Influence of the vitamin D plasma level and vitamin D-related genetic polymorphisms on the immune status of patients with type 1 diabetes: a pilot study

Abstract

Vitamin D (VD) has been implicated in type 1 diabetes (T1D) by genetic and epidemiological studies. Individuals living in regions with low sunlight exposure have an increased T1D risk and VD supplementation reduced the risk in human individuals and mouse models. One possibility of how VD influences the pathogenesis of T1D is its immunomodulatory effect on dendritic cells (DC), which then preferentially activate regulatory T cells (T(regs) ). In the present pilot study, we collected blood samples from a small cohort of patients with T1D at baseline and months 6 and 12. VD-deficient patients were advised to supplement with 1000 IU/day VD. We found a considerable variation in the VD plasma level at baseline and follow-up. However, with higher VD plasma levels, a lower frequency of interleukin (IL)-4-producing CD8 T cells was observed. We further performed a comprehensive genotyping of 13 VD-related polymorphisms and found an association between VD plasma level and the genotype of the VD binding protein (DBP). The frequency of DC and T cell subsets was variable in patients of all subgroups and in individual patients over time. Nevertheless, we found some significant associations, including the 1,25-dihydroxyvitamin D(3) hydroxylase (CYP27B1) genotype with the frequency of DC subtypes. In summary, our preliminary results indicate only a limited influence of the VD plasma level on the immune balance in patients with T1D. Nevertheless, our pilot study provides a basis for a follow-up study with a larger cohort of patients.

T‐lymphocyte and glycemic status after vitamin D treatment in type 1 diabetes: A randomized controlled trial with sequential crossover

“…DNA was isolated from 2.5 ml of peripheral blood according to standard procedures and used for restriction fragment length polymorphism and real‐time polymerase chain reaction methods. Polymorphism positions are given according to the National Center for Biotechnology Information (http://www.ncbi.nlm.nih.gov).…”

“…We have shown in pilot studies in vitro and in vivo (using a daily dose of cholecalciferol 2000 IU/d) that both the cholecalciferol and the calcidiol VD compounds elicited differentiating effects on immunocytes of T1D patients with different genotype . This prompted us to perform a randomized clinical trial using a crossover design to study intraindividual VD effects with a daily dose of cholecalciferol 4000 IU/d.…”

Expression of Vitamin D Receptor (VDR) Positively Correlates with Survival of Urothelial Bladder Cancer Patients

“…In addition, vitamin D affects a broad range of cellular processes involved in the regulation of a variety of cellular functions including cell differentiation, DNA repair, apoptosis, metabolism, oxidative stress, and systemic body homeostasis [ 7 , 8 , 9 ]. Decreased vitamin D level, expression of the vitamin D receptor (VDR), and deregulation of the function of vitamin D-metabolizing enzymes are all related to serious diseases such as autoimmune diseases, neurologic disorders including schizophrenia, type 2 diabetes mellitus, increased mortality, multiple sclerosis, and others (reviewed in [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ]). There is a growing body of evidence that the biology of human cancers is affected by vitamin D body endocrine status (reviewed in [ 8 , 14 ]).…”

Effect of a Randomised Controlled Vitamin D Trial on Insulin Resistance and Glucose Metabolism in Patients with Type 2 Diabetes Mellitus

“…Hereby anti-infl ammatory eff ects may indirectly improve cardiovascular and metabolic health in patients with diabetes [ 38 ] . Since vitamin D's immune eff ects may vary between individuals with variants in their vitamin D system genotypes, intervention trials are needed to address pharmacogenomic diff erences for potential therapeutic stratification [ 41 ] . Our study shows a signifi cantly lower HbA1c with improving 25OHD status.…”