Association between urinary phthalates and metabolic abnormalities in obese Thai children and adolescents
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Tansit Saengkaew
Abstract
Background:
Several endocrine disruptors (including phthalates) are considered to be a cause of obesity. However, the current evidence has not conclusively established an association between phthalates and metabolic abnormalities, especially in children. The objective of the study was to evaluate the association between urinary phthalate metabolites and metabolic abnormalities in obese Thai children and adolescents.
Methods:
This cross-sectional case-control study was conducted in participants aged 7–18 years and divided into two groups: normal weight and overweight/obesity. Spot urine concentrations of two phthalate metabolites (monomethyl phthalate [MMP] and mono-n-buthyl phthalate [MBP]) were measured by high performance liquid chromatography (HPLC). Anthropometric data, including weight, height, body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHTR), were measured and calculated. Fasting plasma glucose, insulin, HbA1c, lipid profiles and hepatic transaminase were analyzed, and insulin resistance indices were calculated.
Results:
One hundred and fifty-five participants were included. The median MMP level in the normal weight and the overweight/obesity groups were 0 (0, 459.83) and 0 (0, 1623.50) μg/g Cr, respectively (p=0.933). The median MBP level in the normal weight and the overweight/obesity groups were 233.6 (118.1, 633.62) and 206.94 (7.4, 427.7) μg/g Cr, respectively (p=0.083). After adjusting for age, gender and puberty, there was no correlation between MBP and all anthropometric data and metabolic profiles. Participants with hypertriglyceridemia had lower MBP levels than those with normal TG level. MMP levels were not significantly different between the participants with normal and abnormal weight of all metabolic parameters.
Conclusions:
Participants with hypertriglyceridemia had lower MBP levels than those with normotriglyceridemia. However, it cannot show the correlation between phthalate and metabolic parameters.
Acknowledgments
The authors gratefully acknowledge the children and adolescents that participated in this study, their parents, and the pediatric residents and pediatric endocrinology fellows that participated in this study.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: This study was funded by a grant from the Ratchadapiseksomphot Endowment Fund of Chulalongkorn University, Bangkok, Thailand (Grant No. RA58/090).
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. de Onis M, Blossner M, Borghi E. Global prevalence and trends of overweight and obesity among preschool children. Am J Clin Nutr 2010;92:1257–64.10.3945/ajcn.2010.29786Search in Google Scholar PubMed
2. Rerksuppaphol S, Rerksuppaphol L. Prevalence of overweight and obesity among school children in uburb Thailand defined by the international obesity task force standard. J Med Assoc Thai 2010;93(2 Suppl):S27–31.Search in Google Scholar
3. Li C, Ford ES, Zhao G, Mokdad AH. Prevalence of pre-diabetes and its association with clustering of cardiometabolic risk factors and hyperinsulinemia among U.S. adolescents: National Health and Nutrition Examination Survey 2005–2006. Diabetes Care 2009;32:342–7.10.2337/dc08-1128Search in Google Scholar PubMed PubMed Central
4. Freedman DS, Khan LK, Serdula MK, Dietz WH, Srinivasan SR, et al. The relation of childhood BMI to adult adiposity: the Bogalusa Heart Study. Pediatrics 2005;115:22–7.10.1542/peds.2004-0220Search in Google Scholar PubMed
5. Freedman DS, Khan LK, Dietz WH, Srinivasan SR, Berenson GS. Relationship of childhood obesity to coronary heart disease risk factors in adulthood: the Bogalusa Heart Study. Pediatrics 2001;108:712–8.10.1542/peds.108.3.712Search in Google Scholar PubMed
6. Baillie-Hamilton PF. Chemical toxins: a hypothesis to explain the global obesity epidemic. J Altern Complement Med 2002;8:185–92.10.1089/107555302317371479Search in Google Scholar PubMed
7. Grun F, Blumberg B. Environmental obesogens: organotins and endocrine disruption via nuclear receptor signaling. Endocrinology 2006;147(6 Suppl):S50–5.10.1210/en.2005-1129Search in Google Scholar PubMed
8. Desvergne B, Feige JN, Casals-Casas C. PPAR-mediated activity of phthalates: a link to the obesity epidemic? Mol Cell Endocrinol 2009;304:43–8.10.1016/j.mce.2009.02.017Search in Google Scholar PubMed
9. Feige JN, Gerber A, Casals-Casas C, Yang Q, Winkler C, et al. The pollutant diethylhexyl phthalate regulates hepatic energy metabolism via species-specific PPARalpha-dependent mechanisms. Environ Health Perspect 2010;118:234–41.10.1289/ehp.0901217Search in Google Scholar PubMed PubMed Central
10. Barak Y, Kim S. Genetic manipulations of PPARs: effects on obesity and metabolic disease. PPAR Res 2007;2007:12781.10.1155/2007/12781Search in Google Scholar PubMed PubMed Central
11. Diamanti-Kandarakis E, Bourguignon JP, Giudice LC, Hauser R, Prins GS, et al. Endocrine-disrupting chemicals: an Endocrine Society scientific statement. Endocr Rev 2009;30:293–342.10.1210/er.2009-0002Search in Google Scholar PubMed PubMed Central
12. Kim SH, Park MJ. Phthalate exposure and childhood obesity. Ann Pediatr Endocrinol Metab 2014;19:69–75.10.6065/apem.2014.19.2.69Search in Google Scholar PubMed PubMed Central
13. Zhang Y, Meng X, Chen L, Li D, Zhao L, et al. Age and sex-specific relationships between phthalate exposures and obesity in Chinese children at puberty. PloS one 2014;9:e104852.10.1371/journal.pone.0104852Search in Google Scholar PubMed PubMed Central
14. Trasande L, Attina TM, Sathyanarayana S, Spanier AJ, Blustein J. Race/ethnicity-specific associations of urinary phthalates with childhood body mass in a nationally representative sample. Environ Health Perspect 2013;121:501–6.10.1289/ehp.1205526Search in Google Scholar PubMed PubMed Central
15. Trasande L, Spanier AJ, Sathyanarayana S, Attina TM, Blustein J. Urinary phthalates and increased insulin resistance in adolescents. Pediatrics 2013;132:e646–55.10.1542/peds.2012-4022Search in Google Scholar PubMed PubMed Central
16. Rengarajan S, Parthasarathy C, Anitha M, Balasubramanian K. Diethylhexyl phthalate impairs insulin binding and glucose oxidation in Chang liver cells. Toxicol In Vitro 2007;21:99–102.10.1016/j.tiv.2006.07.005Search in Google Scholar PubMed
17. Lin Y, Wei J, Li Y, Chen J, Zhou Z, et al. Developmental exposure to di(2-ethylhexyl) phthalate impairs endocrine pancreas and leads to long-term adverse effects on glucose homeostasis in the rat. Am J Physiol Endocrinol Metab 2011;301:E527–38.10.1152/ajpendo.00233.2011Search in Google Scholar PubMed
18. Rajesh P, Balasubramanian K. Di(2-ethylhexyl)phthalate exposure impairs insulin receptor and glucose transporter 4 gene expression in L6 myotubes. Hum Exp Toxicol 2014;33:685–700.10.1177/0960327113506238Search in Google Scholar PubMed
19. Rajesh P, Sathish S, Srinivasan C, Selvaraj J, Balasubramanian K. Phthalate is associated with insulin resistance in adipose tissue of male rat: role of antioxidant vitamins. J Cell Biochem 2013;114:558–69.10.1002/jcb.24399Search in Google Scholar PubMed
20. Lind PM, Zethelius B, Lind L. Circulating levels of phthalate metabolites are associated with prevalent diabetes in the elderly. Diabetes Care 2012;35:1519–24.10.2337/dc11-2396Search in Google Scholar PubMed PubMed Central
21. Teitelbaum SL, Mervish N, Moshier EL, Vangeepuram N, Galvez MP, et al. Associations between phthalate metabolite urinary concentrations and body size measures in New York City children. Environ Res 2012;112:186–93.10.1016/j.envres.2011.12.006Search in Google Scholar PubMed PubMed Central
22. Wang H, Zhou Y, Tang C, He Y, Wu J, et al. Urinary phthalate metabolites are associated with body mass index and waist circumference in Chinese school children. PLoS One 2013;8:e56800.10.1371/journal.pone.0056800Search in Google Scholar PubMed PubMed Central
23. Smerieri A, Testa C, Lazzeroni P, Nuti F, Grossi E, et al. Di-(2-ethylhexyl) phthalate metabolites in urine show age-related changes and associations with adiposity and parameters of insulin sensitivity in childhood. PLoS One 2015;10:e0117831.10.1371/journal.pone.0117831Search in Google Scholar PubMed PubMed Central
24. Watkins DJ, Eliot M, Sathyanarayana S, Calafat AM, Yolton K, et al. Variability and predictors of urinary concentrations of phthalate metabolites during early childhood. Environ Sci Technol 2014;48:8881–90.10.1021/es501744vSearch in Google Scholar PubMed PubMed Central
25. Jaruratanasirikul S, Kreetapirom P, Tassanakijpanich N, Sriplung H. Reliability of pubertal maturation self-assessment in a school-based survey. J Pediatr Endocrinol Metab 2015;28:367–74.10.1515/jpem-2014-0053Search in Google Scholar PubMed
26. de Onis M, Onyango AW, Borghi E, Siyam A, Nishida C, et al. Development of a WHO growth reference for school-aged children and adolescents. Bull World Health Organ 2007;85:660–7.10.2471/BLT.07.043497Search in Google Scholar PubMed PubMed Central
27. de Onis M, Lobstein T. Defining obesity risk status in the general childhood population: which cut-offs should we use? Int J Pediatr Obes 2010;5:458–60.10.3109/17477161003615583Search in Google Scholar PubMed
28. Maher V, O’Dowd M, Carey M, Markham C, Byrne A, et al. Association of central obesity with early Carotid intima-media thickening is independent of that from other risk factors. Int J Obes (Lond) 2009;33:136–43.10.1038/ijo.2008.254Search in Google Scholar PubMed
29. American Diabetes A. (2) Classification and diagnosis of diabetes. Diabetes Care 2015;38(Suppl):S8–16.10.2337/dc15-S005Search in Google Scholar PubMed
30. Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents; National Heart, Lung, and Blood Institute. Expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents: summary report. Pediatrics 2011;128(Suppl 5):S213–56.10.1542/peds.2009-2107CSearch in Google Scholar PubMed PubMed Central
31. Schwimmer JB, Dunn W, Norman GJ, Pardee PE, Middleton MS, et al. SAFETY study: alanine aminotransferase cutoff values are set too high for reliable detection of pediatric chronic liver disease. Gastroenterology 2010;138:1357–64, 64 e1–2.10.1053/j.gastro.2009.12.052Search in Google Scholar PubMed PubMed Central
32. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28:412–9.10.1007/BF00280883Search in Google Scholar
33. Singh B, Saxena A. Surrogate markers of insulin resistance: a review. World J Diabetes 2010;1:36–47.10.4239/wjd.v1.i2.36Search in Google Scholar
34. Yaghjyan L, Sites S, Ruan Y, Chang SH. Associations of urinary phthalates with body mass index, waist circumference and serum lipids among females: National Health and Nutrition Examination Survey 1999–2004. Int J Obes 2015;39:994–1000.10.1038/ijo.2015.8Search in Google Scholar
35. Bell FP. Effects of phthalate esters on lipid metabolism in various tissues, cells and organelles in mammals. Environ Health Perspect 1982;45:41–50.10.1289/ehp.824541Search in Google Scholar
36. Buang Y. The metabolic effects of di (2-ethyl hexyl) phthalate medium dose on lipid profiles in serum and liver tissue. Med J Indones 2011;20:20–6.Search in Google Scholar
37. Yanagita T, Satoh M, Enomoto N, Sugano M. Di(2-ethylhexyl)phthalate enhances hepatic phospholipid synthesis in rats. Biochim Biophys Acta 1987;919:64–70.10.1016/0005-2760(87)90218-9Search in Google Scholar
38. Gao CJ, Liu LY, Ma WL, Ren NQ, Guo Y, et al. Phthalate metabolites in urine of Chinese young adults: concentration, profile, exposure and cumulative risk assessment. Sci Total Environ 2016;543:19–27.10.1016/j.scitotenv.2015.11.005Search in Google Scholar PubMed
©2017 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Original Articles
- Standard body mass index reference data of prepubescent diabetic Egyptian children
- Frequency and risk factors of depression in type 1 diabetes in a developing country
- Association of obesity and health related quality of life in Iranian children and adolescents: the Weight Disorders Survey of the CASPIAN-IV study
- Association between urinary phthalates and metabolic abnormalities in obese Thai children and adolescents
- A pilot study of the effect of human breast milk on urinary metabolome analysis in infants
- Assessment of the correlation between the atherogenic index of plasma and cardiometabolic risk factors in children and adolescents: might it be superior to the TG/HDL-C ratio?
- Cardiovascular and metabolic risk in pediatric patients with congenital adrenal hyperplasia due to 21 hydroxylase deficiency
- Application of povidone-iodine at delivery significantly increases maternal urinary iodine but not neonatal thyrotropin in an area with iodine sufficiency
- Influence of topical iodine-containing antiseptics used during delivery on recall rate of congenital hypothyroidism screening program
- Applying targeted next generation sequencing to dried blood spot specimens from suspicious cases identified by tandem mass spectrometry-based newborn screening
- Short Communication
- Initial patient choice of a growth hormone device improves child and adolescent adherence to and therapeutic effects of growth hormone replacement therapy
- Case Reports
- An occult ectopic parathyroid adenoma in a pediatric patient: a case report and management algorithm
- Fetal goitrous hypothyroidism treated by intra-amniotic levothyroxine administration: case report and review of the literature
- Carotid intima media thickness in a girl with sitosterolemia carrying a homozygous mutation in the ABCG5 gene
- Sirolimus in the treatment of three infants with diffuse congenital hyperinsulinism
Articles in the same Issue
- Frontmatter
- Original Articles
- Standard body mass index reference data of prepubescent diabetic Egyptian children
- Frequency and risk factors of depression in type 1 diabetes in a developing country
- Association of obesity and health related quality of life in Iranian children and adolescents: the Weight Disorders Survey of the CASPIAN-IV study
- Association between urinary phthalates and metabolic abnormalities in obese Thai children and adolescents
- A pilot study of the effect of human breast milk on urinary metabolome analysis in infants
- Assessment of the correlation between the atherogenic index of plasma and cardiometabolic risk factors in children and adolescents: might it be superior to the TG/HDL-C ratio?
- Cardiovascular and metabolic risk in pediatric patients with congenital adrenal hyperplasia due to 21 hydroxylase deficiency
- Application of povidone-iodine at delivery significantly increases maternal urinary iodine but not neonatal thyrotropin in an area with iodine sufficiency
- Influence of topical iodine-containing antiseptics used during delivery on recall rate of congenital hypothyroidism screening program
- Applying targeted next generation sequencing to dried blood spot specimens from suspicious cases identified by tandem mass spectrometry-based newborn screening
- Short Communication
- Initial patient choice of a growth hormone device improves child and adolescent adherence to and therapeutic effects of growth hormone replacement therapy
- Case Reports
- An occult ectopic parathyroid adenoma in a pediatric patient: a case report and management algorithm
- Fetal goitrous hypothyroidism treated by intra-amniotic levothyroxine administration: case report and review of the literature
- Carotid intima media thickness in a girl with sitosterolemia carrying a homozygous mutation in the ABCG5 gene
- Sirolimus in the treatment of three infants with diffuse congenital hyperinsulinism
