Background: Endocrine disrupting chemicals (EDCs), such as phthalates and bisphenol A (BPA), have been associated with insulin resistance (IR) and type 2 diabetes (T2D) in non-pregnant adults. By contrast, recent pilot studies of pregnant women found negative associations between phthalates and blood glucose, and a lack of association with BPA. No studies have examined gestational IR or secretion in relation to EDC exposure.
Objective: To confirm these results and explore associations with IR and secretion.
Methods: 259 mothers without T1D/T2D with singleton male pregnancies were recruited as part of larger prospective study (Cambridge Baby Growth Study). Serum was collected at 10-12 weeks gestation. 27 EDCs (16 phthalate monoesters, 9 phenols) were measured using liquid chromatography/tandem mass spectrometry. Summed levels were calculated for di(2-ethylhexyl)phthalate metabolites (ΣDEHPm) and all phthalate metabolites (Σall.phth.m). Gestational diabetes mellitus (GDM) was diagnosed from an oral glucose tolerance test at 28 weeks gestation using WHO criteria. Homeostasis Model Assessment (HOMA)-IR and β-cell function were calculated. Regressions controlled for age, body mass index (BMI), deprivation index, ethnicity, smoking, and parity.
Results: Six phthalates (MEP, MiBP, MnBP, MEHP, MECPP, MCiOP) and three phenols (BPA, TCS, BP-3) were detectable in >60% samples. Demographic variables and EDC levels did not differ between women with (n=47) and without GDM. Compared to quartile 1, Σall.phth.m quartile 3 alone was associated with decreased odds of GDM [adjusted-OR (95%CI) 0.13 (0.03-0.56), Ptrend=0.037]; no other EDCs were associated with GDM in continuous or quartile analyses. ΣDEHPm (adjusted-β=0.241, P=0.004) and Σall.phth.m (adjusted-β=0.254, P=0.001) were positively associated with 2-h blood glucose. No EDCs were associated with HOMA-IR, HOMA-β-cell function, or disposition index.
Conclusion: Serum phthalate levels were associated with stimulated blood glucose levels. Their association with GDM risk suggests a non-monotonic dose-response relationship. EDC exposure was not associated with perturbations of gestational IR or secretion.
Funding information: This work was supported by a European Union Framework V programme, the World Cancer Research Fund International, the Medical Research Council (UK), the Newlife Foundation, the Evelyn Trust, and the NIHR (National Institute for Health Research) Cambridge Biomedical Research Centre.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology