Abstract
Vitamin D deficiency is highly prevalent in Saudi Arabia despite abundant sunlight and remains a major public health concern. Emerging evidence suggests that vitamin D deficiency contributes to immune dysregulation, chronic inflammation, and adverse metabolic outcomes in patients with diabetes mellitus (DM). This systematic review aimed to evaluate the evidence on immunological alterations in diabetic patients and to examine the role of vitamin D in modulating immune responses, with a particular focus on the Saudi population. This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered in PROSPERO. A comprehensive search of MEDLINE, EMBASE, Scopus, and Web of Science was performed to identify studies published between January 2015 and December 2025. Eligible studies included observational, interventional, experimental, and review studies investigating immunological parameters in patients with type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), or gestational diabetes mellitus (GDM) in relation to vitamin D status, deficiency, or supplementation. Nineteen studies met the inclusion criteria. Vitamin D deficiency was highly prevalent among Saudi patients with diabetes, affecting approximately 50–85% of participants, and was consistently associated with poor glycemic control, elevated HbA1c, insulin resistance, and systemic inflammation. Deficiency was linked to altered inflammatory cytokines, including TNF-α, IL-6, IL-8, IL-10, and IL-29. Genetic studies identified vitamin D receptor (VDR) polymorphisms as contributors to increased susceptibility to diabetes and inflammatory complications. In T1DM, reduced CYP27B1 expression and altered microRNA profiles were associated with islet autoimmunity. Intervention studies demonstrated that vitamin D supplementation improved immune function and reduced inflammatory biomarkers. Vitamin D deficiency is strongly associated with immune dysregulation and metabolic dysfunction in diabetes. Routine screening and targeted vitamin D supplementation may represent effective strategies to reduce inflammation, improve immune function, and decrease diabetes-related complications in Saudi Arabia.

Key words: Vitamin D Deficiency, diabetes mellitus, immune response, Saudi Arabia.