The Long-term Influence of Persistent Organic Pollutants Exposure During and After Pregnancy on Metabolic Decline in Women After Pregnancies Complicated by Gestational Diabetes

妊娠期间和妊娠后持久性有机污染物暴露对妊娠合并妊娠糖尿病女性代谢下降的长期影响

• 批准号: 10256678
• 负责人: Zhanghua Chen
• 金额: $ 46.66万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-08 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10256678
• 关键词: Adipose tissue; Affect; Aging; Amino Acids; Animal Model; Animals; Archives; Beta Cell; Biological; Biological Assay; Body Burden; Body Composition; Body fat; Breast Feeding; Cell physiology; Chemicals; Data; Defect; Development; Diabetes Mellitus; Diet; Elderly; Endocrine Disruptors; Environment; Epidemic; Exposure to; Fasting; Flame Retardants; Functional disorder; Future; General Population; Genetic Predisposition to Disease; Gestational Diabetes; Glucose; Goals; Gold; Health; Hispanics; Human; Incidence; Individual; Insulin Resistance; International; Investigation; Joints; Knowledge; Link; Long-Term Effects; Measures; Metabolic; Metabolic Pathway; Methods; Minority; Modeling; Mothers; Non-Insulin-Dependent Diabetes Mellitus; OGTT; Obesity; Parents; Pathogenesis; Physical activity; Plasma; Poison; Polychlorinated Biphenyls; Postpartum Period; Predisposition; Pregnancy; Pregnancy Trimesters; Pregnant Women; Prospective Studies; Prospective cohort; Public Health; Publishing; Recording of previous events; Regulation; Research; Risk Factors; Role; Sampling; Structure of beta Cell of islet; Third Pregnancy Trimester; Time; Visit; Weight Gain; Woman; cohort; diabetes pathogenesis; diabetes risk; diabetogenic; epidemiology study; follow-up; health disparity; high risk; insulin sensitivity; interest; intravenous glucose tolerance test; lifetime risk; lipid metabolism; lipophilicity; metabolomics; novel; organochlorine pesticide; persistent organic pollutants; predictive signature; prevent; preventive intervention; prospective; public health priorities; response; unhealthy lifestyle; young woman

ABSTRACT Preventing diabetes has become a national priority for public health. Women with gestational diabetes mellitus (GDM) history carry a significantly higher risk of developing type 2 diabetes (T2D) over their lifetime. Therefore, GDM has been used as a unique model to identify early metabolic defects such as insulin resistance and β-cell dysfunction that precede the development of diabetes in young women. Beyond well-known risk factors including unhealthy lifestyle and genetic susceptibility, there is a growing concern over exposures to endocrine disrupting chemicals, such as persistent organic pollutants (POPs), as novel risk factors for T2D. The goal of this study is to investigate long-term effects of exposure to POPs during a woman’s vulnerable time windows of pregnancy and the postpartum period on the metabolic trajectory that leads to T2D in women after GDM pregnancies. Mounting evidence from animal models and human studies suggests that POPs exposure can adversely affect insulin sensitivity and β-cell function thereby increasing T2D risk. However, previous epidemiological studies of POPs and diabetes were mostly cross-sectional and have limitations of only examining the effect of a single chemical compound or chemical class. Little is known about the joint effects of exposure to POPs mixture on the metabolic decline and T2D. Importantly, no studies have assessed the long-term effects of POPs exposure during pregnancy and postpartum period on metabolic decline and development of T2D in women’s later life, beyond the effects of other risk factors such as aging and weight gain. To fill these knowledge gaps, we propose to measure plasma concentrations of 60 priori-selected potentially diabetogenic POPs as the internal POPs exposure level in women during pregnancy and postpartum period. The broad objectives of this project are to investigate long-term effects of POPs exposure during and after pregnancy on the longitudinal decline of insulin sensitivity and β-cell function as well as diabetes incidence in women after delivery. The study will be built upon a unique prospective cohort of 102 women who had GDM during pregnancy and were followed from pregnancy to 12 years after delivery. Insulin sensitivity and β-cell function were assessed in the original cohort using the gold-standard method of intravenous glucose tolerance test at the 3rd trimester of pregnancy and every 15 months up to 12 years after delivery. To further investigate the biological mechanism linking POPs exposure and long-term metabolic decline, we will further investigate the longitudinal metabolomic profiles from fasting plasma samples collected at the 3rd trimester of pregnancy, postpartum and every 15-month visit up to 12 years. We propose to use these metabolomic profiles as signatures of the biological response to the POPs exposure during pregnancy and identify those that predict metabolic decline and T2D incidence. This project will advance our knowledge in the role of POPs exposure during critical exposure windows of pregnancy and the postpartum period in perturbing metabolic pathways and inducing diabetes pathophysiology and T2D incidence in women.

摘要