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Review
. 2021 May 22;20(1):63.
doi: 10.1186/s12940-021-00740-z.

A pathway level analysis of PFAS exposure and risk of gestational diabetes mellitus

Rahel L Birru  1 , Hai-Wei Liang  1 , Fouzia Farooq  1 , Megha Bedi  2 , Maisa Feghali  3 , Catherine L Haggerty  1 , Dara D Mendez  1 , Janet M Catov  1   3 , Carla A Ng  2   4 , Jennifer J Adibi  5   6
Affiliations
Review

A pathway level analysis of PFAS exposure and risk of gestational diabetes mellitus

Rahel L Birru et al. Environ Health. .

Abstract

Per- and polyfluoroalkyl substances (PFAS) have been found to be associated with gestational diabetes mellitus (GDM) development, a maternal health disorder in pregnancy with negative effects that can extend beyond pregnancy. Studies that report on this association are difficult to summarize due to weak associations and wide confidence intervals. One way to advance this field is to sharpen the biologic theory on a causal pathway behind this association, and to measure it directly by way of molecular biomarkers. The aim of this review is to summarize the literature that supports a novel pathway between PFAS exposure and GDM development. Epidemiological studies demonstrate a clear association of biomarkers of thyroid hormones and glucose metabolism with GDM development. We report biologic plausibility and epidemiologic evidence that PFAS dysregulation of maternal thyroid hormones and thyrotropin (TSH) may disrupt glucose homeostasis, increasing the risk of GDM. Overall, epidemiological studies demonstrate that PFAS were positively associated with TSH and negatively with triiodothyronine (T3) and thyroxine (T4). PFAS were generally positively associated with glucose and insulin levels in pregnancy. We propose dysregulation of thyroid function and glucose metabolism may be a critical and missing component in the accurate estimation of PFAS on the risk of GDM.

Keywords: Gestational diabetes mellitus; Glucose metabolism; PFAS; Thyroid hormones.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Novel biomarkers in the pathway between PFAS exposure and gestational diabetes mellitus (GDM) development. PFAS targets the hypothalamic–pituitary–thyroid axis, disrupting thyroid hormone homeostasis, which may contribute to GDM development. While the thyroid may be the main target for hormone disruption, PFAS can also exert toxicity to other tissues involved in this regulatory pathway. Abbreviations: FT3, free triiodothyronine; FT4, free thyroxine; hCG, human chorionic gonadotropin; HOMA-%β, homeostatic model assessments of β-cell function; HOMA-IR, homeostatic model of assessment of insulin resistance; T3, triiodothyronine; T4, thyroxine; TRH, thyrotropin-releasing hormone; TSH, thyrotropin
Fig. 2
Fig. 2
Summary statistics of selected PFAS on gestational diabetes mellitus (GDM) development in the epidemiologic literature. Abbreviations: HR, hazard ratio; OR, odds ratio; PFOA, perfluorooctanoic acid; PFOS, perfluorooctane sulfonate; PFHxS, perfluorohexane sulfonic acid; RR, risk ratio
Fig. 3
Fig. 3
Summary statistics of selected PFAS on thyrotropin (TSH) in the epidemiologic literature. Displayed is a representative forest plot of the PFAS and TSH relationship for selected PFAS where not all units are the same across all studies. The aim is to assess the overall direction and strength of association. Abbreviations: PFOA, perfluorooctanoic acid; PFOS, perfluorooctane sulfonate; PFHxS, perfluorohexane sulfonic acid; PFNA, perfluorononanoic acid; PFUnDA, perfluoroundecanoate; PFDoDA, perfluorododecanoate; TSH, thyrotropin
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