Abstract and Introduction
Context: The effect of vitamin D supplementation on the risk of type 2 diabetes mellitus (T2DM) remains controversial because most randomized controlled trials (RCTs) have been small or have reported low doses of vitamin D.
Objective: To conduct a meta-analysis of RCTs testing vitamin D supplementation in the prevention of T2DM.
Data Sources: Database search of PubMed/MEDLINE, EMBASE, and the Cochrane Library was performed by 2 reviewers from inception through September 15, 2019.
Study Selection: We included RCTs that reported the effect of vitamin D supplementation for at least 1 year on T2DM prevention.
Data Extraction: Two independent reviewers extracted the data. The risk ratios (RRs) and 95% confidence intervals (CIs) were reported. Primary outcome of the meta-analysis was the incidence of T2DM.
Data Synthesis: Nine RCTs were included (43 559 participants). The mean age (standard deviation) was 63.5 (6.7) years. The RR for vitamin D compared with placebo was 0.96 (95% CI, 0.90–1.03); P = 0.30. In trials testing moderate to high doses of supplementation (≥1000 IU/day), all conducted among participants with prediabetes, the RR for vitamin D compared with placebo was 0.88 (95% CI, 0.79–0.99). In contrast, the trials testing lower doses, which were conducted in general population samples, showed no risk reduction (RR, 1.02; 95% CI, 0.94–1.10; P, interaction by dose = 0.04).
Conclusion: In patients with prediabetes, vitamin D supplementation at moderate to high doses (≥1000 IU/day), significantly reduced the incidence risk of T2DM, compared with placebo.
Diabetes mellitus (DM) is an important public health problem, affecting more than 500 million persons worldwide. Patients who have abnormally elevated glucose levels but do not meet the criteria of DM can be classified as having impaired glucose tolerance, impaired fasting glucose, or abnormally high average blood glucose level as manifested by high hemoglobin A1c (HbA1c). In the United States, almost one-third of the population has impaired fasting glucose, impaired glucose tolerance, or elevated HbA1c and are at elevated risk of developing DM within 5 years.[2,3]
Several risk factors for type 2 DM (T2DM) and abnormal glucose metabolism have been identified, including obesity and low physical activity.[2,4] In the past 10 to 15 years, increasing data from large-scale observational studies have shown an association between low 25-hydroxyvitamin D levels and development of T2DM,[5,6] with vitamin D supplementation being proposed as a potential intervention to lower the incidence of T2DM. An association between low vitamin D blood levels and impaired insulin secretion and increased insulin resistance has led to the hypothesis that vitamin D supplementation may reduce the risk of developing T2DM.[8,9] A short-term experimental study suggested that vitamin D supplementation leads to an improvement in pancreatic beta cell functioning and marginally lowers patients' HbA1c. Furthermore, vitamin D supplementation decreased fasting blood glucose level and HbA1c in patients with DM in some studies but not others. Clinical data remain unclear regarding the benefit of vitamin D supplementation in prevention of T2DM in patients already classified as prediabetic[13,14] or in those without glucose intolerance. Recently, several randomized controlled trials (RCTs) have evaluated whether vitamin D supplementation can reduce the incidence of T2DM, but most of these trials have been small or tested low doses of vitamin D. We therefore conducted a meta-analysis of RCTs of vitamin D supplementation in reducing the risk of T2DM.
J Clin Endocrinol Metab. 2020;105(8) © 2020 Endocrine Society