Seasonal variability of vitamin D status in patients with inflammatory bowel disease – A retrospective cohort study

ObjectivesVitamin D deficiency predicts unfavorable disease outcomes in inflammatory bowel disease. Endogenous vitamin D synthesis is affected by seasonal factors including sunlight exposure, raising the question whether seasonality determines the risk of vitamin D deficiency and may mask other clinical risk factors.MethodsUnivariable and multiple regression analyses were performed in a retrospective cohort of 384 patients to determine risk factors for vitamin D deficiency. Since the observed 25-hydroxyvitamin D [25(OH)D] concentrations followed a sinusoidal pattern over the year, all 25(OH)D concentrations were normalized for the predicted variability of the respective day of analysis based on a sinusoidal regression analysis of 25(OH)D test results obtained in more than 86,000 control serum samples.ResultsVitamin D deficiency was highly prevalent in patients with Crohn’s disease or ulcerative colitis (63% and 55%, respectively) and associated with winter/spring seasons. After normalization of 25(OH)D concentrations for the day of analysis, vitamin D deficiency was associated with histories of complications related to inflammatory bowel disease, surgery, smoking and ongoing diarrhea while initial disease manifestation during adulthood, ongoing vitamin D supplementation and diagnosis of ulcerative colitis vs. Crohn’s disease appeared to be protective. Multiple regression analyses revealed that vitamin D deficiency was associated with disease activity in Crohn’s disease and anemia in ulcerative colitis patients. Only few deficient patients achieved sufficient 25(OH)D concentrations over time. However, increasing 25(OH)D concentrations correlated with improved Crohn’s disease activity.ConclusionsVitamin D deficiency was highly prevalent in patients with Crohn’s disease and ulcerative colitis and dependent on the season of the year. Following normalization for seasonality by sinusoidal regression analysis, vitamin D deficiency was found to be associated with parameters of complicated disease course while increasing 25(OH)D concentrations over time correlated with reduced activity of Crohn’s disease.【研究目的】维生素D缺乏可预测炎症性肠病（Inflammatory Bowel Disease, IBD）患者的不良疾病结局。内源性维生素D合成受日照等季节相关因素影响，由此提出疑问：季节节律是否会影响维生素D缺乏的发病风险，进而掩盖其他临床危险因素？ 【研究方法】本研究纳入384例患者的回顾性队列，通过单因素及多因素回归分析明确维生素D缺乏的危险因素。鉴于检测得到的25-羟维生素D [25(OH)D] 浓度全年呈现正弦波动模式，本研究基于对86000余份对照血清样本的25(OH)D检测结果开展正弦回归分析，针对检测当日的预测变异性对所有25(OH)D浓度进行标准化处理。 【研究结果】克罗恩病（Crohn’s Disease）与溃疡性结肠炎（Ulcerative Colitis）患者的维生素D缺乏患病率极高，分别达63%与55%，且与冬春季节显著相关。对检测当日的25(OH)D浓度完成标准化处理后，维生素D缺乏与炎症性肠病相关并发症病史、手术史、吸烟史及持续性腹泻呈正相关；而成年起病、持续维生素D补充治疗，以及诊断为溃疡性结肠炎而非克罗恩病则表现为保护因素。多因素回归分析显示，维生素D缺乏与克罗恩病患者的疾病活动度及溃疡性结肠炎患者的贫血状态显著相关。随访期间仅少数维生素D缺乏患者的25(OH)D浓度恢复至充足水平，但25(OH)D浓度的升高与克罗恩病患者疾病活动度的改善呈显著相关。 【研究结论】克罗恩病与溃疡性结肠炎患者的维生素D缺乏患病率极高，且与检测季节显著相关。通过正弦回归分析完成季节标准化后，维生素D缺乏与炎症性肠病的复杂病程参数显著相关；而随访期间25(OH)D浓度的升高则与克罗恩病患者疾病活动度的降低呈显著相关。