TY - JOUR
T1 - Diethylhexyl phthalates is associated with insulin resistance via oxidative stress in the elderly
T2 - a panel study
AU - Kim, Jin Hee
AU - Park, Hye Yin
AU - Bae, Sanghyuk
AU - Lim, Youn-Hee
AU - Hong, Yun-Chul
PY - 2013
Y1 - 2013
N2 - 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. 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. 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). 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.
AB - 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. 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. 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). 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.
KW - Aged
KW - Aged, 80 and over
KW - Aging
KW - Blood Glucose/metabolism
KW - Dibutyl Phthalate/metabolism
KW - Diethylhexyl Phthalate/metabolism
KW - Environmental Pollutants/metabolism
KW - Fasting
KW - Female
KW - Humans
KW - Insulin/blood
KW - Insulin Resistance
KW - Male
KW - Malondialdehyde/urine
KW - Middle Aged
KW - Oxidative Stress
KW - Phthalic Acids/metabolism
KW - Regression Analysis
KW - Sex Factors
U2 - 10.1371/journal.pone.0071392
DO - 10.1371/journal.pone.0071392
M3 - Journal article
C2 - 23977034
SN - 1932-6203
VL - 8
SP - e71392
JO - PLoS Computational Biology
JF - PLoS Computational Biology
IS - 8
ER -
