03 Oct Vitamin D: No Causal Link With Type 2 Diabetes

MedicalResearch.com Interview with:
Dr Nita Forouhi, MRCP, PhD, FFPHM
Lead Scientist and Programme Leader
MRC Programme Leader and Consultant Public Health Physician
MRC Epidemiology Unit
University of Cambridge School of Clinical Medicine
Cambridge Biomedical Campus Cambridge, UK

Medical Research: What are the main findings of the study?

Dr. Forouhi: This large study found that low blood concentrations of 25-hydroxyvitamin D [25(OH)D], a clinical indicator of vitamin D status, were associated with an increased risk of type 2 diabetes, but this did not appear to be a cause-effect relationship. To investigate these associations, we did two things. We first did a systematic review and meta-analysis across 22 published studies and confirmed that there was a strong inverse relation between vitamin D levels and the risk of future new-onset type 2 diabetes among people who did not initially have diabetes. We then used a genetic approach, called Mendelian randomisation, which allows us to test a cause-effect relationship, and found that genetically lower vitamin D levels were not related to risk of type 2 diabetes. This means that we were able to distinguish between association and causation, and concluded that the vitamin D levels did not have a causal link with type 2 diabetes.

Medical Research: What was most surprising about the results?

Dr. Forouhi: Many health claims have been made for vitamin D, which has been described as a “wonder vitamin”or a “miracle cure” because of its possible benefits for several health outcomes including bone disease, immune-related conditions, cardiovascular disease, and type 2 diabetes. For type 2 diabetes we have found in this research that there is no convincing causal link with vitamin D levels.

This is in contrast to expectation because past studies that are observational in nature have shown that low circulating 25(OH)D concentrations are associated with an increased risk of type 2 diabetes. But such studies can be prone to limitations such as reverse causation and inadequate control for factors that can distort the true findings (known as confounding factors). Our study found that genetically predicted low concentrations of 25(OH)D, which are not subject to these limitations, were not associated with risk of type 2 diabetes. This suggests that the observed association is not likely to be causal in nature.

Medical Research: What should clinicians and patients take away from your report?

Dr. Forouhi: Our findings suggest that interventions to increase 25(OH)D concentrations such as through vitamin D supplementation might not reduce the risk of type 2 diabetes. Our current findings from the genetic approaches (using Mendelian randomisation) are consistent with the null findings from clinical trials where vitamin D supplementation was unrelated to development of type 2 diabetes or to intermediate markers of metabolic risk such as glucose or insulin levels or insulin resistance. While the role of vitamin D for bone health is well established from other work, we found no support for its role in the prevention of type 2 diabetes. On the other hand, we do have high quality research evidence showing that the maintenance of a healthy weight and healthy lifestyles including a healthy diet and physical activity are the main ways to prevent the onset of type 2 diabetes.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Forouhi: The findings of our study should stimulate further research in a number of areas to better understand the discrepancy between the observational evidence that shows an inverse association between vitamin D levels and type 2 diabetes and the null association when genetic approaches are used to test a causal link. For example, future research should account more rigorously for physical activity, as time spent in outdoor activity with sunshine exposure boosts the synthesis of vitamin D by the body but is also related to reducing the risk of type 2 diabetes. Most studies thus far have measured physical activity by self-report from study participants, and this can be quite inaccurate. There are now tools available for better measurement of physical activity, and these can help in teasing out the role of physical activity in the relationship between vitamin D levels and type 2 diabetes. Many other areas of research should be advanced, such as examining the role of more detailed adiposity and body fat measures, levels of other vitamin D metabolites besides the single metabolite (25(OH)D) thus far studied by us and others, and physiological processes such as liver function which can all affect vitamin D levels and risk of diabetes. Improved genetic approaches can also be applied with even larger sample sizes and the use of more genetic markers related to vitamin D levels. There is also the need for better clinical trials that are specifically designed to test the link between vitamin D and type 2 diabetes, with adequate dose and long duration of follow-up. The good news is that some such trials are currently underway and should yield helpful results to increase our understanding.

Citation:

Zheng Ye PhD,Stephen J Sharp MSc,Stephen Burgess PhD,Robert A Scott PhD,Fumiaki Imamura PhD,InterAct Consortium ,Claudia Langenberg PhD,Prof Nicholas J Wareham FRCP,Dr Nita G Forouhi FFPHM
The Lancet Diabetes & Endocrinology – 1 October 2014
DOI: 10.1016/S2213-8587(14)70184-6

Last Updated on October 3, 2014 by Marie Benz MD FAAD