Objective

Studies have shown that individual trace element levels might be associated with abnormal glycemic status, with implications for diabetes. Few studies have considered these trace elements as a mixture and their impact on gestational glucose levels. Comparing three statistical approaches, we assessed the associations between essential trace elements mixture and gestational glucose levels.

Methods

We used data from 1720 women enrolled in the Eunice Kennedy Shriver National Institute of Child Health and Human Development's Fetal Growth Study, for whom trace element concentrations (zinc, selenium, copper, molybdenum) were measured by inductively coupled plasma mass spectrometry (ICP-MS) using plasma collected during the 1st trimester. Non-fasting glucose levels were measured during the gestational diabetes mellitus (GDM) screening test in the 2nd trimester. We applied (1) Bayesian Kernel Machine Regression (BKMR); (2) adaptive Least Absolute Shrinkage and Selection Operator (LASSO) in a mutually adjusted linear regression model; and (3) generalized additive models (GAMs) to evaluate the joint associations between trace elements mixture and glucose levels adjusting for potential confounders.

Results

Using BKMR, we observed a mean 2.7 mg/dL higher glucose level for each interquartile increase of plasma copper (95% credible interval: 0.9, 4.5). The positive association between plasma copper and glucose levels was more pronounced at higher quartiles of zinc. Similar associations were detected using adaptive LASSO and GAM. In addition, results from adaptive LASSO and GAM suggested a super-additive interaction between molybdenum and selenium (both p-values = 0.04).

Conclusion

Employing different statistical methods, we found consistent evidence of higher gestational glucose levels associated with higher copper and potential synergism between zinc and copper on glucose levels.

中文翻译：

---

评估妊娠早期微量元素混合物与孕中期妊娠葡萄糖水平之间的关联：三种统计方法的比较。

客观的

研究表明，个别微量元素水平可能与异常的血糖状况有关，并可能影响糖尿病。很少有研究认为这些微量元素是混合物，它们对妊娠葡萄糖水平的影响。比较三种统计方法，我们评估了必需微量元素混合物与妊娠葡萄糖水平之间的关联。

方法

我们使用了来自Eunice Kennedy Shriver国家儿童健康与人类发展研究所胎儿生长研究的1720名妇女的数据，通过电感耦合等离子体质谱法（ICP-MS）测量了其中的痕量元素浓度（锌，硒，铜，钼）。 ）使用第三个月收集的血浆。在妊娠中期的妊娠糖尿病（GDM）筛查测试中测量了非空腹血糖水平。我们应用了（1）贝叶斯内核机器回归（BKMR）；（2）在相互调整的线性回归模型中的自适应最小绝对收缩和选择算子（LASSO）；（3）通用添加剂模型（GAM），用于评估微量元素混合物和葡萄糖水平之间的联合关联性，以调节潜在的混杂因素。

结果

使用BKMR，我们观察到血浆铜每四分位数的增加平均增加2.7 mg / dL葡萄糖水平（95％可信区间：0.9、4.5）。在较高的锌四分位数中，血浆铜和葡萄糖水平之间的正相关性更加明显。使用自适应LASSO和GAM检测到相似的关联。此外，自适应LASSO和GAM的结果表明，钼和硒之间存在超加性相互作用（p值均为0.04）。

结论

采用不同的统计方法，我们发现与较高的铜有关的妊娠葡萄糖水平较高的一致证据，以及锌与铜之间对葡萄糖水平的潜在协同作用。