Serum vitamin D levels in relation to type-2 diabetes and prediabetes in adults: a systematic review and dose–response meta-analysis of epidemiologic studies

Background Findings of observational studies that investigated the relationship between vitamin D deficiency and abnormal glucose homeostasis were contradictory. This meta-analysis of epidemiologic studies evaluated the association of vitamin D status and risk of type-2 diabetes (T2D) and prediabetes in adults.Methods A systematic search was conducted on all published articles in five electronic databases (including MEDLINE/PubMed, EMBASE, Institute for Scientific Information, Scopus and Google scholar), up to August 2020. Twenty-eight prospective cohort and nested case-control studies and 83 cross-sectional and case-control investigations that reported relative risks (RRs) or odds ratios (ORs) with 95% confidence intervals (CIs) for abnormal glucose homeostasis in relation to serum vitamin D levels in adults were included in the analysis.Results In prospective studies, high versus low level of vitamin D was respectively associated with significant 35%, 30% and 51% decrease in risk of T2D (RR:0.65; 95%CI: 0.55–0.76; 27 effect sizes), combined T2D and pre-diabetes (RR:0.70; 95%CI: 0.52–0.95; 9 effect sizes) and pre-diabetes (RR:0.49; 95%CI: 0.26–0.93; 2 effect sizes). These inverse associations were significant in almost all subgroups. Dose–response analysis in prospective studies showed that each 10 ng/ml increase in serum vitamin D levels resulted in 12% and 11% reduced risk of T2D (RR:0.88; 95%CI: 0.83–0.94) and combined T2D and prediabetes (RR:0.89; 95%CI: 0.87–0.92), respectively. In cross-sectional and case-control studies, highest versus lowest level of serum vitamin D was linked to reduced odds of T2D (OR:0.64; 95%CI: 0.57–0.72; 42 effect sizes) and combined T2D and pre-diabetes (OR:0.79; 95%CI: 0.74–0.85; 59 effect sizes); but not pre-diabetes (OR:0.64; 95%CI: 0.17–2.37; 11 effect sizes).Conclusion This meta-analysis of epidemiologic studies disclosed that serum vitamin D level was reversely associated with the risk of T2D and combined T2D and prediabetes in adults, in a dose–response manner. However, the association was not remarkable for pre-diabetes.