Studies from several countries report increases in rates of gestational diabetes mellitus (GDM) over recent decades. Exposure to environmental chemicals could contribute to this trend. To determine the associations between plasticisers and metals measured in early pregnancy with impaired glucose tolerance (IGT) and GDM in a Canadian pregnancy cohort. Women enrolled in the Maternal-Infant Research on Environmental Chemicals (MIREC) Study were included if they had a singleton delivery and did not have pre-existing diabetes. Eleven phthalate metabolites and total bisphenol A (BPA) were measured in first-trimester urine samples, and four metals (lead, cadmium, mercury and arsenic) were measured in first-trimester blood samples. IGT and GDM were assessed in accordance with standard guidelines by chart review. Chemical concentrations were grouped by quartiles, and associations with outcomes were examined using logistic regression with adjustment for maternal age, race, pre-pregnancy BMI, and education. Restricted cubic spline analysis was performed to help assess linearity and nature of any dose-response relationships. Of 2001 women recruited into the MIREC cohort, 1274 met the inclusion criteria and had outcome data and biomonitoring data measured for at least one of the chemicals we examined. Elevated odds of GDM were observed in the highest quartile of arsenic exposure (OR = 3.7, 95% CI = 1.4-9.6) in the adjusted analyses. A significant dose-response relationship was observed in a cubic spline model between arsenic and odds of GDM (p < 0.01). No statistically significant associations were observed between phthalates or BPA or other metals with IGT or GDM. Our findings add to the growing body of evidence supporting the role of maternal arsenic exposure as a risk factor for gestational diabetes.

Given the susceptibility of the fetus to toxicants, it is important to estimate their exposure. Approximately 2000 pregnant women were recruited in 2008-2011 from 10 cities across Canada. Cd, Pb, Mn and total Hg were measured in maternal blood from the 1st and 3rd trimesters, umbilical cord blood, and infant meconium. Nutrient intakes of vitamin D, iron, and calcium (Ca) were assessed using a food frequency questionnaire and a dietary supplement questionnaire. Median concentrations in 1st trimester maternal blood (n = 1938) were 0.20, 8.79 and 0.70 μg/L for Cd, Mn and Hg, respectively, and 0.60 μg/dL for Pb. While the median difference between the paired 1st and 3rd trimester concentrations of Cd was 0, there was a significant decrease in Pb (0.04 μg/dL) and Hg (0.12 μg/L) and an increase in Mn (3.30 μg/L) concentrations over the course of the pregnancy. While Cd was rarely detected in cord blood (19%) or meconium (3%), median Pb (0.77 μg/dL), Mn (31.87 μg/L) and Hg (0.80 μg/L) concentrations in cord blood were significantly higher than in maternal blood. Significant negative associations were observed between estimated Ca intake and maternal Cd, Pb, Mn and Hg, as well as cord blood Pb. Vitamin D intake was associated with lower maternal Cd, Pb, and Mn as well as Pb in cord blood. Even at current metal exposure levels, increasing dietary Ca and vitamin D intake during pregnancy may be associated with lower maternal blood Pb and Cd concentrations and lower Pb in cord blood.

Studies comparing adipose tissue metabolism in central versus peripheral fat depots have generated equivocal data. We examined whether regional differences in abdominal subcutaneous and omental adipose tissue metabolism in women exist and whether they persist across the spectrum of body fatness and abdominal adiposity values. We measured adipocyte size; lipoprotein lipase (LPL) activity; and basal, isoproterenol-, forskolin-, and dibutyryl cAMP–stimulated lipolysis in adipose tissue or mature adipocytes isolated from the omental and subcutaneous fat depots in a sample of 55 healthy women undergoing elective gynecological surgery. Measures of body fat mass and body fat distribution were also obtained by dual-energy X-ray absorptiometry and computed tomography. Subcutaneous adipocytes were significantly larger than omental adipocytes (P < 0.0001). LPL activity expressed as a function of cell number was significantly higher in subcutaneous versus omental adipose tissue (P < 0.0001). Basal, isoproterenol-stimulated, dibutyryl cAMP–stimulated (10⁻³ mol/l) and forskolin-stimulated (10⁻⁵ mol/l) lipolysis (expressed as a function of cell number) were all significantly higher in subcutaneous versus omental adipocytes (P < 0.05 to P < 0.0001). However, the response of omental adipocytes to lipolytic stimuli tested (fold increase over basal level) was significantly greater in magnitude compared with subcutaneous adipocytes (P < 0.01). These differences were relatively constant across total body fat mass and visceral adipose tissue area tertiles. In conclusion, compared with adipocytes from the omental fat compartment, subcutaneous adipocytes are larger, have higher LPL activity, and are more lipolytic on an absolute basis, which may reflect a higher fat storage capacity in this depot in women. In contrast, omental adipocytes display greater relative responsiveness to both adrenergic receptor–and postreceptor-acting agents compared with subcutaneous adipocytes. Overall and visceral obesity have only minor effects on regional differences in adipose tissue metabolism.

Studies report increases in rates of gestational diabetes mellitus (GDM) over recent decades. Environmental chemicals may increase the risk of diabetes through impacts on glucose metabolism, mitochondrial dysfunction, and endocrine-disrupting mechanisms including effects on pancreatic β-cell function and adiponectin release. To determine the associations between pesticides, perfluoroalkyl substances (PFASs) and polychlorinated biphenyls (PCBs) measured in early pregnancy and impaired glucose tolerance (IGT) and GDM in a Canadian birth cohort. Women enrolled in the Maternal-Infant Research on Environmental Chemicals (MIREC) Study were included if they had a singleton delivery and did not have pre-existing diabetes. Exposure variables included three organophosphorus (OP) pesticide metabolites detected in first-trimester urine samples, as well as three organochlorine (OC) pesticides, three PFASs, and four PCBs in first-trimester blood samples. Gestational IGT and GDM were assessed by chart review in accordance with published guidelines. Adjusted logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CI) for the association between quartiles of environmental chemicals and both gestational IGT and GDM. Of the 2001 women recruited into the MIREC cohort, 1274 met the inclusion criteria and had outcome and biomonitoring data available. Significantly lower odds of GDM were observed in the third and fourth quartiles of dimethylphosphate (DMP) and in the fourth quartile of dimethylthiophosphate (DMTP) in adjusted analyses (DMP Q3: OR=0.2, 95% CI=0.1-0.7; DMP Q4: OR=0.3, 95% CI=0.1-0.8; DMTP: OR=0.3, 95% CI=0.1-0.9). Significantly elevated odds of gestational IGT was observed in the second quartile of perfluorohexane sulfonate (PFHxS) (OR=3.5, 95% CI=1.4-8.9). No evidence of associations with GDM or IGT during pregnancy was observed for PCBs or OC pesticides. We did not find consistent evidence for any positive associations between the chemicals we examined and GDM or IGT during pregnancy. We observed statistical evidence of inverse relationships between urine concentrations of DMP and DMTP with GDM. We cannot rule out the influence of residual confounding due to unmeasured protective factors, such as nutritional benefits from fruit and vegetable consumption, also associated with pesticide exposure, on the observed inverse associations between maternal OP pesticide metabolites and GDM. These findings require further investigation.

Organophosphate (OP) insecticides are commonly used in agriculture. Their use decreased in recent years as they were gradually replaced by other pesticides, but some OPs are still among the insecticides most used in Canada. Exposure to elevated levels of OPs during pregnancy has been associated with adverse birth outcomes and poorer neurodevelopment in children. The objective of the present study was to examine the relationship between the concentrations of OP pesticides urinary dialkyl phosphate (DAP) metabolites and various factors that are potential sources of exposure or determinants of DAP levels. In the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, six DAPs were measured in 1st trimester urine samples of 1884 pregnant women living in Canada. They were grouped into sums of dimethyl alkyl phosphates (DMAP) and diethyl alkyl phosphates (DEAP) for statistical analysis. We found that 93% of women had at least one DAP detected in their urine. Geometric means (GM) of specific gravity-corrected levels for urine dilution were 59 (95% CI 56-62) and 21 (95% CI 20-22) nmol/L for DMAP and DEAP, respectively. The following characteristics were significantly associated with higher urinary concentrations of DMAP or DEAP: higher education, nulliparous, normal pre-pregnancy body mass index, non-smoker, not fasting at sampling, winter season at sampling, and early and late day collection times. Dietary items that were significantly related with higher urinary concentrations included higher intake of citrus fruits, apple juice, sweet peppers, tomatoes, beans and dry peas, soy and rice beverages, whole grain bread, white wine and green and herbal teas. This study indicates that exposure to these compounds is quasi-ubiquitous. The factors associated with greater DAP levels identified here could be useful to regulatory agencies for risk analysis and management. However, some exposure misclassification might occur due to the single DAP measurement available, and to the presence of preformed DAPs in the environment.