Spotlight on vitamin D

One study found more cardiovascular events in diabetic patients with vitamin D deficiency, while a trial found no effect of vitamin D supplements on cardiovascular biomarkers, and a genetic meta-analysis suggested that associations between vitamin D levels and diabetes are not causal.

Three recent studies looked at the relationship between vitamin D and diabetes.

Risk of cardiovascular events or death was lower in diabetes patients with higher serum vitamin D levels, found a study published by Diabetes Care on Nov. 8. It used National Health and Nutrition Examination Survey data on 6,329 adults with diabetes. According to a one-time serum level measurement, 46.6% were vitamin D-deficient (<50 nmol/L). Those with higher serum 25(OH)D levels had lower levels of glucose, insulin, HbA1c, blood lipids, and C-reactive protein and less insulin resistance. There was a significant, linear association between higher vitamin D levels and lower all-cause and cardiovascular mortality (hazard ratios with 25(OH)D <25 nmol/L vs. >75 nmol/L, 0.59 and 0.50, respectively). Cancer mortality trended the same way, but the difference was not statistically significant. The study authors said that the results “support the potential benefits of maintaining adequate vitamin D status in the prevention of premature death among individuals with diabetes” but noted that the observational study could not establish causality.

A secondary analysis of a randomized trial of vitamin D supplementation in patients with type 2 diabetes did not find any associated improvements in cardiovascular biomarkers, according to results published by Diabetologia on Oct. 24. The Vitamin D and Omega-3 Trial to Prevent and Treat Diabetic Kidney Disease randomized U.S. adults with type 2 diabetes and without known cardiovascular disease, malignancy, or end-stage kidney disease to vitamin D3, 2,000 IU/d, and n-3 fatty acids, 1 g/d (n=370); vitamin D and a placebo (n=333); n-3 fatty acids and a placebo (n=289); or two placebos (n=320). Their blood was sampled for serum IL-6, high-sensitivity C-reactive protein (hsCRP), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) at baseline and at two and five years. After five years, mean IL-6 and hsCRP levels were not significantly changed and mean NT-proBNP levels had increased, both compared to baseline and between patients who took vitamin D and those on placebo. The n-3 fatty acids were not associated with any change in the biomarkers. The results of this secondary analysis were consistent with those of the main trial, “which did not demonstrate a reduction in major cardiovascular events or invasive cancer with either intervention,” the authors said. “Our study contributes to a growing body of literature that suggests the observed benefits of vitamin D3 and n-3 fatty acids in laboratory studies may not directly translate to clinical benefit.”

Another study, published by PLOS Medicine on Oct. 16, looked at different vitamin D metabolites and their potential relationship with type 2 diabetes. The meta-analysis gathered genetic variants and measures of vitamin D levels in more than 40,000 people of European descent to look for observational or causal associations between vitamin D and type 2 diabetes. The results, which involved 20 genetic loci associated with vitamin D levels, showed discordant associations with type 2 diabetes risk. The authors concluded that these findings do not support a causal relationship between vitamin D and type 2 diabetes and provide an argument against the use of vitamin D supplementation for the prevention of diabetes. They noted that this null finding is consistent with a lack of benefit seen in recent trials of vitamin D supplementation. A limitation of the study is the lack of inclusion of patients of other ethnicities, making its generalizability uncertain.