Serum perfluorinated chemicals, glucose homeostasis and the risk of diabetes in working-aged Taiwanese adults☆
Introduction
Extensive industrial and commercial applications of perfluoroalkyl and polyfluoroalkyl substances (PFASs) as surfactants, emulsifiers, repellents, paper and textile coatings, non-stick frypan coatings, and food packaging and their persistence in the environment has led to a global PFC exposure (Begley et al., 2005, Buck et al., 2011, Calafat et al., 2007, Lau et al., 2007). The human exposure of PFASs in both occupational and general populations has been recognized (Calafat et al., 2007, Costa et al., 2009, Fei et al., 2007). Although the routes of human exposure remain unclear, potential sources include food (e.g., contaminated marine products and food packaging contamination), drinking polluted water, and indoor dust (Lau et al., 2007).
PFASs are a generic term for a family of perfluoroalkyl and polyfluoroalkyl acids (PFAAs) that are composed of a fluorinated carbon backbone with varying length and a charged carboxylate or sulfonate functional group (Buck et al., 2011, Furl et al., 2010). This structure makes them resistant to biodegradation and dramatically lower surface tension (Conder et al., 2008). The most widely known perfluorinated carboxylates are perfluorooctanoic acid (PFOA) and perfluorononanoic acid (PFNA) and for perfluorinated sulfonates, they are perfluorooctyl sulfonic acid (PFOS) and perfluorohexane sulfonic acid (PFHxS) (Lau et al., 2007). PFASs are well absorbed orally and are slowly eliminated in human body without further biotransformation (Lau et al., 2007). The estimated mean serum half-lives are about 5.4 and 3.8 years for PFOS and PFOA, respectively (Olsen et al., 2007).
Increasing evidence has linked PFASs to diverse health effects including carcinogenesis (EPA, 2014), atherosclerosis (Lin et al., 2013), lipid metabolism (Fletcher et al., 2013), glucose homeostasis (Lin et al., 2009), and developmental toxicity (Lau et al., 2007, White et al., 2007). However, the potential mechanisms underlying glucose metabolism disturbance by PFASs remains controversial. Experimental studies has shown the obesity-related metabolic effects of PFASs including endocrine disrupting capacity and differential activation of nuclear receptors especially peroxisome proliferator-activated receptors (PPARs) (White et al., 2011). Recent animal studies also support the potential diabetogenic effect of PFASs (Lv et al., 2013, Wan et al., 2014, Wang et al., 2014). Epidemiologic studies investigating the association between PFASs and diabetes are scarce and the results are not consistent. In a retrospective occupational cohort study, PFOA was associated with a statistically significant increase in diabetes mortality (DuPont, 2006). A Swedish cross-sectional study of the elderly found a significant association between PFASs and diabetes prevalence (Lind et al., 2014). However, this finding was not supported by a community-based case–control study in the C8 Health Project (MacNeil et al., 2009). Among studies using insulin resistance as the endpoint, findings were also inconsistent. In NHANES 1999–2000 and 2002–2003 (Lin et al., 2009) and Danish overweight children (Timmermann et al., 2014), PFASs were associated with higher insulin resistance. However, in NAHNES 2002–2003 and cycle 1 of the Canadian Health Measure Survey (2007–2009), the association between PFASs and insulin resistance was not found (Fisher et al., 2013, Nelson et al., 2010).
The oral glucose tolerance test (OGTT), although costly and cumbersome, is currently the gold standard epidemiological and clinical diagnostic test for diabetes (WHO, 1980). The 2-h post challenge glucose level is also a better predictor of coronary heart disease and cardiovascular mortality than fasting glucose (Qiao et al., 2002). To further clarify the relationship between PFASs and glucose homeostasis, we conducted a cross-sectional study in a community-based sample of adults in Taiwan using OGTT to verify diabetes status and using area under the curve (AUC) to summarize the glucose tolerance curve.
Section snippets
Study population
Volunteers aged 20–60 years old were recruited from our previous case–control study conducted at outpatient cardiology clinics in the National Taiwan University Hospital, Taipei, Taiwan from 2009 to 2011 (Cheng et al., 2014, Ding et al., 2014). Consecutive patients were invited to participate as the control group investigating work-related factors and cardiovascular disease (Cheng et al., 2014, Ding et al., 2014). A total of 592 participants who consented to the questionnaire, interview, and
Results
Sociodemographic characteristics of the study participants are described in Table 1. The prevalence of diabetes in this population was 6.8%, which was comparable with the prevalence of diabetes in two previous Taiwan studies, ranging from 7.8 to 9.1% (Chang et al., 2010, Wang et al., 2012). Median PFOA, PFOS, PFNA, PFUA was 8.0, 3.2, 3.8 and 6.4 ng/ml, respectively (Table 1). The Pearson correlation matrix among the analyzed PFASs was provided in Supplementary Fig. 1(both Pearson and Spearman
Discussion
In this working-age population free of overt cardiovascular disease and clinical diabetes, the highest quartile of serum PFOS was associated with a higher and steeper post load glucose trajectory, a greater tendency toward glucose intolerance, and a 3.4 times greater prevalence of diabetes compared with the lowest quartile. In contrast, an opposite relationship was found between the study outcomes including markers of glucose homeostasis and diabetes prevalence and the other PFASs, including
Conclusion
Our findings support that PFOS may play an important role in glucose homeostasis by exhibiting a steeper upward post load glucose trajectory and the higher prevalence of diabetes among a Taiwanese working-age population free of clinical cardiovascular disease. In contrast, PFOA, PFNA, and PFUA showed a potential protective effect against glucose intolerance and the risk of diabetes. Experimental and mechanistic studies at relevant exposure levels and prospective studies in humans are needed to
Author contributions
TCS, CCK, and PCC: Prepared research data, conducted statistical analysis, and manuscript writing.
JJH, MFC, and GWL: Biochemical and physiology counseling and manuscript revision and editing.
Acknowledgments
This study was supported by grants from National Health Research Institute of Taiwan (EX97-9721PC, EX97-9821PC, EX97-9921PC, EX97-10021PC), and from Ministry of Science and Technology (101–2314-B-002-184-MY3), and from Taiwan and the Environmental Medicine Collaboration Center (NTUH 103 A123 and 104 A123). This work was supported in part by the 3rd core facility at National Taiwan University Hospital.
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