维生素D干预对农村地区糖尿病前期人群的作用及机制研究

Type 2 diabetes mellitus (T2DM) has become a serious public health problem worldwide and look for the effective prevention measures is the focus of the scientific researchers. Previous studies suggested that vitamin D can promote the secretion of insulin and improve in insulin resistance, people with vitamin D deficiency may increase the risk of developing T2DM. However, there are few clinical intervention studies of whether vitamin D supplement could prevent T2DM, and the result is not yet clear. Based on the “cohort study in rural areas of Henan province”, this study screened out 594 cases from 2667 pre-diabetes mellitus population, to confirm the effect of vitamin D supplement on the pre-diabetes mellitus people by the randomized controlled clinical trials. The control group will be given placebo, the case group will be given vitamin D and vitamin D combined with calcium capsules for oral intervention lasted for 6 months. The effect of vitamin D in pre-diabetes mellitus and the impact of long-term diabetes conversion rate were observed with the fasting blood glucose and insulin resistance index as the outcome variables. Simultaneously, a rat model of T2DM was established to investigate the mechanism of vitamin D affecting T2DM by NF-κB pathway, which provide a scientific basis for the prevention and treatment of T2DM.

2型糖尿病已经成为严重的全球性公共卫生问题，寻找有效的防治措施是目前研究者关注的重点。既往研究显示维生素D能够促进胰岛素分泌、改善胰岛素抵抗，维生素D缺乏可能增加2型糖尿病发病风险。但补充维生素D对防治糖尿病的人群干预研究较少，结果尚不明确。本研究拟在“河南农村地区队列研究”基础上，从2667例糖尿病前期人群中筛选出594例作为研究对象，采用临床随机对照研究，用维生素D和维生素D联合钙胶囊进行口服干预6个月，以空腹血糖和胰岛素抵抗指数为结局变量，观察维生素D对糖尿病前期患者的作用及远期糖尿病转化率的影响。同时建立2型糖尿病大鼠模型，探讨维生素D通过NF-κB通路影响糖尿病的发病机制，为糖尿病的防治提供科学依据。

糖尿病前期是介于正常血糖和糖尿病（Diabetes mellitus，DM）之间的一种状态，是糖尿病防控的关键期。对糖尿病前期人群进行早期干预，可使2型糖尿病（Type 2 diabetes mellitus，T2DM）的发生风险降低40-70%。维生素D作为一种人体必需的脂溶性维生素，具有广泛的生物学活性，其与糖尿病发生发展的关系已成为当前医学研究热点之一。本研究在中国人群中开展随机对照试验，评价维生素D3对糖尿病前期人群胰岛β细胞功能的改善作用，同时联合动物实验，以内质网应激（Endoplasmic reticulum stress，ERS）为切入点，深入探索维生素D3调节胰岛β细胞功能的可能机制。研究发现，对糖尿病前期人群进行维生素D3干预，可有效逆转维生素D缺乏状况，调节脂质代谢；与钙联用时，可使胰岛素分泌增加，特别是在维生素D不足/缺乏人群中，胰岛β细胞功能改善效果显著。动物实验结果显示，维生素D可能通过抑制ERS诱导的细胞凋亡来保护胰岛功能。该研究阐明了维生素D补充在改善β细胞功能中的重要作用，为维生素D预防和治疗糖尿病提供了数据支持和科学参考。