Skip to main content
SpringerLink
Log in

Systematic review and meta-analysis on the association between phthalates exposure and insulin resistance

  • Review Article
  • Published:
Environmental Science and Pollution Research Aims and scope Submit manuscript

Abstract

This study aims to provide an overview of human studies on the association of exposure to phthalates and insulin resistance. We systematically searched human studies available until 15 January 2018.We conducted a literature search in Scopus, ISI Web of Science, PubMed, Google Scholar, and Cochrane Collaboration. We used the following keywords to identify relevant articles: “phthalate”, “phthalate ester”, “metabolic syndrome”, “insulin resistance”, “glucose intolerance”, and “diabetes”. For analyzing data, we conducted meta-analysis using the Stata software. We appraised each study to examine the sources of heterogeneity, including difference in clinical outcomes and exposure measurements. To determine the robustness and whether some of the factors have the highest impact on the results of the present meta-analysis, several sensitivity analyses were conducted. Sensitivity analysis showed that by removing studies with the highest weight and age groups, no change was observed in heterogeneity. Moreover, with excluding the study conducted in Europe, the results remained unchanged and constant. In addition, the funnel plot and Egger’s tests were executed to access publication bias. Both the funnel plots and Egger’s test did not show any evidence of publication bias (P = 0.31). In the random effects meta-analysis of all studies (n = 8), the pooled correlation coefficient between phthalate exposure and HOMA-IR was 0.10 (95% CI; 0.07–0.12, P < 0.001), with significant heterogeneity (P < 0.001, I2 = 85.5%). Our findings revealed positive association between exposure to phthalate metabolites and increased HOMA-IR; this association remained significant even after adjusting the analysis for multiple confounding variables.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Amin MM, Rafiei N, Poursafa P, Ebrahimpour K, Mozafarian N, Shoshtari-Yeganeh B, Hashemi M, Kelishadi R (2018) Association of benzene exposure with insulin resistance, SOD, and MDA as markers of oxidative stress in children and adolescents. Environ Sci Pollut Res 25:34046–34052

    Article  CAS  Google Scholar 

  • Attina TM, Trasande L (2015) Association of exposure to di-2-ethylhexylphthalate replacements with increased insulin resistance in adolescents from NHANES 2009–2012. J Clin Endocrinol Metab 100:2640–2650

    Article  CAS  Google Scholar 

  • Chen S-Y, Hwang J-S, Sung F-C, Lin C-Y, Hsieh C-J, Chen P-C, Su T-C (2017) Mono-2-ethylhexyl phthalate associated with insulin resistance and lower testosterone levels in a young population. Environ Pollut 225:112–117

    Article  CAS  Google Scholar 

  • Dales RE, Kauri LM, Cakmak S (2018) The associations between phthalate exposure and insulin resistance, β-cell function and blood glucose control in a population-based sample. Sci Total Environ 612:1287–1292

    Article  CAS  Google Scholar 

  • Dalsenter P, Santana G, Grande S, Andrade AJ, Araujo S (2006) Phthalate affect the reproductive function and sexual behavior of male Wistar rats. Hum Exp Toxicol 25:297–303

    Article  CAS  Google Scholar 

  • Dirinck E, Dirtu AC, Geens T, Covaci A, Van Gaal L, Jorens PG (2015) Urinary phthalate metabolites are associated with insulin resistance in obese subjects. Environ Res 137:419–423

    Article  CAS  Google Scholar 

  • Goodman M, LaKind JS, Mattison DR (2014) Do phthalates act as obesogens in humans? A systematic review of the epidemiological literature. Crit Rev Toxicol 44:151–175

    Article  CAS  Google Scholar 

  • Hectors TL, Vanparys C, Van Gaal LF, Jorens PG, Covaci A, Blust R (2013) Insulin resistance and environmental pollutants: experimental evidence and future perspectives. Environ Health Perspect 121:1273–1281

    Article  CAS  Google Scholar 

  • Higgins J (2011) Green S. Cochrane handbook for systematic reviews of interventions Version 5.1. 0. The Cochrane Collaboration. Confidence intervals

  • Huang T, Saxena AR, Isganaitis E, James-Todd T (2014) Gender and racial/ethnic differences in the associations of urinary phthalate metabolites with markers of diabetes risk: National Health and Nutrition Examination Survey 2001–2008. Environ Health 13:6

    Article  CAS  Google Scholar 

  • James-Todd T, Stahlhut R, Meeker JD, Powell S-G, Hauser R, Huang T, Rich-Edwards J (2012) Urinary phthalate metabolite concentrations and diabetes among women in the National Health and Nutrition Examination Survey (NHANES) 2001–2008. Environ Health Perspect 120:1307–1313

    Article  Google Scholar 

  • Kang ES, Yun YS, Park SW, Kim HJ, Ahn CW, Song YD, Cha BS, Lim SK, Kim KR, Lee HC (2005) Limitation of the validity of the homeostasis model assessment as an index of insulin resistance in Korea. Metabolism 54:206–211

    Article  CAS  Google Scholar 

  • Kim JH, Park HY, Bae S, Lim Y-H, Hong Y-C (2013) Diethylhexyl phthalates is associated with insulin resistance via oxidative stress in the elderly: a panel study. PLoS One 8:e71392

    Article  Google Scholar 

  • Kimber I, Dearman RJ (2010) An assessment of the ability of phthalates to influence immune and allergic responses. Toxicology 271:73–82

    Article  CAS  Google Scholar 

  • Levy-Marchal C, Arslanian S, Cutfield W, Sinaiko A, Druet C, Marcovecchio ML, Chiarelli F, ESPE-LWPES- ISPAD-APPES-APEG-SLEP-JSPE; Insulin Resistance in Children Consensus Conference Group (2010) Insulin resistance in children: consensus, perspective, and future directions. J Clin Endocrinol Metab 95(12):5189–5198

    Article  CAS  Google Scholar 

  • Lin C-Y, Hsieh C-J, Lo S-C, Chen P-C, Torng P-L, Hu A, Sung F-C, Su T-C (2016) Positive association between concentration of phthalate metabolites in urine and microparticles in adolescents and young adults. Environ Int 92:157–164

    Article  CAS  Google Scholar 

  • Lind PM, Zethelius B, Lind L (2012) Circulating levels of phthalate metabolites are associated with prevalent diabetes in the elderly. Diabetes Care, DC_112396

  • Minatoya M, Araki A, Miyashita C, Sasaki S, Goto Y, Nakajima T, Kishi R (2017) Prenatal di-2-ethylhexyl phthalate exposure and cord blood adipokine levels and birth size: the Hokkaido study on environment and children’s health. Sci Total Environ 579:606–611

    Article  CAS  Google Scholar 

  • Moosazadeh M, Nekoei-moghadam M, Emrani Z, Amiresmaili M (2014) Prevalence of unwanted pregnancy in Iran: a systematic review and meta-analysis. Int J Health Plann Manag 29:e277–e290

    Article  Google Scholar 

  • North ML, Takaro TK, Diamond ML, Ellis AK (2014) Effects of phthalates on the development and expression of allergic disease and asthma. Ann Allergy Asthma Immunol 112:496–502

    Article  CAS  Google Scholar 

  • Reeves KW, Santana MD, Manson JE, Hankinson SE, Zoeller RT, Bigelow C, Hou L, Wactawaski-Wende J, Liu S, Tinker L (2019) Predictors of urinary phthalate biomarker concentrations in postmenopausal women. Environ Res 169:122–130

    Article  CAS  Google Scholar 

  • Smerieri A, Testa C, Lazzeroni P, Nuti F, Grossi E, Cesari S, Montanini L, Latini G, Bernasconi S, Papini AM, Street ME (2015) Di-(2-ethylhexyl) phthalate metabolites in urine show age-related changes and associations with adiposity and parameters of insulin sensitivity in childhood. PLoS One 10:e0117831

    Article  CAS  Google Scholar 

  • Stahlhut RW, van Wijngaarden E, Dye TD, Cook S, Swan SH (2007) Concentrations of urinary phthalate metabolites are associated with increased waist circumference and insulin resistance in adult US males. Environ Health Perspect 115:876–882

    Article  CAS  Google Scholar 

  • Stojanoska MM, Milosevic N, Milic N, Abenavoli L (2017) The influence of phthalates and bisphenol a on the obesity development and glucose metabolism disorders. Endocrine 55:666–681

    Article  CAS  Google Scholar 

  • Thompson RC, Moore CJ, Vom Saal FS, Swan SH (2009) Plastics, the environment and human health: current consensus and future trends. Philos Trans R Soc Lond B Biol Sci 364:2153–2166

    Article  CAS  Google Scholar 

  • Trasande L, Spanier AJ, Sathyanarayana S, Attina TM, Blustein J (2013) Urinary phthalates and increased insulin resistance in adolescents. Pediatrics, peds. 2012–4022

  • Tsatsoulis A, Mantzaris MD, Bellou S, Andrikoula M (2013) Insulin resistance: an adaptive mechanism becomes maladaptive in the current environment—an evolutionary perspective. Metabolism 62:622–633

    Article  CAS  Google Scholar 

  • Ventrice P, Ventrice D, Russo E, De Sarro G (2013) Phthalates: European regulation, chemistry, pharmacokinetic and related toxicity. Environ Toxicol Pharmacol 36:88–96

    Article  CAS  Google Scholar 

  • Zarean M, Keikha M, Poursafa P, Khalighinejad P, Amin M, Kelishadi R (2016) A systematic review on the adverse health effects of di-2-ethylhexyl phthalate. Environ Sci Pollut Res 23:24642–24693

    Article  CAS  Google Scholar 

  • Zarean M, Poursafa P, Amin MM, Kelishadi R (2018) Association of endocrine disrupting chemicals, bisphenol A and phthalates, with childhood obesity: a systematic review. J Pediatr Rev 6

Download references

Author information

Authors and Affiliations

  1. Environment Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran

    Bahareh Shoshtari-Yeganeh, Maryam Zarean, Parinaz Poursafa, Hakimeh Teiri, Nasim Rafiei & Bahare Dehdashti

  2. Department of Biostatistics and Epidemiology, Faculty of Health, Isfahan University of Medical Sciences, Isfahan, Iran

    Marjan Mansourian

  3. Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran

    Roya Riahi & Roya Kelishadi

Authors
  1. Bahareh Shoshtari-Yeganeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maryam Zarean
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marjan Mansourian
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Roya Riahi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Parinaz Poursafa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hakimeh Teiri
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Nasim Rafiei
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Bahare Dehdashti
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Roya Kelishadi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Parinaz Poursafa.

Additional information

Responsible editor: Philippe Garrigues

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shoshtari-Yeganeh, B., Zarean, M., Mansourian, M. et al. Systematic review and meta-analysis on the association between phthalates exposure and insulin resistance. Environ Sci Pollut Res 26, 9435–9442 (2019). https://doi.org/10.1007/s11356-019-04373-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11356-019-04373-1

Keywords

Search

Navigation