Abstract

Background:

Exposure to per- and polyfluoroalkyl substances (PFAS), a prevalent class of persistent pollutants, may increase the risk of type 2 diabetes.

Objective:

We examined associations between PFAS exposure and glucose metabolism in youth.

Methods:

Overweight/obese adolescents from the Study of Latino Adolescents at Risk of Type 2 Diabetes (SOLAR; $n=310$) participated in annual visits for an average of $3.3\pm 2.9\mathrm{y}$. Generalizability of findings were tested in young adults from the Southern California Children’s Health Study (CHS; $n=135$) who participated in a clinical visit with a similar protocol. At each visit, oral glucose tolerance tests were performed to estimate glucose metabolism and $\mathrm{\beta }\text{-cell}$ function via the insulinogenic index. Four PFAS were measured at baseline using liquid chromatography–high-resolution mass spectrometry; high levels were defined as concentrations $>66\text{th}$ percentile.

Results:

In females from the SOLAR, high perfluorohexane sulfonate (PFHxS) levels ($\ge 2.0\text{\hspace{0.17em}ng}/\mathrm{mL}$) were associated with the development of dysregulated glucose metabolism beginning in late puberty. The magnitude of these associations increased postpuberty and persisted through 18 years of age. For example, postpuberty, females with high PFHxS levels had $25\text{-mg}/\text{dL}$ higher 60-min glucose (95% CI: $12,39\mathrm{mg}/\text{dL}$; $p<0.0001$), $15\text{-mg}/\text{dL}$ higher 2-h glucose (95% CI: $1,28\mathrm{mg}/\text{dL}$; $p=0.04$), and 25% lower $\mathrm{\beta }\text{-cell}$ function ($p=0.02$) compared with females with low levels. Results were largely consistent in the CHS, where females with elevated PFHxS levels had $26\text{-mg}/\text{dL}$ higher 60-min glucose (95% CI: $6.0,46\mathrm{mg}/\text{dL}$; $p=0.01$) and $19\text{-mg}/\text{dL}$ higher 2-h glucose, which did not meet statistical significance (95% CI: $–1,39\mathrm{mg}/\text{dL}$; $p=0.08$). In males, no consistent associations between PFHxS and glucose metabolism were observed. No consistent associations were observed for other PFAS and glucose metabolism.

Discussion:

Youth exposure to PFHxS was associated with dysregulated glucose metabolism in females, which may be due to changes in $\mathrm{\beta }\text{-cell}$ function. These associations appeared during puberty and were most pronounced postpuberty. https://doi.org/10.1289/EHP9200

中文翻译：

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青少年暴露于全氟烷基物质和葡萄糖稳态

摘要

背景：

暴露于全氟和多氟烷基物质 (PFAS) 是一种普遍存在的持久性污染物，可能会增加患 2 型糖尿病的风险。

客观的：

我们检查了青年人 PFAS 暴露与葡萄糖代谢之间的关联。

方法：

来自有 2 型糖尿病风险的拉丁裔青少年研究 (SOLAR;$n=310$) 平均每年参与访问$3.3\pm 2.9\mathrm{是的}$. 南加州儿童健康研究 (CHS;$n=135$) 谁参加了具有类似协议的临床访问。在每次就诊时，进行口服葡萄糖耐量试验以估计葡萄糖代谢和$\mathrm{\beta }\text{-细胞}$通过胰岛素生成指数发挥作用。使用液相色谱-高分辨率质谱法在基线测量了四种 PFAS；高水平被定义为浓度$>66\text{th}$百分位。

结果：

在来自 SOLAR 的女性中，全氟己烷磺酸 (PFHxS) 水平较高 ($\ge 2.0\text{\hspace{0.17em}吴}/\mathrm{毫升}$) 与青春期后期开始的葡萄糖代谢失调的发展有关。这些关联的程度在青春期后增加并持续到 18 岁。例如，在青春期后，全氟己烷磺酸水平高的女性$25\text{-毫克}/\text{dL}$更高的 60 分钟葡萄糖（95% CI：$12,39\mathrm{毫克}/\text{dL}$;$p<0.0001$),$15\text{-毫克}/\text{dL}$更高的 2 小时葡萄糖（95% CI：$1,28\mathrm{毫克}/\text{dL}$;$p=0.04$)，并降低 25%$\mathrm{\beta }\text{-细胞}$功能 （$p=0.02$) 与低水平的女性相比。CHS 的结果基本一致，全氟己烷磺酸水平升高的女性$26\text{-毫克}/\text{dL}$更高的 60 分钟葡萄糖（95% CI：$6.0,46\mathrm{毫克}/\text{dL}$;$p=0.01$） 和$19\text{-毫克}/\text{dL}$较高的 2 小时血糖，不符合统计学意义（95% CI：$–1,39\mathrm{毫克}/\text{dL}$;$p=0.08$）。在男性中，没有观察到全氟己烷磺酸与葡萄糖代谢之间存在一致的关联。没有观察到其他 PFAS 和葡萄糖代谢的一致关联。

讨论：

青少年接触全氟己烷磺酸与女性葡萄糖代谢失调有关，这可能是由于$\mathrm{\beta }\text{-细胞}$功能。这些关联出现在青春期，并且在青春期后最为明显。https://doi.org/10.1289/EHP9200