Circulating Levels of Phthalate Metabolites Are Associated With Prevalent Diabetes in the Elderly

Abstract

OBJECTIVEPhthalates are ubiquitous industrial high-volume chemicals known as ligands to peroxisome proliferator–activated receptors (PPARs). Because PPAR-γ agonists modulate insulin sensitivity and are used to treat type 2 diabetes, we investigated whether circulating levels of phthalate metabolites are related to prevalent type 2 diabetes.RESEARCH DESIGN AND METHODSA total of 1,016 subjects, aged 70 years, were investigated in the Prospective Investigation of the Vasculature in Uppsala Seniors Study. Four phthalate metabolites were detected in almost all participant sera by an API 4000 liquid chromatograph/tandem mass spectrometer. Type 2 diabetes was defined as the use of pharmacological hypoglycemic agents or a fasting plasma glucose >7.0 mmol/L.RESULTSA total of 114 subjects were shown to have diabetes. Following adjustment for sex, BMI, serum cholesterol and triglycerides, educational level, and smoking and exercise habits, high levels of the phthalate metabolites monomethyl phthalate (MMP) (P < 0.01), monoisobutyl phthalate (MiBP) (P < 0.05), and monoethyl phthalate (MEP) (P < 0.05), but not mono(2-ethylhexyl) phthalate, were associated with an increased prevalence of diabetes. Using the fasting proinsulin–to–insulin ratio as a marker of insulin secretion and the homeostasis model assessment-insulin resistance index as a marker of insulin resistance, MiBP was mainly related to poor insulin secretion, whereas MEP and MMP mainly were related to insulin resistance.CONCLUSIONSThe findings in this cross-sectional study showed that several phthalate metabolites are related to diabetes prevalence, as well as to markers of insulin secretion and resistance. These findings support the view that these commonly used chemicals might influence major factors that are regulating glucose metabolism in humans at the level of exposure of phthalate metabolites seen in the general elderly population.

Exposure to phthalates, bisphenol A and metals in pregnancy and the association with impaired glucose tolerance and gestational diabetes mellitus: The MIREC study

“…Several epidemiologic studies have found associations between exposure to bisphenol A (BPA) and diabetes (Sun et al, 2014;Lang et al, 2008;Melzer et al, 2010;Silver et al, 2011;Shankar and Teppala, 2011). Phthalates have also been associated with type 2 diabetes (Sun et al, 2014) and insulin resistance (James-Todd et al, 2012;Lind et al, 2012;Stahlhut et al, 2007) in human populations. However, there are limited epidemiologic data assessing the risk of metabolic dysfunction associated with exposure to endocrine disrupting chemicals during pregnancy (Ettinger et al, 2009;Robledo et al, 2013).…”

Aspectos epidemiológicos de la diabetes mellitus y su relación con los contaminantes ambientales

“…Estos químicos son parte de la materia prima principal en la fabricación de plástico. Existen reportes que sugieren una relación entre los ftalatos y la diabetes, obesidad y resistencia a la insulina (114). Estudios in vitro, indican que afectan la regulación del RI, la oxidación de la glucosa en células hepáticas y en general la homeostasis de la glucosa (115).…”

Stanowisko Polskiego Towarzystwa Endokrynologicznego dotyczące związków endokrynnie czynnych (EDC)

“…They could act also via PPARa and PPARa-independent pathways [30]. PAE also seem to be involved in the pathogenesis of insulin resistance [31], obesity [32], and T2DM [33].…”