Type 1 Diabetes and Vitamin D Revisited
Vitamin D is one of the "in vogue" vitamins in metabolic research, most specifically in diabetes. Vitamin D deficiency has been associated with hypertension, neoplasia, and both type 1 and type 2 diabetes. In a past blog I discussed the correlation of ultraviolet exposure and the development of type 1 diabetes. In that Diabetolgia paper, the authors of the study analyzed the relationship between ultraviolet B irradiance (the primary source of human Vitamin D) and age-standardized incidence rates of type 1 diabetes in children based on world location. The results of the study noted higher incidence rates in regions with higher northern and southern latitudes (including Finland, Sardinia, Italy, Aberdeen, UK, Prince Edward Island, Canada, Sweden, and Norway).
These rates were statistically significant (p<0.001). The authors concluded that there was an association between low Vitamin D exposure and high incidence rates of type 1 diabetes in children. Most interestingly, incidence levels approached zero in regions with high ultraviolet irradiance (vitamin D exposure).
Now there is additional evidenced-based data that Vitamin D Deficiency is associated with retinopathy in children and adolescents with type 1 diabetes. In this brief report published in Diabetes Care Volume 34, June 2011, 1400-1402, the authors (Kaur, Donaghue, Chan et. al) from New South Wales, Australia, researched the association of Vitamin D deficiency and the increased prevalence of the microvascular (retinopathy, nephropathy and peripheral nephropathy) complications in children and adolescence. (Macro vascular complications generally refer to cardiac disease.)
The study was cross-sectional including 517 patients aged 8-20 years of age. 25 Hydroxyvitamin D was measured. These children were followed in the outpatient clinic at The Children's Hospital at Westmead, in Westmead, Australia, between 2009 and 2010. This cohort represented one-third of children and adolescents in the state of New South Wales, Australia.
1. Retinopathy evaluated by seven-field stereoscopic retinal photography
2. Peripheral nephropathy was measured by thermal and vibration threshold testing
3. Nephropathy was determined by microalbuminuria.
What were the results?
1. Only retinopathy prevalence was higher in cases with Vitamin D deficiency (p=0.02).
2. Peripheral Neuropathy or Nephropathy was NOT associated with Vitamin D deficiency.
3. Lastly, using logistic regression, retinopathy was associated with Vitamin D
Deficiency, diabetes duration and hb A1c.
What can we infer from these results?
Perhaps our diabetes team should be measuring Vitamin D levels along with "routine" laboratory work, because it appears that Vitamin D deficiency may "have a permissive role" in the initial stages of retinopathy according to the authors of the study. The Vitamin D receptor is present in the human retina (I did not know this) and apparently gene variants (polymorphisms) of the Vitamin D receptor are related to retinopathy risk in type 1 diabetes. It would be interesting to note if these polymorphisms are present in children and adolescents living in different latitudes and if this particular Vitamin D Receptor polymorphism is more prevalent in northern and southern latitudes!
The authors found no relationship between ethnicity and retinopathy. (There was concern that lower Vitamin D is associated with darker skin pigmentation.)
Keep in mind that this is a cross-sectional study and therefore one cannot state that Vitamin D deficiency causes retinopathy. Generally, one can only prove causal relationships by blinded prospective studies (which would be difficult to do in this type of research). My suggestion is to check for Vitamin D levels annually, along with routine screening tests for the most commonly associated autoimmune diseases: thyroid (thyroid peroxidase antibodies initially and then yearly TSH levels), and celiac disease (serum tissue transglutaminase and IgA levels and if elevated, serum endomysial IgA antibodies). Of course, it is hoped that future studies will determine if Vitamin D plays a causal relationship to chronic diseases such as diabetes.