Mediation analysis for the relationship between urinary phthalate metabolites and type 2 diabetes via oxidative stress in a population in Jeddah, Saudi Arabia

Li, Adela Jing; Martinez-Moral, Maria-Pilar; Al-Malki, Abdulrahman L.; Al-Ghamdi, Maryam A.; Al-Bazi, Maha M.; Kumosani, Taha A.

doi:10.1016/j.envint.2019.01.082

Cited by 57 publications

(37 citation statements)

References 43 publications

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“…Previously, BPA and phthalates have been linked to both impaired glucose metabolism 6,11,37,72,73 , as well as T2D 26,47,[73][74][75] . In this study, we did not find any significant associations between EDCs and glycaemic traits.…”

Section: Discussionmentioning

confidence: 99%

Exposure to Endocrine Disrupting Chemicals in the Dutch general population is associated with adiposity-related traits

Meer

Faassen

Beek

et al. 2020

Sci Rep

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endocrine Disrupting chemicals (eDcs) have been linked to a variety of cardiometabolic diseases. Yet, few studies have investigated the exposure to eDcs and cardiometabolic health taking lifestyle into account. We aimed to assess exposure to five parabens, three bisphenols and thirteen metabolites of in total eight phthalates in a general Dutch population and to investigate their association with cardiometabolic traits. In 662 adult subjects from the population-based Lifelines cohort, 21 EDC analytes were measured in 24-hour urine collected in 2012, using LC-MS/MS. Association analyses between cardiometabolic traits and eDc concentrations were performed using multivariate linear models adjusting for age, sex, education, smoking, diabetes, physical activity and caloric intake. Quartile analyses were performed to assess linearity. Bisphenol A, four parabens and eight phthalate metabolites were detected in 84-100% of the samples. Adjusted associations for MiBP and MBzP and adiposity-related traits were robust for multiple testing (Beta's, BMI: 1.12, 2.52; waist circumference: 0.64, 1.56, respectively; FDR < 0.009). Associations for triglyceride, HDL-cholesterol, glucose and blood pressure were not. Linearity was confirmed for significant associations. Exposure to EDCs in the Dutch population is ubiquitous. We found direct associations between phthalates and adiposity-related traits. Prospective studies are needed to confirm these findings. During the past decades, cardiovascular diseases (CVD) and type 2 diabetes (T2D) have risen to epidemic proportions 1,2. These diseases are responsible for severe complications including myocardial infarction, stroke, blindness, lower limb amputation and renal failure, and are strongly correlated with a collection of asymptomatic cardiometabolic abnormalities such as (central) obesity, impaired glucose tolerance, elevated triglycerides, a low HDL-cholesterol, and hypertension 3,4. A combination of at least three of the above stated cardiovascular abnormalities defines the metabolic syndrome (MetS) 1. Risk factors include a combination of genetic predisposition and lifestyle (e.g. lack of physical activity, imbalanced diet). Meanwhile, a wide variety of synthetic chemicals have been introduced in our environment, some of which have been shown to cause metabolic disruptions in animal and human studies 5. Endocrine Disrupting Chemicals (EDCs) such as parabens, phenols and phthalates have been shown to be associated with the MetS 6,7 , obesity 8,9 and T2D 10,11. These EDCs have in common that they are widely used as preservatives and plasticizers and can therefore be found in a wide variety of consumer products. Exposure occurs through ingestion, inhalation, and dermal contact 12,13. Although parabens, phenols and phthalates have in common that they are metabolized and excreted fairly quickly (i.e. half-lives <24 h) and therefore are considered non-persistent 14-16 , exposure is ubiquitous throughout life and reported to be global 17-20. However, to date little is known about exposure...

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Section: Discussionmentioning

confidence: 99%

Exposure to Endocrine Disrupting Chemicals in the Dutch general population is associated with adiposity-related traits

Meer

Faassen

Beek

et al. 2020

Sci Rep

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“…In the 2001–2008 study of diabetes prevalence in women in the U.S. National Health and Nutrition Survey, MBzP (3rd and 4th quartiles) had significantly higher diabetes people than those of 1st quartile [ 12 ]. In a 2019 study that analyzed the urinary phthalate metabolite concentrations of 101 type 2 diabetes mellitus individuals who are residing in Jeddah, Saudi Arabia, and the Middle East, DEHP (3rd quartile), MEHHP (2nd, 3rd, and 4th quartiles), MEOHP (3rd quartile), and MECPP (3rd quartile) had significantly higher diabetes people than those of 1st quartile [ 13 ]. The results of this study were consistent with those of existing studies.…”

Section: Discussionmentioning

confidence: 99%

“…In studies conducted in countries such as China, the United States and the Middle East, the higher urinary phthalate metabolites, the higher the prevalence of diabetes. [ 11 12 13 ]…”

Section: Introductionmentioning

confidence: 99%

Relationship between urinary phthalate metabolites and diabetes: Korean National Environmental Health Survey (KoNEHS) cycle 3 (2015–2017)

Nam

Kim

Yang

et al. 2020

Ann Occup Environ Med

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Background We aimed to determine relationship diabetes according to urinary phthalate metabolites using adult data from Korean National Environmental Health Survey cycle 3 (2015–2017). Method This study was conducted on 3,781 adults aged 19 years and older (1,648 men and 2,133 women) based on KoNEHS cycle 3. Participants' data were analyzed by gender; Relationship between phthalate metabolites in the urine and diabetes was analyzed by dividing the sociodemographic variables, health behavior-related variables, and urinary phthalate metabolite concentrations into quartiles. To determine the relationship between urinary phthalate metabolites and the prevalence of diabetes, the odds ratio (OR) was calculated using logistic regression analysis. Results Based on the 1st quartile of each metabolite, the ORs for di-2-ethylhexyl phthalate (DEHP) (4th quartile), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) (2nd quartile, 3rd quartile and 4th quartile), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) (4th quartile), mono-(2-ethyl-5-carboxypentyl) phthalate (MECCP) (4th quartile), mono-n-butyl phthalate (MnBP) (3rd quartile and 4th quartile), mono-benzyl phthalate (MBzP) (2nd quartile) and 4th quartile), and mono (3-carboxypropyl) phthalate (MCPP) (3rd quartile and 4th quartile) were significantly higher after the adjustment in men. The ORs for DEHP (2nd quartile, 3rd quartile and 4th quartile), MEHHP (2nd quartile, 3rd quartile and 4th quartile), MEOHP (4th quartile), MECCP (4th quartile), MBzP (4th quartile), and MCPP (4th quartile) were significantly higher after the adjustment in women. Conclusion This study investigated relationship between urinary phthalate metabolites and diabetes. The higher urinary phthalate metabolites, the higher the prevalence of diabetes. Further regulation of phthalate may be needed, and further studies are warranted to confirm the association between phthalate concentration and other chronic diseases (such as hypertension, hyperlipidemia, and cardiovascular disease).

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“…Furthermore, several recent studies have documented associations between other more common and low-level synthetic chemical exposures, such as bisphenol A (BPA) and phthalates, and kidney function [15][16][17]. These exposures have been hypothesized to affect kidney function through promotion of oxidative stress [18][19][20][21][22][23][24]. Because it has been shown that the kidney is vulnerable to environmental toxicants, especially prenatally and in early life [14,25], these exposures may be particularly relevant to pediatric CKD.…”

Section: Introductionmentioning

confidence: 99%

Serially assessed bisphenol A and phthalate exposure and association with kidney function in children with chronic kidney disease in the US and Canada: A longitudinal cohort study

Jacobson

Liu

et al. 2020

PLoS Med

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Background Exposure to environmental chemicals may be a modifiable risk factor for progression of chronic kidney disease (CKD). The purpose of this study was to examine the impact of serially assessed exposure to bisphenol A (BPA) and phthalates on measures of kidney function, tubular injury, and oxidative stress over time in a cohort of children with CKD. Methods and findings Samples were collected between 2005 and 2015 from 618 children and adolescents enrolled in the Chronic Kidney Disease in Children study, an observational cohort study of pediatric CKD patients from the US and Canada. Most study participants were male (63.8%) and white (58.3%), and participants had a median age of 11.0 years (interquartile range 7.6 to 14.6) at the baseline visit. In urine samples collected serially over an average of 3.0 years (standard deviation [SD] 1.6), concentrations of BPA, phthalic acid (PA), and phthalate metabolites were measured as well as biomarkers of tubular injury (kidney injury molecule-1 [KIM-1] and neutrophil gelatinase-associated lipocalin [NGAL]) and oxidative stress (8-hydroxy-2′-deoxyguanosine [8-OHdG] and F 2 -isoprostane). Clinical renal function measures included estimated glomerular filtration rate (eGFR), proteinuria, and blood pressure. Linear mixed models were fit to estimate the associations between urinary concentrations of 6 chemical exposure measures (i.e., BPA, PA, and 4 phthalate metabolite groups) and clinical renal outcomes and urinary concentrations of KIM-1, NGAL, 8-OHdG, and F 2 -isoprostane controlling for sex, age, race/ethnicity, glomerular status, birth weight, premature birth, angiotensin-converting enzyme inhibitor use, angiotensin receptor blocker use, BMI z- score for age and sex, and urinary creatinine. Urinary concentrations of BPA, PA, and phthalate metabolites were positively associated with urinary KIM-1, NGAL, 8-OHdG, and F 2 -isoprostane levels over time. For example, a 1-SD increase in ∑di-n-octyl phthalate metabolites was associated with increases in NGAL (β = 0.13 [95% CI: 0.05, 0.21], p = 0.001), KIM-1 (β = 0.30 [95% CI: 0.21, 0.40], p < 0.001), 8-OHdG (β = 0.10 [95% CI: 0.06, 0.13], p < 0.001), and F 2 -isoprostane (β = 0.13 [95% CI: 0.01, 0.25], p = 0.04) over time. BPA and phthalate metabolites were not associated with eGFR, proteinuria, or blood pressure, but PA was associated with lower eGFR over time. For a 1-SD increase in ln-transformed PA, there was an average decrease in eGFR of 0.38 ml/min/1.73 m 2 (95% CI: −0.75, −0.01; p = 0.04). Limitations of this study included utilization of spot urine samples for exposure assessment of non-persistent compounds and lack of specific information on potential sources of exposure. ...

show abstract

Mediation analysis for the relationship between urinary phthalate metabolites and type 2 diabetes via oxidative stress in a population in Jeddah, Saudi Arabia

Cited by 57 publications

References 43 publications

Exposure to Endocrine Disrupting Chemicals in the Dutch general population is associated with adiposity-related traits

Exposure to Endocrine Disrupting Chemicals in the Dutch general population is associated with adiposity-related traits

Relationship between urinary phthalate metabolites and diabetes: Korean National Environmental Health Survey (KoNEHS) cycle 3 (2015–2017)

Serially assessed bisphenol A and phthalate exposure and association with kidney function in children with chronic kidney disease in the US and Canada: A longitudinal cohort study

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