Diethylhexyl Phthalates Is Associated with Insulin Resistance via Oxidative Stress in the Elderly: A Panel Study

Abstract

BackgroundInsulin 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.MethodsWe 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.ResultsThe 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).ConclusionsOur 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.

Association between phthalate exposure and lower handgrip strength in an elderly population: a repeated-measures study

“…Geometric means of MEOHP, MEHHP, and MnBP at enrollment were 15.48 μg/L, 21.11 μg/L, and 28.23 μg/L, respectively (see Additional file 1: Table S2), which are comparable to previously reported levels in the Republic of Korea [6, 7], but higher than those in the United States [26]. The levels of each phthalate metabolite were correlated at multiple time points (see Additional file 1: Table S3).…”

Urinary Phthalate Metabolites and Biomarkers of Oxidative Stress in a Mexican-American Cohort: Variability in Early and Late Pregnancy

“…Previously, positive relationships were found between biomarkers of oxidative stress, including 8-isoprostane, malondialdehyde (MDA) and 8-oxo-2 1 -deoxyguanosine (8-oxo-dG), with phthalate metabolite concentrations [4,26,32,75]. In our cohort, at 13 weeks of pregnancy, only two HMW metabolites (MCOP and MCNP) were significantly associated with 8-isoprostane.…”

Environmental Endocrine Disruption of Energy Metabolism and Cardiovascular Risk

“…DDE) as well as various PCB congeners, positively associate with obesity, abdominal adiposity, and components of the metabolic syndrome [15,27,28,29]. Phthalates are used in the plastics industry as well as in various consumer goods and medical devices [30], and phthalate metabolites have been associated with insulin resistance and abdominal obesity [31,32]. Insulin resistance has also been shown to correlate with urinary concentrations of BPA [33] and serum dioxin levels [34].…”

“…A recent epidemiological study showed that urinary phthalate (e.g. DEHP) levels correlated with levels of the oxidative stress marker malondialdehyde [32], further suggesting this mechanism as relevant for EDC-mediated atherosclerotic disease. Uptake of oxidized LDL by endothelial cells has been shown to be up-regulated by arsenic [139]; whether arsenic has similar effects in promoting macrophage foam cell formation, however, requires further study.…”