The intensifying type 2 diabetes (T2D) epidemic among minority women is a substantial threat to public health.1,2 Women with gestational diabetes mellitus (GDM) history carry a lifetime risk of progression to T2D of up to 70%.3 Therefore, GDM is a unique model for investigating T2D pathogenesis. Beyond well-known risk factors such as unhealthy lifestyle and genetic susceptibility, there is growing evidence that exposures to endocrine disrupting chemicals (EDCs), may be important and unrecognized contributors to the pathogenesis of T2D.
The broad objective of this study is to investigate the effects of exposure to persistent organic pollutants (POPs) during the vulnerable time windows of pregnancy and the postpartum period on negative metabolic trajectories involved in the pathogenesis of T2D in women after pregnancies.
Studies in the general population have shown that POPs exposure is associated with insulin resistance and lower β-cell function.4-10 Several studies in women have also found that POPs exposure during pregnancy is associated with higher risk of GDM. However, most previous studies were cross-sectional and no studies have assessed the long-term effects of POPs exposure during pregnancy and the postpartum period on the metabolic decline and development of T2D in women’s later life. Little is known about the joint effects of exposure to POPs mixture on the glucose metabolic decline and T2D risk.
To fill knowledge gaps needed to develop personalized preventive interventions, we propose to measure 60 potentially diabetogenic POPs from pregnancy to postpartum period and assess their prospective effects on the longitudinal decline of insulin sensitivity and β-cell function in women after delivery, adjusting for key confounders including breast feeding, changes in adiposity and diet (Aim 1). The study will be built upon a unique prospective cohort of 102 Hispanic women who had GDM during pregnancy and were followed from pregnancy to 12 years after delivery.
We will investigate longitudinal changes in metabolomic profiles as long-term biological response to POPs exposure during the pregnancy window and identify metabolomic signatures that predict metabolic decline and T2D incidence (Aim 2). No prospective study has been published to investigate the long-term, prospective effect of POPs exposure during pregnancy on dysregulated metabolic pathways in women.
Impact: This project will build longitudinal evidence for the long-term metabolic effects of POPs exposure in women, focusing on critical exposure windows during pregnancy and the postpartum period. Findings of this project will contribute important reference for future regulations of toxic chemicals to protect human health and reduce health disparities among minority women.
- First-of-its-kind PSA campaign targets the 86 million American adults with prediabetes. 2016. (Accessed June 13th, 2019, at http://www.diabetes.org/newsroom/press-releases/2016/first-of-its-kind-psa-campaign-targets-86-million-american-adults-with-prediabets.html.)
- Mercader JM, Florez JC. The genetic basis of type 2 diabetes in Hispanics and Latin Americans: challenges and opportunities. Front Public Health 2017;5:329.PMID: 29376044.PMC5763127.
- Kim C, Newton KM, Knopp RH. Gestational diabetes and the incidence of type 2 diabetes. Diabetes Care 2002;25:1862.PMID: 12351492.
- Cranmer M, Louie S, Kennedy RH, Kern PA, Fonseca VA. Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is associated with hyperinsulinemia and insulin resistance. Toxicological sciences : an official journal of the Society of Toxicology 2000;56:431-6.PMID: 10911003.
- Goodman M, Narayan KM, Flanders D, et al. Dose-response relationship between serum 2,3,7,8-tetrachlorodibenzo-p-dioxin and diabetes mellitus: a meta-analysis. American journal of epidemiology 2015;181:374-84.PMID: 25731889.PMC4380020.
- Magliano DJ, Loh VH, Harding JL, Botton J, Shaw JE. Persistent organic pollutants and diabetes: a review of the epidemiological evidence. Diabetes & metabolism 2014;40:1-14.PMID: 24262435.
- Lee DH, Steffes MW, Sjodin A, Jones RS, Needham LL, Jacobs DR, Jr. Low dose of some persistent organic pollutants predicts type 2 diabetes: a nested case-control study. Environ Health Perspect 2010;118:1235-42.PMID: 20444671.PMC2944083.
- Sun Q, Zong G, Valvi D, Nielsen F, Coull B, Grandjean P. Plasma concentrations of perfluoroalkyl substances and risk of type 2 diabetes: a prospective investigation among U.S. women. Environ Health Perspect 2018;126:037001.PMID: 29498927.PMC6071816.
- Cardenas A, Gold DR, Hauser R, et al. Plasma concentrations of per- and polyfluoroalkyl substances at baseline and associations with glycemic Indicators and diabetes Incidence among high-risk adults in the diabetes prevention program trial. Environ Health Perspect 2017;125:107001.PMID: 28974480.PMC5933403.
- Alderete TL, Jin R, Walker DI, et al. Perfluoroalkyl substances, metabolomic profiling, and alterations in glucose homeostasis among overweight and obese Hispanic children: A proof-of-concept analysis. Environ Int 2019;126:445-53.PMID: 30844580.PMC6555482.