Plasma 25-hydroxyvitamin D and its genetic determinants in relation to incident type 2 diabetes: a prospective case-cohort study
Plasma 25-hydroxyvitamin D and its genetic determinants in relation to incident type 2 diabetes: a prospective case-cohort study
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DOI：
10.1007/s10654-013-9844-5
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发表时间：
2013-09-01
影响因子：
13.6
通讯作者：
Kaaks, Rudolf
中科院分区：
文献类型：
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作者：
Buijsse, Brian;Boeing, Heiner;Kaaks, Rudolf
目前尚不清楚维生素D是否能降低2型糖尿病（T2D）的风险。在一项观察性研究中，我们评估了血浆25-羟基维生素D （25(OH)D）与T2D事件之间的前瞻性关联，并评估了是否与基因决定的25(OH)D升高有关。我们使用了欧洲癌症前瞻性调查德国分部的病例队列研究。从53088名参与者中，平均随访6.6年，我们确定了一个随机亚队列，包括2121名参与者（57%为女性）和1572例T2D病例。25(OH)D在从冷冻储存中提取的基线血浆样本中进行测量。亚队列患者的平均血浆25(OH)D为47.1（第5 -95百分位19.6-80.7）nmol/L。在控制年龄、性别、中心、采血季节、教育程度和生活方式后，随着25(OH)D血浆浓度的增加，T2D的危险降低（P线性趋势< 0.0001）。在调整BMI和腰围后，相关性变为非线性（P非线性< 0.0001），反向相关性仅限于25(OH)D浓度低于45 nmol/L的参与者（每5 nmol/L高25(OH)D的风险比为0.91,95% CI 0.84-0.98）。通过加权四个独立的单核苷酸多态性对25(OH)D的影响，一个预测基因决定血浆25(OH)D的评分解释了25(OH)D中3.7%的差异。遗传预测25(OH)D每升高5 nmol/L的风险比（95% CI）在整个研究样本中为0.98(0.89-1.08)，在25(OH)D < 45 nmol/L的子样本中为1.06（0.93-1.21）。后一项发现对25(OH)D与T2D的强烈因果关系提出了质疑，但需要进一步的大规模研究。
It is unclear whether vitamin D lowers risk of type 2 diabetes (T2D). In an observational study, we assessed the prospective association between plasma 25-hydroxyvitamin D (25(OH)D) and incident T2D, and evaluated whether it holds up for genetically determined elevated 25(OH)D. We used a case-cohort study nested within the German arm of the European Prospective Investigation into Cancer. From a total cohort of 53,088 participants with a mean follow-up of 6.6 years, we identified a random subcohort of 2,121 participants (57 % women) and 1,572 incident cases of T2D. 25(OH)D was measured in baseline plasma samples retrieved from frozen storage. Mean plasma 25(OH)D in the subcohort was 47.1 (5th-95th percentile 19.6-80.7) nmol/L. After controlling for age, sex, center, season of blood draw, education, and lifestyle, the hazard of T2D decreased across increasing plasma concentrations of 25(OH)D (P linear trend < 0.0001). The association became non-linear after adjustment for BMI and waist circumference (P non-linearity < 0.0001), with the inverse association being restricted to participants with 25(OH)D concentrations below similar to 45 nmol/L (hazard ratio per 5 nmol/L higher 25(OH)D 0.91, 95 % CI 0.84-0.98). A score predicting genetically determined plasma 25(OH)D by weighting four independent single-nucleotide polymorphisms by their effect on 25(OH)D, explained 3.7 % of the variance in 25(OH)D. The hazard ratio (95 % CI) per 5 nmol/L higher genetically predicted 25(OH)D was 0.98 (0.89-1.08) in the entire study sample and 1.06 (0.93-1.21) in the sub-sample with 25(OH)D < 45 nmol/L. This latter finding casts doubt on a strong causal association of 25(OH)D with T2D, but further research in large-scale consortia is needed.