Efficacy of Vitamin D Supplementation on Glycaemic Control in Individuals With Type 2 Diabetes

Vitamin D and Glucose Control

Vitamin D enhances insulin sensitivity, glucose metabolism, and the ability of pancreatic islet cells to produce insulin. Prior studies have shown that low vitamin D levels increase the risk of developing diabetes.¹

This systematic review and meta-analysis of 39 studies gathered evidence to determine whether replacing vitamin D in individuals with low levels results in improved glucose control. The results showed that vitamin D had the greatest effect in individuals with diabetes and obesity who had vitamin D deficiency and an HbA1c measurement of 8% or greater.

People with larger subcutaneous fat deposits have a higher risk of vitamin D deficiency. Think of the subcutaneous layer as a barrier for vitamin D transport from the skin into the bloodstream. Vitamin D is also stored in fat mass, with higher supplemental doses required to overcome this deposition. This study recommended 2000 IU or higher per day for individuals with obesity and diabetes for improved glucose control.

This study and other studies suggest that checking vitamin D levels and replacing deficient vitamin D, particularly in individuals with diabetes and obesity, can improve fasting blood sugar, HbA1c measurements, and insulin sensitivity.

Reference

1. Fu Y, Lu M, Zhang K, et al. Vitamin D status, Vitamin D Receptor Polymorphisms, and Risk of Type 2 Diabetes: A Prospective Cohort Study. J Clin Endocrinol Metab. 2024;109(9):2173-2181. https://doi.org/10.1210/clinem/dgae221

A meta-analysis of individual participant data from three trials on vitamin D and diabetes prevention showed that vitamin D reduced the risk of progression from prediabetes to diabetes by 15%.¹ Additionally, vitamin D increased the likelihood of regression from prediabetes to normal glucose regulation by up to 48%. Based on these findings, the 2024 Endocrine Society Clinical Practice Guideline on Vitamin D for the prevention of disease recommends vitamin D supplementation to reduce the risk of diabetes in adults with prediabetes.² However, it is unclear whether vitamin D has a therapeutic role once type 2 diabetes is established.

This meta-analysis included 39 randomized, placebo-controlled trials that reported on the effects of vitamin D interventions on glycemic outcomes in patients with type 2 diabetes. Most trials were short-term (12 to 24 weeks). The combined results showed statistically significant reductions in fasting glucose levels (0.49 mmol/L [approximately 9 mg/dL]), HbA1c levels (0.30%), and insulin resistance assessed using the Homeostasis Model Assessment for Insulin Resistance.

Meta-analyses can yield valuable and actionable insights if the included studies are sufficiently similar. In this analysis, the heterogeneity statistic (I²) was high across all outcomes, suggesting that the observed differences between studies are unlikely to be explained by chance alone. This raises concerns regarding the validity of combining these results in a meta-analysis. The authors attempted to address this issue through subgroup analyses; however, stratifying by mean values of continuous variables, such as 25(OH)D, BMI, and HbA1c levels, introduces the risk of ecological fallacy. These analyses rely on the mean value of each trial cohort rather than individual participant data. For instance, within each trial, approximately half of the participants fall below and half above the mean 25(OH)D level, resulting in a substantial overlap among subgroups based on the mean serum 25(OH)D level. Consequently, such subgroup analyses can be misleading and may lead to erroneous conclusions.

This meta-analysis highlights the challenges of evaluating the impact of vitamin D supplementation on glycemia in patients with established diabetes receiving pharmacotherapy. An ideal study would be a large, well-designed trial that controls for confounders such as diabetes medications and lifestyle factors; however, such a trial is unlikely to be conducted. Although the findings of this meta-analysis suggest a modest vitamin D benefit on glycemia and insulin resistance, these effects are relatively small, and they could be achieved by optimizing the diabetes therapies that patients are already on. The role of vitamin D is more relevant in those with prediabetes to lower the risk of progression to diabetes.

References

1. Pittas AG, Kawahara T, Jorde R, et al. Vitamin D and Risk for Type 2 Diabetes in People With Prediabetes : A Systematic Review and Meta-analysis of Individual Participant Data From 3 Randomized Clinical Trials. Ann Intern Med. 2023;176(3):355-363. https://www.acpjournals.org/doi/10.7326/M22-3018
2. Demay MB, Pittas AG, Bikle DD, et al. Vitamin D for the Prevention of Disease: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2024;109(8):1907-1947. https://academic.oup.com/jcem/article/109/8/1907/7685305