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September 22, 2021
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Girls exposed to endocrine-disrupting chemical have higher glucose level as adults

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Girls exposed to high levels of perfluorohexane sulfonate have a higher risk for dysregulated glucose metabolism during and after puberty, according to findings published in Environmental Health Perspectives.

Jesse Goodrich

“Previous research has shown that perfluoroalkyl and polyfluoroalkyl substances (PFAS) have endocrine- and metabolism-disrupting properties, both in animals and in humans,” Jesse Goodrich, PhD, a postdoctoral scholar in the department of population and public health sciences at the University of Southern California Keck School of Medicine, told Healio. “Previous research has also shown that children may be more susceptible to the negative health effects of endocrine-disrupting chemicals compared to adults. However, very few studies have examined how PFAS impact the metabolic health of children.”

Endocrine Disruptors 2019
Source: Adobe Stock

Goodrich and colleagues analyzed data from 310 participants in the Study of Latino Adolescents at Risk of Type 2 Diabetes (SOLAR), in which Hispanic or Latino children aged 8 to 13 years with a BMI in the 85th percentile or higher, a family history of type 2 diabetes and free of diabetes underwent annual clinical visits for a median of 2.2 years. To test the generalizability of associations between PFAS exposure and glucose homeostasis in SOLAR, blood samples were analyzed in a subset of 137 young adults participating in the Southern California Children’s Health Study (CHS). Participants in CHS were aged 18 to 23 years, were free of diabetes and underwent a single clinical visit between 2014 and 2018. Participants were selected based on having a BMI in the 85th percentile or higher in the ninth or 10th grade. All participants in the analysis underwent a 2-hour oral glucose tolerance test at each clinical visit. Blood samples were collected at 15, 30, 45, 60 and 120 minutes in SOLAR and at 30, 60, 90 and 120 minutes in CHS. Raw liquid chromatography high-resolution mass spectrometry was used to measure PFAS levels.

Participants with a PFAS level in the top one-third tertile for their cohort were defined as having high exposure, with cutoffs of 20.8 ng/dL for perfluorooctane sulfonate (PFOS), 2 ng/dL for perfluorohexane sulfonate (PFHxS) and 0.7 ng/dL for perfluorononanoic acid (PFNA).

Associations between PFHxS exposure and altered glucose concentration were found in girls participating in SOLAR, with the associations becoming more pronounced later in puberty. During late puberty, high PFHxS exposure was associated with a 21 mg/dL higher glucose concentration at 60 minutes of OGTT compared with lower exposure (95% CI, 10-31; P = .0001), and a 12 mg/dL higher OGTT overall (95% CI, 1-22; P = .03). After puberty, girls with a high PFHxS level had a 25 mg/dL higher glucose at 60 minutes of the OGTT compared with those with low levels (95% CI, 12-39; P < .0001) and a 15 mg/dL higher glucose concentration overall (95% CI, 1-28; P = .04). Young adult women participating in CHS had a 26 mg/dL higher glucose at 60 minutes of OGTT with a high PFHxS level compared with those with low exposure (95% CI, 6-46; P = .02). No associations were observed for men.

“We were surprised by how consistent our findings were between the two groups included in this study,” Goodrich said. “In both groups, we found almost identical relationships between PFAS and blood sugar regulation in women. The consistency between groups makes it unlikely that our findings were just by chance.”

For girls participating in SOLAR, increased PFHxS exposure was associated with increases in glucose area under the curve and HbA1c and decreases in beta-cell functioning. Associations were dependent on pubertal status, with elevated PFHxS levels associated with an 8.9% higher glucose AUC in late puberty (P = .003) and 10.6% higher glucose AUC after puberty (P = .0004). No associations were observed between PFHxS levels and glucose homeostasis markers for adult women or boys and men. In both cohorts, no associations were observed for PFOS, PFNA and perfluorodecanoic acid (PFDA).

Goodrich said researchers are preparing a new study to examine how PFAS works at a cellular level to cause dysregulated glucose metabolism.

“In collaboration with researchers at Yale University, we are starting a new study to examine how PFAS directly impact pancreatic beta cells,” Goodrich said. “Pancreatic beta cells are responsible for releasing insulin and are the primary cells implicated in the pathogenesis of diabetes, and the findings of our study will help to predict how new and emerging PFAS contaminates will impact the risk of diabetes in children.”

For more information:

Jesse Goodrich, PhD, can be reached at jagoodri@usc.edu.