高砷暴露与糖尿病有关,但在低-中等水平,证据是混合的。砷代谢,部分是基因控制的,可能依赖于某些B族维生素,在砷毒性中起作用。
我们评估了砷暴露和代谢与2型糖尿病和胰岛素抵抗的前瞻性关联。
我们纳入了1,838名没有糖尿病的美洲印第安人男性和女性(中位年龄,36y).砷暴露被评估为无机砷(iAs)的总和,单甲基arsonate(MMA),和二甲基氨酸盐(DMA)尿液浓度(ΣAs)。砷代谢通过iAs的比例进行评估,MMA,和DMA超过它们的总和(iA%,MMA%,和DMA%)。在基线和随访时测量胰岛素抵抗的稳态模型评估(HOMA2-IR)。在随访时评估糖尿病的发生率。
中位数ΣAs,iAs%,MMA%,DMA%为4.4μg/g肌酐,9.5%,14.4%,75.6%,分别。超过10327人年的随访,252名参与者患上了糖尿病。基线时HOMA2-IR中位数为1.5。在基线时没有糖尿病前期的参与者中,每四分位数间距增加一次,发生糖尿病的完全调整风险比[95%置信区间(CI)]为1.57(95%CI:1.18,2.08)。砷代谢与糖尿病发病无关。ΣAs在基线时与HOMA2-IR呈正相关,但在随访时与HOMA2-IR呈负相关。当iAs%或DMA%降低时,增加的MMA%与较低的HOMA2-IR相关。砷代谢与HOMA2-IR的关联因B族维生素摄入量和AS3MT基因变异而不同。
在没有基线糖尿病前期的参与者中,砷暴露与糖尿病相关。低MMA%是横断面的,并与较高的HOMA2-IR相关。需要研究以确认砷代谢与B族维生素和AS3MT变体对糖尿病风险的可能相互作用。https://doi.org/10.1289/EHP2566.
High arsenic exposure has been related to diabetes, but at low-moderate levels the evidence is mixed. Arsenic metabolism, which is partly genetically controlled and may rely on certain B vitamins, plays a role in arsenic toxicity.
We evaluated the prospective association of arsenic exposure and metabolism with type 2 diabetes and insulin resistance.
We included 1,838 American Indian men and women free of diabetes (median age, 36 y). Arsenic exposure was assessed as the sum of inorganic arsenic (iAs), monomethylarsonate (MMA), and dimethylarsinate (DMA) urine concentrations (ΣAs). Arsenic metabolism was evaluated by the proportions of iAs, MMA, and DMA over their sum (iAs%, MMA%, and DMA%). Homeostasis model assessment for insulin resistance (HOMA2-IR) was measured at baseline and follow-up visits. Incident diabetes was evaluated at follow-up.
Median ΣAs, iAs%, MMA%, and DMA% was 4.4 μg/g creatinine, 9.5%, 14.4%, and 75.6%, respectively. Over 10,327 person-years of follow-up, 252 participants developed diabetes. Median HOMA2-IR at baseline was 1.5. The fully adjusted hazard ratio [95% confidence interval (CI)] for incident diabetes per an interquartile range increase in ΣAs was 1.57 (95% CI: 1.18, 2.08) in participants without prediabetes at baseline. Arsenic metabolism was not associated with incident diabetes. ΣAs was positively associated with HOMA2-IR at baseline but negatively with HOMA2-IR at follow-up. Increased MMA% was associated with lower HOMA2-IR when either iAs% or DMA% decreased. The association of arsenic metabolism with HOMA2-IR differed by B-vitamin intake and AS3MT genetics variants.
Among participants without baseline prediabetes, arsenic exposure was associated with incident diabetes. Low MMA% was cross-sectional and prospectively associated with higher HOMA2-IR. Research is needed to confirm possible interactions of arsenic metabolism with B vitamins and AS3MT variants on diabetes risk. https://doi.org/10.1289/EHP2566.