin D 1,25(OH)2D3 (referred to as calcitriol) on innate and adaptive immune system. Red dots represent downregulation, whereas green dots represent upregulation. Abbreviations: IFN-γ, interferon gamma; IL-4, interleukin 4; IL-10, interleukin 10; IL-17, interleukin 17; IL-22, interleukin 22; M1, classically-activated macrophages; M2, alternatively-activated macrophages; MHC, major histocompatibility complex; TNF-α, tumor necrosis factor-alpha.