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Circulating levels of phthalate metabolites are associated with prevalent diabetes in the elderly.

Abstract

OBJECTIVE
Phthalates 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 METHODS
A 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.
RESULTS
A 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.
CONCLUSIONS
The 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.

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  • Authors

    Lind PM, Zethelius B, Lind L

    Institution

    Department of Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden. monica.lind@medsci.uu.se

    Source

    Diabetes care 35:7 2012 Jul pg 1519-24

    MeSH

    Aged
    Cross-Sectional Studies
    Diabetes Mellitus, Type 2
    Environmental Exposure
    Female
    Homeostasis
    Humans
    Insulin
    Insulin Resistance
    Male
    Models, Biological
    Phthalic Acids
    Prevalence
    Proinsulin

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    22498808