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: 10653028
• 负责人: Zhanghua Chen
• 金额: $ 45.62万
• 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 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10653028
• 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; Early identification; Elderly; Endocrine Disruptors; Environment; Epidemic; Exposure to; Fasting; Flame Retardants; Functional disorder; Future; General Population; Genetic Predisposition to Disease; Gestational Diabetes; Glucose; Goals; Health; Hispanic; Human; Incidence; Individual; Insulin Resistance; International; Investigation; Joints; Knowledge; Link; Long-Term Effects; Measures; Metabolic; Metabolic Pathway; Methods; Minority Women; Modeling; Mothers; Non-Insulin-Dependent Diabetes Mellitus; OGTT; Obesity; Parents; Pathogenesis; Physical activity; Plasma; Poison; Poly-fluoroalkyl substances; Polychlorinated Biphenyls; Postpartum Period; Predisposition; Pregnancy; Pregnancy Complications; Pregnancy Trimesters; Pregnant Women; Prospective Studies; Prospective cohort; Public Health; Publishing; Recording of previous events; Reduce health disparities; 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; high risk; insulin sensitivity; interest; intravenous glucose tolerance test; lifetime risk; lipid metabolism; lipophilicity; metabolomics; novel; organochlorine pesticide; persistent organic pollutants; post pregnancy; predictive signature; prevent; preventive intervention; progression risk; 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.

抽象的 预防糖尿病已成为妊娠期糖尿病女性的国家优先事项。 (GDM) 病史在一生中患 2 型糖尿病 (T2D) 的风险显着更高。 GDM 已被用作识别早期代谢缺陷（例如胰岛素抵抗和 β 细胞）的独特模型 除了众所周知的危险因素之外，年轻女性患糖尿病之前的功能障碍。 不健康的生活方式和遗传易感性，人们越来越担心接触内分泌干扰物 持久性有机污染物 (POP) 等化学物质作为 T2D 的新风险因素。 调查女性怀孕期间接触持久性有机污染物的长期影响 以及 GDM 妊娠后导致 T2D 的代谢轨迹上的产后期。 来自动物模型和人体研究的越来越多证据表明，持久性有机污染物的暴露会对 胰岛素敏感性和 β 细胞功能会增加 T2D 风险，但之前的流行病学研究表明。 持久性有机污染物和糖尿病大多是横截面的，并且具有仅检查单个因素的影响的局限性 关于接触持久性有机污染物混合物对化学物质或化学类别的联合影响知之甚少。 重要的是，没有研究评估 POP 暴露的长期影响。 怀孕期间和产后期对女性晚年代谢下降和 T2D 发展的影响， 为了填补这些知识空白，我们建议超越其他风险因素（例如衰老和体重增加）的影响。 测量 60 种事先选择的潜在糖尿病 POPs 作为内部 POPs 的血浆浓度 该项目的总体目标是： 研究妊娠期间和妊娠后 POP 暴露对胰岛素纵向下降的长期影响 该研究将建立在女性产后的敏感性和β细胞功能以及糖尿病发病率的基础上。 一项独特的前瞻性队列，由 102 名怀孕期间患有 GDM 的女性组成，并在怀孕后进行随访 使用原始队列评估了分娩后 12 年的胰岛素敏感性和 β 细胞功能。 妊娠第 3 个月和每 15 个月进行静脉葡萄糖耐量试验的金标准方法 分娩后数月至 12 年，进一步研究 POPs 暴露与分娩之间的生物学机制。 长期代谢下降，我们将进一步研究空腹血浆的纵向代谢谱 在怀孕第三个月、产后以及长达 12 年内每 15 个月访视时收集样本。 建议使用这些代谢组学特征作为对 POPs 暴露期间的生物反应的特征 怀孕并确定那些预测代谢下降和 T2D 发病率的因素，该项目将推进我们的研究。 了解妊娠期和产后关键暴露窗口期间持久性有机污染物暴露的作用 扰乱代谢途径并诱发女性糖尿病病理生理学和 T2D 发病率的时期。