Serum Phthalate and Triclosan Levels Have Opposing Associations With Risk Factors for Gestational Diabetes Mellitus

Abstract

Certain phthalates and bisphenol A (BPA) have been associated with insulin resistance and type 2 diabetes in non-pregnant adults, but studies of gestational diabetes mellitus (GDM) have reported conflicting results for phthalates and no associations with BPA. Our aim was to investigate the relationship between maternal serum levels of phthalate metabolites and phenols at 10–17 weeks of gestation and glucose homeostasis at 28 weeks of gestation. 232 women aged ≥16 years without type 1 or 2 diabetes with singleton male pregnancies were recruited from a single UK maternity centre between 2001 and 2009 as part of a prospective observational study (Cambridge Baby Growth Study). Serum levels of 16 phthalate metabolites and 9 phenols (including BPA) were measured using liquid chromatography/tandem mass spectrometry. Oral glucose tolerance tests were performed at 28 weeks. 47/232 (20.3%) women had GDM. First-trimester triclosan (TCS) was inversely associated with incident GDM (adjusted odds ratio per log increase in concentration 0.54, 95% confidence interval 0.34–0.86, p = 0.010). Amongst women without GDM, first-trimester mono-(2-ethylhexyl) phthalate and mono(carboxyisooctyl) phthalate levels were positively associated with 120-min plasma glucose (adjusted β 0.268 and 0.183, p = 0.0002 and 0.010, respectively) in mid-pregnancy. No other monotonic associations were detected between phthalate or phenol levels and fasting or stimulated plasma glucose, β-cell function, insulin resistance, or 60-min disposition index. Our results support a glycaemia-raising effect of phthalates during pregnancy, consistent with findings in non-pregnant populations and suggest a possible protective effect of exposure to TCS against GDM.

Unhealthy Levels of Phthalates and Bisphenol A in Mexican Pregnant Women with Gestational Diabetes and Its Association to Altered Expression of miRNAs Involved with Metabolic Disease

“…Our findings regarding high urinary levels of MEHP in non-diabetic women compared to GDM patients are similar to the results found in the Cambridge Baby Growth Study subcohort, where no positive associations between MEHP serum levels and GDM were found. However, positive associations between MEHP serum levels with 120-min plasma glucose in women without GDM [62] were found. In another study performed in a cohort of pregnant women in China, MEHP exposure levels were correlated with fasting blood glucose levels in the third trimester of pregnancy in non-diabetics but not in women with GDM [36].…”

The Endocrine Disruption of Prenatal Phthalate Exposure in Mother and Offspring

“…Recently, several groups assessed the effect of phthalate exposure on glycemia, hypertensive, and vitamin D homeostasis during pregnancy and hypothesized that the effect may associate with pregnancy complications, including GDM and pregnancy-induced hypertensive diseases (42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54). So it is important to characterize the potential risk of phthalate exposure during pregnancy.…”

“…It was reported that phthalate exposure led to a loss and an abnormal ultrastructural pattern of β cells in the pancreas, thereby reducing the insulin content and altering blood glucose levels (55). To date, a lot of epidemiological research had evaluated the associations between maternal phthalate exposure and gestational glycemia levels (42)(43)(44)(45)(46), but there was not enough evidence to draw a definitive conclusion.…”

“…In a cohort study ( n = 72), maternal urinary concentrations of MiBP and MBzP during the first trimester (median = 12.8 gestational weeks) were correlated to lower blood glucose levels at the time of GDM screening after adjustment for urinary creatinine, race/ethnicity, and gestational age ( 42 ). Using a prospective cohort design, Fisher et al ( 43 ) observed that a positive association between MEHP, MCiOP, and MEHP/MECPP and 120-min glucose levels measured at 28 gestational weeks and apparent non-linear correlations between MiBP exposure and higher odds of GDM. And maternal MEP exposure was positively associated with odds of GDM, which was reported by a recent larger-population study ( 44 ).…”

Bisphenol A and Phthalates in Diet: An Emerging Link with Pregnancy Complications

“…Similarly, BPA urinary levels at the second trimester of pregnancy were positively associated with post-load glycaemia levels [94]. However, other cohort studies did not confirm the association between EDCs exposure and IGT, showing contrasting results for both BPA [95][96][97][98][99] and phthalates [97]. A possible reason for these controversial outcomes lies in the confounding effect of adiposity.…”