title: Diethylhexyl phthalates is associated with insulin resistance via oxidative stress in the elderly: a panel study.
abstract: BACKGROUND
  Insulin resistance (IR) is believed to be the underlying mechanism of metabolic syndrome and type 2 diabetes mellitus (DM). Recently, a few studies have demonstrated that phthalates could cause oxidative stress which would contribute to the development of IR. Therefore, we evaluated whether exposure to phthalates affects IR, and oxidative stress is involved in the phthalates-IR pathway.
  
  
  METHODS
  We recruited 560 elderly participants, and obtained blood and urine samples during repeated medical examinations. For the determination of phthalate exposure, we measured urinary levels of mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) as metabolites of diethylhexyl phthalates (DEHP), and mono-n-butyl phthalate (MnBP) as a metabolite of di-butyl phthalate (DBP). Malondialdehyde (MDA), an oxidative stress biomarker, was also measured in urine samples. We measured serum levels of fasting glucose and insulin, and derived the homeostatic model assessment (HOMA) index to assess IR. A mixed-effect model and penalized regression spline were used to estimate the associations among phthalate metabolites, MDA, and IR.
  
  
  RESULTS
  The molar sum of MEHHP and MEOHP (∑DEHP) were significantly associated with HOMA (β = 0.26, P = 0.040), and the association was apparent among participants with a history of DM (β = 0.88, P = 0.037) and among females (β = 0.30, P = 0.022). However, the relation between MnBP and HOMA was not found. When we evaluated whether oxidative stress is involved in increases of HOMA by ∑DEHP, MDA levels were significantly associated with increases of ∑DEHP (β = 0.11, P<0.001) and HOMA (β = 0.49, P = 0.049).
  
  
  CONCLUSIONS
  Our study results suggest that exposure to DEHP in the elderly population increases IR, which is related with oxidative stress, and that participants with a history of DM and females are more susceptible to DEHP exposure.
authors: Institute of Environmental Medicine, Seoul National University Medical Research Center, Seoul, Republic of Korea ; Environmental Health Center, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors: Jin Hee
authors: JH
authors: Kim
authors: Hye Yin
authors: HY
authors: Park
authors: Sanghyuk
authors: S
authors: Bae
authors: Youn-Hee
authors: YH
authors: Lim
authors: Yun-Chul
authors: YC
authors: Hong
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D001786:Blood Glucose / Q000378:metabolism; D003993:Dibutyl Phthalate / Q000378:metabolism; D004051:Diethylhexyl Phthalate / Q000378:metabolism*; D004785:Environmental Pollutants / Q000378:metabolism*; D005215:Fasting; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D008315:Malondialdehyde / Q000652:urine; D008875:Middle Aged; D018384:Oxidative Stress; D010795:Phthalic Acids / Q000378:metabolism / Q000652:urine*; D012044:Regression Analysis; D012737:Sex Factors
chemical_list: D001786:Blood Glucose; D004785:Environmental Pollutants; D007328:Insulin; D010795:Phthalic Acids; C479069:mono(2-ethyl-5-hydroxyhexyl) phthalate; D003993:Dibutyl Phthalate; C080276:mono(2-ethyl-5-oxohexyl)phthalate; D008315:Malondialdehyde; D004051:Diethylhexyl Phthalate; C028577:monobutyl phthalate
references: Am J Cardiol. 2002 Sep 5;90(5A):11G-18G
references: 12231074
references: Minerva Cardioangiol. 2006 Apr;54(2):195-214
references: 16778752
references: Arch Toxicol. 2004 Mar;78(3):123-30
references: 14576974
references: Environ Health Perspect. 2004 Mar;112(3):331-8
references: 14998749
references: Cell Metab. 2007 Oct;6(4):280-93
references: 17908557
references: Biomarkers. 2006 Jan-Feb;11(1):1-13
references: 16484133
references: Environ Health Perspect. 2004 Apr;112(5):571-4
references: 15064163
references: Toxicology. 2006 Sep 21;226(2-3):90-8
references: 16905236
references: J Chromatogr. 1974 Jul 17;94(0):209-18
references: 4844611
references: Environ Health Perspect. 2004 Dec;112(17):1734-40
references: 15579421
references: Int J Hyg Environ Health. 2005;208(4):247-53
references: 16078638
references: Ann N Y Acad Sci. 2010 Jul;1201:166-76
references: 20649553
references: Environ Res. 2011 Aug;111(6):792-6
references: 21696718
references: Mol Nutr Food Res. 2007 Jul;51(7):899-911
references: 17604388
references: Toxicol Lett. 2012 Nov 15;214(3):263-7
references: 22982457
references: Science. 2002 Apr 26;296(5568):686-9
references: 11976439
references: Arch Physiol Biochem. 2008 Oct;114(4):287-98
references: 18946789
references: Int J Androl. 2006 Feb;29(1):134-9; discussion 181-5
references: 16466533
references: Environ Health Perspect. 2002 May;110(5):515-8
references: 12003755
references: Toxicology. 2010 May 27;271(3):73-82
references: 20371260
references: Reprod Toxicol. 2004 Jan-Feb;18(1):1-22
references: 15013060
references: Bull Environ Contam Toxicol. 2004 Jun;72(6):1226-31
references: 15362453
references: Environ Health Perspect. 2008 Apr;116(4):467-73
references: 18414628
references: Regul Toxicol Pharmacol. 2006 Jul;45(2):169-77
references: 16750591
references: Environ Health Perspect. 2007 Jun;115(6):876-82
references: 17589594
references: Environ Sci Technol. 2003 Oct 15;37(20):4543-53
references: 14594359
references: Diabetes. 2005 Feb;54(2):311-21
references: 15677487
references: Endocrinol Metab Clin North Am. 2008 Dec;37(4):841-56
references: 19026935
references: Indoor Air. 2004 Jun;14(3):188-95
references: 15104786
references: J Chromatogr B Analyt Technol Biomed Life Sci. 2005 Feb 25;816(1-2):269-80
references: 15664359
references: FEBS Lett. 2007 Jul 31;581(19):3734-42
references: 17628546
references: Eur Respir J Suppl. 2003 May;40:34s-38s
references: 12762572
references: Int J Hyg Environ Health. 2004 Oct;207(5):409-17
references: 15575555
references: Environ Health Perspect. 2001 Mar;109(3):229-37
references: 11333183
references: Hum Reprod. 2003 Jul;18(7):1383-94
references: 12832361
references: Reprod Toxicol. 2005 Mar-Apr;19(4):505-15
references: 15749265
references: Biochim Biophys Acta. 2009 Feb;1792(2):83-92
references: 19041393
references: Environ Health Perspect. 2012 Sep;120(9):1307-13
references: 22796563
references: Risk Anal. 2006 Jun;26(3):803-24
references: 16834635
references: Radiat Prot Dosimetry. 2009 Jun;134(3-4):143-51
references: 19398444
references: Environ Res. 2008 Feb;106(2):257-69
references: 17976571
references: Environ Health Perspect. 2003 Jul;111(9):1148-51
references: 12842765
references: Diabetes Care. 2012 Jul;35(7):1519-24
references: 22498808
references: Int J Clin Pract. 2008 Jul;62(7):1087-95
references: 18489578
references: J Nutr Biochem. 2008 Aug;19(8):491-504
references: 17855068
references: J Cardiometab Syndr. 2007 Fall;2(4):276-82
references: 18059211
references: Int J Androl. 2006 Feb;29(1):140-7; discussion 181-5
references: 16102138
references: Toxicol Lett. 2009 Jan 30;184(2):139-44
references: 19049859
references: Environ Health Perspect. 2005 Aug;113(8):1056-61
references: 16079079
references: Environ Health Perspect. 2012 Oct;120(10):1378-84
references: 22732554
references: Occup Environ Med. 2005 Nov;62(11):806-18
references: 16234408
references: Free Radic Biol Med. 1990;9(6):515-40
references: 2079232
references: Diabetologia. 1985 Jul;28(7):412-9
references: 3899825
references: J Agric Food Chem. 1975 Sep-Oct;23(5):854-8
references: 1159183