Diabetes Care. 2016 Oct;39(10):1745-51. doi: 10.2337/dc16-0269.

Longitudinal Associations of Exposure to Perfluoroalkylated Substances in Childhood and Adolescence and Indicators of Adiposity and Glucose Metabolism 6 and 12 Years Later: The European Youth Heart Study.

PubMed link

 

Supplement:

The global epidemic of obesity and hence also diabetes have been sought to be explained by high energy consumption in interaction with low energy expenditure. Scientists though sow doubt about this explanation alone because the obesity epidemic occurred relatively rapidly to change the genetic predisposition underlying the body’s weight-control mechanisms. Also the approach is rather behavioristic to claim that overeating and inactivity at individual level have caused the epidemic alone. Thus Baillie-Hamilton constructed a hypothesis to compare the production of synthetic organic chemicals and the percentage of overweight adults in the US during the twentieth century [1]. Especially from the 1980’s the two timelines have coincided. We have built upon the existing hypothesis and literature pointing towards persistent organic pollutants such as perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) working as antagonists for peroxisome proliferator-activated receptors (PPARs) leading to disturbance in lipid and steroid metabolism [2] and hence overweight and impaired glycemic control [3, 4].

 

 

Figure 1. Perfluoroalkylated substances including PFOS and PFOA are man-made chemicals used as surfactants in a wide range of consumer products due to their water- and soil-repellent properties. They function as impregnation in outdoor clothing and furnishings, as coating in cookware and foodstuff packaging, and as surfactant in paint, wax and polish.

 

Our recent study published in Diabetes Care investigated how exposure to PFOS and PFOA in childhood may affect markers of adiposity and glucose metabolism in adolescence and young adulthood. We hypothesized that early exposure during growth and development has a potential to impair weight-control mechanisms and glucose homeostasis later in life. What we found was a positive association between childhood exposure to PFOS and indicators of overweight in adolescence and young adulthood. In relation to markers of glucose metabolism we found a negative association between childhood exposure to PFOA and beta-cell function but only in adolescence, indicating an impaired pancreatic beta-cell function. We did not find evidence for a relationship between exposure levels in adolescence and outcomes in adulthood.

 

This study suggests that childhood marks a susceptible period for toxicity to the endocrine system through disruption of hormones responsible for the metabolism of fat and glucose. Our results also indicate that PFOS and PFOA may work through different pathways and target different steps in the metabolism.

 

 

Figure 2. The European Youth Heart Study is an ongoing cohort study initiated in 1997. Participants have been followed from age 9 to age 15 and age 21 with physical examinations related to cardiometabolic health. As a sub-project blood samples have been analyzed for persistent organic pollutants including PFOS and PFOA.

 

Our longitudinal study design enables us to draw some causal inference due to the time between the measuring points, providing time for markers of overweight and diabetes to develop. Our setup does not allow us to predict overweight or prediabetes caused by earlier exposure (e.g. prenatal exposure), though. As we account for baseline overweight and prediabetes we fail to include participants who were already overweight or pre-diabetic in childhood. However, if we had decided not to account for baseline values, our causal interpretation of the results would diminish as we would no longer be able to distinguish between overweight and prediabetes caused by endocrine disrupting chemicals or other factors including health behavior and genetic predisposition. Having said that, it is most likely an interaction between all three that causes overweight and diabetes to develop.

 

References:

[1] Baillie-Hamilton PF. Chemical toxins: a hypothesis to explain the global obesity epidemic. J Altern Complement Med 2002; 8(2):185.192

[2] Kelishadi R, Poursafa P, Jamshidi F. Role of environmental chemicals in obesity: a systematic review on the current evidence. J Environ Public Health 2013; 2013:896789

[3] Halldorsson TI, Rytter D, Haug LS, et al. Prenatal exposure to perfluorooctanoate and risk of overweight at 20 years of age: a prospective cohort study. Environ Health Perspect 2012; 120:668-673

[4] Lin CY, Chen PC, Lin YC, Lin LY. Association among serum Perfluoroalkyl chemicals, glucose homeostasis, and metabolic syndrome in adolescents and adults. Diabetes Care 2009; 32:702-707