Exploring the role of vitamin D in type 1 diabetes, rheumatoid arthritis and alzheimer's disease: new insights from accurate analysis of ten forms

Shah, Iltaf, Petroczi, Andrea and Naughton, Declan (2014) Exploring the role of vitamin D in type 1 diabetes, rheumatoid arthritis and alzheimer's disease: new insights from accurate analysis of ten forms. The Journal of Clinical Endocrinology & Metabolism, 99(3), ISSN (print) 0021-972X

Abstract

Context and objective: A comprehensive LC-MS/MS assay was developed to quantify 10 forms of vitamin D in sera from healthy adults and patients suffering from rheumatoid arthritis (RA), type 1 diabetes (T1-D) and Alzheimer's disease (AD). Design: The rapid assay, validated according to FDA guidelines with Chromsystem and DEQAS samples, was applied to 36 non-healthy sera samples (41.7% male, age range of 14–95, M = 54.00±21.98 years) consisting of individuals with RA, T1-D and AD (n=12 each); and was compared to samples from 32 healthy individuals (50% male, age range of 19–90, M = 58.83±22.93 years). Results: The key findings are: i) the 23R,25(OH)2D3 form was quantified for the first time (healthy = 0.427±0.633 nmol/L: combined disease = 0.395±0.483 nmol/L), ii) the 3-epi-25OHD3 metabolite was found in all groups with significantly higher concentration in the diseased samples (healthy = 6.093±6.711 nmol/L; combined disease 22.433±13.535 nmol/L, t(52.5)=-6.411; p<0.001), iii) a significant difference was found for the active form (1α25(OH)2D3) between health (0.027±0.035 nmol/L) and disease (0.433±0.870 nmol/L) (t(35.1)=-2.797: p=0.008), and iv) there was no significant correlation between the total circulating and total active forms in either disease or healthy group (r=-0.180 and −0.274, respectively, with no difference between the correlation coefficients, z=-0.389, p=0.697). ROC analysis showed good sensitivity and specificity for using 3-epi-25OHD concentration to predict disease status (AUC= 0.880, p < 0.001). Discriminant function analysis using concentrations of 23R,25(OH)2D3, 25OHD2 and 3-epi-25OHD classified 94.4% (91.7% in cross-validation) of the cases correctly. Conclusions: This study reveals significant differences between health and disease with epimers having the potential to relate to disease. The potential implications of the information gleaned from measuring all forms warrant application of more comprehensive assays for future clinical studies investigating the link between vitamin D and health.

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