Background

Inorganic arsenic exposure and inter-individual differences in its metabolism have been associated with cardiometabolic risk. A more efficient arsenic metabolism profile (lower MMA%, higher DMA%) has been associated with reduced risk for arsenic-related health outcomes; however, this profile has also been associated with increased risk for diabetes-related outcomes. The mechanism behind these contrasting associations is equivocal; we hypothesized one carbon metabolism (OCM) may play a role.

Methods

We evaluated the association between OCM-related variables (nutrient intake and genetic variants) and both arsenic metabolism biomarkers (iAs%, MMA% and DMA%) and diabetes-related outcomes (metabolic syndrome, diabetes, HOMA2-IR and waist circumference) in 935 participants free of prevalent diabetes and metabolic syndrome from the Strong Heart Family Study, a family-based prospective cohort comprised of American Indian tribal members aged 14+ years.

Results

Of the 935 participants free of both diabetes and metabolic syndrome at baseline, 279 (29.8%) developed metabolic syndrome over a median of 5.3 years of follow-up and of the 1458 participants free of diabetes at baseline, 167 (11.3%) developed diabetes over follow-up. OCM nutrients were not associated with arsenic metabolism, however, higher vitamin B₆ was associated with diabetes-related outcomes (higher HOMA2-IR and increased risk for diabetes and metabolic syndrome). A polymorphism in an OCM-related gene, methionine synthase (MTR), was associated with both higher MMA% (β = 2.57, 95% CI: 0.22, 4.92) and lower HOMA2-IR (GMR = 0.79, 95% CI = 0.66, 0.93 per 5 years of follow-up). Adjustment for OCM variables did not affect previously reported associations between arsenic metabolism and diabetes-related outcomes; however, the association between the MTR variant and diabetes-related outcomes were attenuated after adjustment for arsenic metabolism.

Conclusions

Our findings suggest MMA% may be a partial mediator in the association between OCM and diabetes-related outcomes. Additional mediation analyses with longer follow-up period are needed to confirm this finding. Further research is needed to determine whether excess B vitamin intake is associated with increased risk for diabetes-related outcomes.

中文翻译：

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强心家庭研究中的砷，一种碳代谢与糖尿病相关的结果

背景

无机砷暴露及其个体间代谢差异与心脏代谢风险有关。更高效率的砷代谢特性（较低的MMA％，较高的DMA％）与降低与砷有关的健康结果的风险有关；但是，这种情况也与糖尿病相关结局的风险增加有关。这些相互关联的协会背后的机制是模棱两可的。我们假设一种碳代谢（OCM）可能起作用。

方法

我们评估了OCM相关变量（营养摄入和遗传变异）与砷代谢生物标志物（iAs％，MMA％和DMA％）和糖尿病相关结局（代谢综合征，糖尿病，HOMA2-IR和腰围）之间的关联。来自“强心家庭研究”的935名参与者没有普遍的糖尿病和代谢综合征，该研究是一个基于家庭的前瞻性队列，由14岁以上的美国印第安部落成员组成。

结果

在基线时无糖尿病和代谢综合症的935名参与者中，有279名（29.8％）在中位5.3年的随访中发展为代谢综合征，在基线时无糖尿病的1458名参与者中，有167名（11.3％）患有糖尿病过度跟进。OCM营养素与砷代谢无关，但是，较高的维生素B ₆与糖尿病相关的预后相关（较高的HOMA2-IR以及增加患糖尿病和代谢综合征的风险）。OCM相关基因蛋氨酸合酶（ MTR）的多态性）与较高的MMA％（β= 2.57，95％CI：0.22，4.92）和较低的HOMA2-IR（GMR = 0.79，95％CI = 0.66，0.93每5年随访）相关。对OCM变量的调整不会影响先前报道的砷代谢与糖尿病相关结局之间的关联。然而，调整砷代谢后，MTR变异与糖尿病相关结局之间的联系减弱了。

结论

我们的研究结果表明MMA％可能是OCM与糖尿病相关结局之间的部分介体。需要更多的随访时间较长的调解分析来确认这一发现。需要进行进一步的研究以确定过量摄入B族维生素是否与糖尿病相关结局的风险增加相关。