Elucidating the role of adipocytokines and insulin-like growth factors in the pathogenesis of metabolic diseases linked to early life environmental pollutant exposures

Principal Investigator: Damaskini Valvi, Assistant Professor, Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai

Developmental exposure to persistent organic pollutants is associated with increased risks for obesity and related metabolic diseases in later life. In vitro and in vivo evidence suggests that these effects may be mediated through hormone alterations, including perturbations in adipocytokine expression and/or in the Growth Hormone/Insulin-like Growth Factor -1 (GH/IGF-1) axis that play a critical role in growth and metabolism since the very first years of life. However, the potential role of these hormones in the pollutant-related pathogenesis of metabolic abnormalities is underexplored in prospective birth cohorts. Therefore, this study examines the associations of prenatal and postnatal exposures to environmental pollutants with repeated measures of serum adipocytokines and GH/IGF-1 axis factors from birth through early puberty in children from a Faroese birth cohort with wide exposure ranges to persistent organic pollutants due to frequent fish consumption.

RELATED PUBLICATION: Life-course Exposure to Perfluoroalkyl Substances in Relation to Markers of Glucose Homeostasis in Early Adulthood*

Project objective: The objective of this research is to examine the potential connections between exposure to perfluoroalkyl substances (PFASs) throughout the life course and glucose regulation in adulthood. The study aims to assess insulin sensitivity and beta-cell function in individuals at the age of 28 and analyze the associations between PFAS exposures at various stages of life (including cord blood and serum samples collected at ages 7, 14, 22, and 28) and measures of glucose homeostasis. The research utilizes statistical models to evaluate the relationships between PFAS exposures and glucose regulation, considering exposures at different ages and integrating a life-course perspective.

Project’s alignment with the Hoffman Program on Chemicals and Health mission:This research provides valuable insights into the potential health effects of PFAS exposure on our body’s ability to regulate glucose levels and highlights the relevant of early life exposures and expression of disease in adulthood for example theimpact of sVOC chemicals on the risk of developing type 2 diabetes.

Some key takeaways:

• Exposure to certain chemicals called perfluoroalkyl substances (PFASs) at different stages of life can affect how our body handles glucose, which is the sugar in our blood. Our study found that one particular PFAS called perfluoro octane sulfonate (PFOS) is linked to reduced insulin sensitivity and increased insulin production in response to a glucose test in young adults. Other PFASs showed similar but weaker associations.
• These findings suggest that exposure to PFASs during both early life and adulthood can affect how our body regulates glucose levels. This is important because changes in glucose regulation can increase the risk of developing type 2 diabetes later in life. Previous studies have also shown that PFAS exposure can lead to diabetes-like effects in laboratory experiments.
• While earlier research focused on the effects of PFAS exposure during pregnancy or childhood, this study highlights the importance of considering exposures throughout our entire lives. It suggests that long-term follow-up studies should look at different exposure periods to fully understand how PFAS exposure over a lifetime may contribute to the risk of developing type 2 diabetes.

The study’s strengths include its well-designed approach, large sample size, detailed assessment of PFAS exposure, and thorough evaluation of glucose regulation using a glucose test. However, there are some limitations, such as not having information on participants’ diet and exercise habits, potential restrictions in sample size, and a lack of data on family history of diabetes.

*Valvi D, Højlund K, Coull BA, Nielsen F, Weihe P, Grandjean P. Life-course Exposure to Perfluoroalkyl Substances in Relation to Markers of Glucose Homeostasis in Early Adulthood. J Clin Endocrinol Metab. 2021 Jul 13;106(8):2495-2504. doi: 10.1210/clinem/dgab267. PMID: 33890111; PMCID: PMC8277200.