Elsevier

Environmental Pollution

Volume 267, December 2020, 115607
Environmental Pollution

Urinary organophosphate esters metabolites, glucose homeostasis and prediabetes in adolescents

https://doi.org/10.1016/j.envpol.2020.115607Get rights and content

Highlights

  • Data from NHANES 2011–2014 were used to investigate the associations of urinary OPEs metabolites with prediabetes and glucose homeostasis in adolescents.

  • The associations of OPEs metabolites with prediabetes and indices of glucose homeostasis varied by sex.

  • BDCIPP was positively associated with prediabetes and 2 h-OGTT in female adolescents.

  • DNBP was consistently inversely associated with prediabetes and multiple indicators of glucose homeostasis in male counterparts.

Abstract

Background

Emerging experimental evidence indicates that organophosphate esters (OPEs) can trigger glucose metabolic disorders. However, human evidence, especially in adolescents, is unavailable.

Objectives

We utilized data from the National Health and Nutrition Examination Survey 2011–2014 to evaluate whether urinary OPEs metabolites were associated with prediabetes and glucose homeostasis.

Methods

A total of 349 adolescents (12-19-year old) who provided at least 8 h fasting blood samples, had urinary OPEs metabolites detected were included. Prediabetes was defined according to the levels of fasting plasma glucose (FPG), 2-h post oral plasma glucose (2 h-OGTT) and glycated hemoglobin A1c (HbA1c). The homeostatic model assessment (HOMA-IR) and the Single Point Insulin Sensitivity Estimator (SPISE) were used to assess insulin resistance and sensitivity, respectively. Multiple binary logistic and linear regressions were used to evaluate the associations with prediabetes and indices of glucose homeostasis. The least absolute shrinkage and selection operator (LASSO) regression was used to assess the associations in a multi-pollutant context.

Results

After adjusting for covariates, certain urinary OPEs metabolites were associated with prediabetes and indices of glucose homeostasis in all adolescents. Stratified analyses by sex revealed that such associations were largely sex-dependent. In females, the multiple pollutant models showed that bis(1,3–32 dichloro-2-propyl) phosphate (BDCIPP) was positively associated with prediabetes [odds ratio (OR) = 2.51, 95%CI:1.29, 4.89, for one scaled unit increase in exposure] and 2 h-OGTT (β = 0.07, 95%CI:0.01,0.12); bis(2-chloroethyl) phosphate (BCEP) was negatively associated with fasting insulin (β = −0.10, 95%CI: 0.19,-0.01) and HOMA-IR (β = −0.10, 95%CI: 0.19,-0.003); and detectable bis(1-choloro-2-propyl) phosphate (BCIPP) (>LOD vs < LOD) was inversely associated with 2 h-OGTT (β = −0.11, 95%CI: 0.21,-0.02). In males, consistent inverse associations were found for detectable di-n-butyl phosphate (DNBP) with prediabetes, FPG, 2 h-OGTT, fasting insulin and HOMA-IR.

Conclusion

Urinary OPEs metabolites were associated with prediabetes and indices of glucose homeostasis in adolescents. But such associations varied by sex. Future studies with multiple measurements of OPEs exposure are needed to confirm our findings.

Introduction

Prediabetes is a high-risk state for the development of diabetes, posing a greater risk to nephron/neuropathies (Tabák et al., 2012). Amid the pandemic of type 2 diabetes worldwide, the rapidly enlarging adolescence population with prediabetic or diabetic traits is alarming (Andes et al., 2019; Newton et al., 2016; Nsiah-Kumi et al., 2013). Recent data from the 2005–2016 National Health and Nutrition Examination Survey (NHANES) suggested that there are nearly 20% of 12–19-year old adolescents have prediabetes in the U.S (Andes et al., 2019). Although traditional factors such as obesity, lack of physical activity, sedentary lifestyle, and overconsumption of calorie and fat were thought to be responsible for the epidemic of prediabetes in adolescents, exposure to environmental chemicals, particularly the endocrine disruptors, may also play an important role (Sargis and Simmons, 2019).

Organophosphate esters (OPEs) are a class of increasingly used substitutes of brominated flame retardants (BFRs) (Blum et al., 2019; Van der Veen and De Boer, 2012). The global annual production of OPEs has been dramatically increased following the phase-out of BFRs. Although known as flame retardants, unlike most of BFRs, OPEs are not tightly bound to the base materials in products, and have been additionally used as plasticizers and gradients in various products, including personal care products (Blum et al., 2019; Van der Veen and De Boer, 2012). In contrast to the persistence of BFRs in human body, OPEs are readily metabolized in the liver and excreted into urine (Van der Veen and De Boer, 2012). The estimated biological half-lives in humans are almost on the orders hours to days (Van den Eede et al., 2016; Wang et al., 2020). Human exposure to OPEs occurs via a variety of routes, such as the inhalation of indoor dusts, diet-related intake, hand-to-mouth and dermal contact with OPEs containing products (e.g., hand wipes and nail polishing materials) (Blum et al., 2019; Doherty et al., 2019; Van der Veen and De Boer, 2012).

The omnipresence of OPEs in the residential environments and consumer products has resulted in the near-ubiquitous exposure in humans. Monitoring data revealed that more than 80% percent of the general U.S. population have detectable levels of several major OPEs metabolites (Ospina et al., 2018), such as bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), dibutyl phosphate (DPHP), and bis(2-chloroethyl) phosphate (BCEP), whose concentrations have been steadily climbing since 2000s (Hoffman et al., 2017). Moreover, children and adolescents are found to be exposed at a higher level of OPEs exposure. For instance, the levels of BDCIPP and DPHP were significantly higher than those in adults (Doherty et al., 2019; Van den Eede et al., 2015), suggesting that children and adolescents may be at a greater risk.

Evidence from experimental studies indicated that OPEs may be a class of endocrine disrupting chemicals (EDCs) as they are able to disrupt the carbohydrate metabolism (Du et al., 2016; Wang et al., 2018) and glucose homeostasis (Wade et al., 2019), induce insulin resistance (Green et al., 2017; Wang et al., 2019), and promote adipogenesis (Wang et al., 2019). Increasing evidence also shows that OPEs exposure was associated with multiple adverse effects such as thyroid dysfunction (Kim et al., 2015; Liu et al., 2019; Preston et al., 2017) and altered production or action of sex hormones (Liu et al., 2012, 2013; Luo et al., 2020a). Such metabolic disruptions were chiefly mediated by altered activities of multiple nuclear receptors [e.g., peroxisome proliferator activated receptors (PPARs) (Fang et al., 2015; Pillai et al., 2014), thyroid receptors (Liu et al., 2019; Wang et al., 2013), estrogen receptors (ERs), androgen receptors (ARs) (Krumm et al., 2018), and mineralocorticoid and glucocorticoid receptors (Zhang et al., 2017)], genes expressions in arcuate nucleus (ARC) region (the key regulator of energy homeostasis) (Krumm et al., 2018), and mitochondrial dysfunction (Li et al., 2017).

However, whether the exposure to OPEs was associated with metabolic dysfunction, especially prediabetes, and alterations of glucose metabolism in adolescents is largely unknown. Thus, we utilized the data from NHANES, a publicly accessible data platform that provides unique and detailed information on OPEs exposure and cardiometabolic profiles in the U.S. general population, to investigate the associations of urinary OPEs metabolites with prediabetes and glucose homeostasis in adolescents. The findings may provide valuable hints on the contribution of increasing used environmental stressors, like OPEs, to the epidemic of prediabetes in adolescents.

Section snippets

Data source and population

NAHENS is an ongoing national survey with a multi-stage complex sampling design conducted by the Center of Disease Control and Prevention (Johnson et al., 2014). The survey aims to investigate the health and nutritional status of noninstitutionalized adults and children in the U.S. Participants in NHANES all completed a set of comprehensive questionnaires, and received physical examinations in a mobile examination center where blood and urine samples were collected. All procedures and contents

Descriptive statistics

Fig. 1 presents the participants selection process. Overall, 349 nondiabetic and non-pregnant adolescents who had indices of prediabetes and glucose homeostasis measured in at least 8 h fasting blood samples and provided complete data on urinary OPEs metabolites were initially selected. Of these, 49 adolescents with missing values on at least one of the demographic characteristics were further excluded, resulting in a total of 300 adolescents available for a complete case analysis for

Discussion

Our study provides the first epidemiological evidence on the associations of urinary OPEs metabolites with prediabetes and indices of glucose homeostasis in adolescents. The associations varied by OPEs metabolites and sex. Specifically, elevated odds of being prediabetes and increased 2 h-OGTT level were associated with BDCIPP in female adolescents, while DNBP presented consistent inverse associations with prediabetes and indices of glucose homeostasis in males. Meanwhile, an inverse

CRediT authorship contribution statement

Kai Luo: Conceptualization, Methodology, Writing - original draft. Ruxianguli Aimuzi: Software, Validation, Data curation. Yuqing Wang: Resources, Investigation, Visualization. Min Nian: Resources, Investigation. Jun Zhang: Conceptualization, Methodology, Supervision, Writing - review & editing.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgement

This study was partly funded by the National Natural Science Foundation of China (41991314 and 81530086) and Shanghai Municipal Health and Family Planning Commission (2020CXJQ01). The authors greatly appreciate all the participants in NHANES for making the current study possible.

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