Vitamin D Status, Vitamin D Receptor Polymorphisms, and Risk of Type 2 Diabetes
April 18, 2024
The Journal of Clinical Endocrinology and Metabolism
TAKE-HOME MESSAGE
- This study found that higher levels of serum 25-hydroxyvitamin D were linked with a lower risk of developing type 2 diabetes (T2D), particularly for individuals with normal blood sugar levels. The risk of developing T2D decreased with increasing 25-hydroxyvitamin D concentrations, especially below 50 nmol/L. The study also revealed that higher levels of 25-hydroxyvitamin D were associated with a lower risk of T2D across HbA1c levels, and vitamin D receptor polymorphisms had no impact on the risk of T2D.
- Evidence suggests that ensuring sufficient levels of vitamin D in the body could be beneficial in preventing T2D in individuals with normal glucose regulation as well as in those with prediabetes.
Vitamin D levels and risk of diabetes
A good amount of research has correlated low vitamin D levels with the risk of metabolic dysfunction. In 2023, a systematic review and meta-analysis of three large studies showed that vitamin D supplementation to a level close to 50 ng/L in individuals with prediabetes reduced the risk of developing diabetes by 15% compared with that in individuals with prediabetes who did not supplement with vitamin D.1
However, this study of the UK Biobank data did not examine vitamin D supplementation. It focused on examining baseline vitamin D levels in individuals with normal blood glucose and those with prediabetes. The mainly White British cohort was followed for a median of 14 years to determine who would develop diabetes. The researchers also correlated vitamin D levels to vitamin D receptor genetic variants to determine whether the latter played a role in modifying the risk.
The findings showed that there was a correlation between low vitamin D levels and the risk of progression to diabetes among both individuals with normal blood sugar and prediabetes at baseline. The serum level that was the transition point from risk to protection was 50 nmol/L.
Please note that serum levels are measured in both nmol/L and ng/mL; 1.0 nmol/L = 0.4 ng/mL. Most of the world uses nmol/L but the United States uses ng/mL. Generally, vitamin D deficiency is considered as a level <50 nmol/L, which is equal to (50 x 0.4) 20 ng/mL. The therapeutic goal in replacing vitamin D is 120 nmol/L or about 50 ng/mL (120 x 0.4 = 48).
Individuals with vitamin D receptor genetic polymorphisms did not show a consistent trend. However, those with a T allele on the BsmI gene for the vitamin D receptor had a reduced risk of developing diabetes with high vitamin D levels. We may find out that genetic variants of the vitamin D receptor influence risk in the future, but it is too early to tell.
Lipid levels were also correlated. The highest association with the incidence of diabetes correlated with triglycerides. If an individual had both low vitamin D and high triglyceride levels, the risk of developing diabetes was elevated compared with having each alone.
Vitamin D is more a hormone than a vitamin and has been found to upregulate insulin sensitivity and improve pancreatic beta-cell function. We now have supporting evidence that low serum levels are associated with a higher risk of developing diabetes in the future among individuals with normal glucose and prediabetes at baseline.
Consider checking vitamin D levels and supplementing to bring serum levels to the mid-normal range (120 nmol/L or 50 ng/mL) in individuals at risk of metabolic dysfunction. And, remember, this study was in White Brits. The risk is higher among individuals with more pigment, particularly if they have moved away from the strong sun rays at the equator.
Reference
Abstract
CONTEXT
Vitamin D status has been associated with risk of type 2 diabetes (T2D), but evidence is scarce regarding whether such relation differs by glycemic status.
OBJECTIVE
To prospectively investigate the association between serum 25-hydroxyvitamin D [25(OH)D] and risk of incident T2D across the glycemic spectrum and the modification effect of genetic variants in vitamin D receptor (VDR).
METHODS
This prospective study included 379,699 participants without T2D at baseline from the UK Biobank. Analyses were performed according to glycemic status and HbA1c levels. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% CIs.
RESULTS
During a median of 14.1 years of follow-up, 6,315 participants with normoglycemia and 9,085 prediabetes patients developed T2D. Compared to individuals with 25(OH)D <25 nmol/L, the multivariable-adjusted hazard ratios (95% CIs) of incident T2D for those with 25(OH)D ≥75 nmol/L was 0.62 (0.56, 0.70) among the normoglycemia and 0.64 (0.58, 0.70) among the prediabetes. A significant interaction was observed between 25(OH)D and VDR polymorphisms among participants with prediabetes (Pinteraction=0.017), whereby the reduced HR of T2D associated with higher 25(OH)D was more prominent in those carrying T allele of rs1544410. Triglycerides levels mediated 26% and 34% of the association between serum 25(OH)D and incident T2D among participants with normoglycemia and prediabetes.
CONCLUSIONS
Higher serum 25(OH)D concentrations were associated with lower T2D risk across the glycemic spectrum below the threshold for diabetes, and the relations in prediabetes were modified by VDR polymorphisms. Improving lipid profile, mainly triglycerides, accounted for part of the favorable associations.
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Journal Reference