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Increased serum concentrations of persistent organic pollutants among prediabetic individuals: potential role of altered substrate oxidation patterns.

ABSTRACT: There is a need for a better understanding of the potential role of persistent organic pollutants (POPs) in the pathogenesis of type 2 diabetes.Our objective was to determine the association of serum concentrations of POPs with early signs of type 2 diabetes in regard to glucose and lipid metabolism.In this cross-sectional study, we used recent studies of 148 Danish middle-aged normoglycemic, prediabetic, and diabetic individuals examined by the euglycemic-hyperinsulinemic clamp technique with indirect calorimetry; 66 of these individuals also had an i.v. glucose tolerance test. Concentrations of POPs were analyzed in banked serum from the participants. Associations with basal and insulin-stimulated glucose and lipid metabolism were assessed after adjustment for age, sex, and body fat percentage.Individuals with prediabetes and diabetes had higher serum concentrations of several POPs compared with normoglycemic individuals. In the nondiabetic population, higher POPs levels were associated with elevated fasting plasma glucose concentrations as well as reduced glucose oxidation, elevated lipid oxidation, and elevated serum concentrations of free fatty acids (P < 0.05). We found no associations of POPs with first-phase insulin secretion, hepatic or peripheral insulin sensitivity, or nonoxidative glucose metabolism.Diabetic and prediabetic individuals have elevated serum concentrations of POPs. In nondiabetic individuals, POPs exposure is related to altered substrate oxidation patterns with lower glucose oxidation and higher lipid oxidation rates. These findings indicate that POPs may affect peripheral glucose metabolism by modifying pathways involved in substrate partitioning rather than decreasing insulin-dependent glucose uptake.

SUBMITTER: Færch K

PROVIDER: S-EPMC3431564 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Increased serum concentrations of persistent organic pollutants among prediabetic individuals: potential role of altered substrate oxidation patterns.

Færch Kristine K Højlund Kurt K Vind Birgitte F BF Vaag Allan A Dalgård Christine C Nielsen Flemming F Grandjean Philippe P

The Journal of clinical endocrinology and metabolism 20120626 9

<h4>Context</h4>There is a need for a better understanding of the potential role of persistent organic pollutants (POPs) in the pathogenesis of type 2 diabetes.<h4>Objective</h4>Our objective was to determine the association of serum concentrations of POPs with early signs of type 2 diabetes in regard to glucose and lipid metabolism.<h4>Research design and methods</h4>In this cross-sectional study, we used recent studies of 148 Danish middle-aged normoglycemic, prediabetic, and diabetic individu ...[more]

PMID: 22736774

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Project description:BackgroundPrenatal maternal plasma persistent organic pollutant (POP) concentrations have been associated with neonatal outcomes. However, the underlying mechanisms remain unknown. Placental epigenetic mechanisms may be involved, but no prior epigenome-wide studies have investigated the impact of maternal POPs on placental DNA methylation. We studied the association between maternal plasma POP concentration in early pregnancy and epigenome-wide placental DNA methylation among 260 pregnant women from the NICHD Fetal Growth Studies.ResultsOur analysis focused on POPs with more than 80% plasma concentrations above the limit of quantification, including 3 organochlorine pesticides (hexachlorobenzene, trans-nonachlor, p,p'-dichlorodiphenyldichloroethylene), 1 polybrominated diphenyl ether (PBDE 47), 3 polychlorinated biphenyls (138/158, 153, 180), and 6 poly- and perfluorinated alkyl substances (PFASs) (perfluorodecanoic acid, perfluorohexanesulfonic acid, perfluorononanoic acid, perfluorooctanesulfonic acid, perfluoroundecanoic acid (PFUnDA)). Using 5% false discovery rate, POPs were associated with a total of 214 differentially methylated CpG sites (nominal p values ranging from 2.61 × 10-21 to 2.11 × 10-7). Out of the 214 CpG sites, 24 (11%) were significantly correlated with placental expression of 21 genes. Notably, higher PFUnDA was associated with increased methylation at 3 CpG sites (cg13996963, cg12089439, cg18145877) annotated to TUSC3, and increased methylation at those 3 CpG sites was correlated with decreased expression of TUSC3 in the placenta. Increased methylation at cg18145877 (TUSC3) and decreased expression of TUSC3 were correlated with shorter birth length. Out of the 214 CpG sites, methylation at 44 CpG sites was correlated (p value < 0.10) with at least one neonatal anthropometry measure (i.e., birth weight, birth length, and head circumference). Seven CpG sites mediated (p value < 0.05) the association between PBDE 47 and neonatal anthropometry measures. Genes annotating the top differentially methylated CpG sites were enriched in pathways related to differentiation of embryonic cells (PBDE 47) and in pathways related to brain size and brain morphology (PFASs).ConclusionsDNA methylation changes in the placenta were significantly associated with maternal plasma POPs concentration. The findings suggest that placental DNA methylation and gene expression mechanism may be involved in the prenatal toxicity of POPs and their association with neonatal anthropometry measures.

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Increased serum concentrations of persistent organic pollutants among prediabetic individuals: potential role of altered substrate oxidation patterns.

Publications

Increased serum concentrations of persistent organic pollutants among prediabetic individuals: potential role of altered substrate oxidation patterns.

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