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Phthalates, Gestational Diabetes, and Markers of Type 2 Diabetes Risk in Women

邻苯二甲酸盐、妊娠期糖尿病和女性 2 型糖尿病风险标志物

基本信息

批准号：
10058771
负责人：
Tamarra M James-Todd
金额：
$ 40.66万
依托单位：
HARVARD SCHOOL OF PUBLIC HEALTH
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-02 至 2022-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10058771
关键词：
Awareness Binding Biological Markers Blood Glucose Body Size Case Study Chemical Exposure Chemicals Cohort Studies Cosmetics Cross-Sectional Studies Data Development Diagnosis Diet Endocrine Disruptors Environment Environmental Risk Factor Epidemic Epidemiology Exposure to Fasting First Pregnancy Trimester Follow-Up Studies Food Packaging Future Genes Gestational Diabetes Glucose Glycosylated hemoglobin A Hormones Hour Human Insulin Life Style Literature Longitudinal Studies Measures Nested Case-Control Study Non-Insulin-Dependent Diabetes Mellitus Nuclear Receptors OGTT PPAR alpha Pathway interactions Plastics Population Postpartum Period Postpartum Women Pregnancy Prevalence Recording of previous events Research Research Design Risk Risk Factors Role Second Pregnancy Trimester Serum Somatotype Suggestion Targeted Research Testing Time United Nations Weight Woman World Health Organization adverse pregnancy outcome base cohort consumer product design diabetes risk epidemiologic data gestational weight gain glucose metabolism high risk impaired glucose tolerance lifestyle factors modifiable risk phthalates prepregnancy programs public health relevance receptor recruit secondary analysis study population urinary

项目摘要

DESCRIPTION (provided by applicant): Over the past several decades, the prevalence of gestational diabetes (GDM) has increased 3-fold, with implications for the growing type 2 diabetes (T2DM) epidemic among women with a history of this condition. An increasing body of literature suggests that phthalates, an endocrine disrupting chemical, are associated with increased T2DM risk in non-pregnant women. These chemicals are used in plastics, food packaging, cosmetics, and other consumer products. Phthalates bind to the nuclear receptors, peroxisome proliferator activated receptors (PPAR) alpha and gamma, which may modulate target genes that regulate glucose metabolism. While phthalates have been found to be associated with T2DM risk among non-pregnant women, it remains unclear whether these chemicals are associated with GDM risk. Preliminary data from our research suggest associations between urinary levels of mono-benzyl (MBzP) and mono-(3-carboxypropyl) (MCPP) phthalates and pregnancy-related risk factors of GDM, such as increased pre-pregnancy weight, excessive gestational weight gain, and elevated blood glucose levels during pregnancy among a subset of women (n=350) participating in an ongoing pregnancy cohort study of 4,000 women. Yet, no studies have assessed the association between phthalate levels and GDM risk. In addition, GDM is known to substantially increase future development of T2DM, with over 50% of women with a history of GDM going on to develop T2DM. This increased risk can be seen as early as 6-weeks postpartum, with women with higher fasting and 2-hour blood glucose levels being at substantially higher risk of developing T2DM in the future. However, no studies have evaluated the association between phthalate levels during and after pregnancy to determine whether these chemicals contribute to an increased risk of sustained glucose dysregulation after pregnancy. To this end, we propose conducting a nested case-control study in an established pregnancy cohort to assess the association between 1st and 2nd trimester urinary metabolite levels of mono-benzyl phthalate and mono-(3-carboxypropyl) phthalate and GDM risk, as well as biomarkers associated with GDM risk (i.e. blood glucose levels) among 560 women. We will also conduct a post-pregnancy follow-up study in 866 newly recruited women, including those with GDM, impaired glucose tolerance, and normal glycemia, to evaluate the association of higher pregnancy and post-pregnancy levels of MBzP and MCPP and post-pregnancy glucose, insulin, hemoglobin A1c, and HOMA-IR levels at 6-weeks postpartum as measures of sustained glucose dysregulation after pregnancy. By evaluating the role of phthalate levels and diabetes risk at two sensitive time points-pregnancy and the postpartum, this research will give better understanding for the role of these highly-prevalent endocrine disrupting chemicals on GDM and future T2DM risk, with implications for identifying modifiable risk factors.

描述（由申请人提供）：在过去的几十年里，妊娠糖尿病 (GDM) 的患病率增加了 3 倍，这对有该病史的女性中 2 型糖尿病 (T2DM) 的流行率不断增长产生了影响。越来越多的文献表明，邻苯二甲酸盐（一种内分泌干扰化学物质）与非孕妇 T2DM 风险增加有关。这些化学品用于塑料、食品包装、化妆品和其他消费品。邻苯二甲酸盐与核受体、过氧化物酶体增殖物激活受体 (PPAR) α 和 γ 结合，可能调节调节葡萄糖代谢的靶基因。虽然邻苯二甲酸盐已被发现与非孕妇 T2DM 风险相关，但尚不清楚这些化学物质是否与 GDM 风险相关。我们研究的初步数据表明，尿液中邻苯二甲酸单苄酯 (MBzP) 和单 (3-羧丙基) (MCPP) 的水平与 GDM 的妊娠相关危险因素之间存在关联，例如，在参与一项正在进行的妊娠队列研究的一部分女性 (n=350) 中，这些危险因素包括孕前体重增加、妊娠期体重增加过多以及怀孕期间血糖水平升高。 4,000 名女性。然而，尚无研究评估邻苯二甲酸盐水平与 GDM 风险之间的关联。此外，众所周知，GDM 会大大增加未来 T2DM 的发展，超过 50% 有 GDM 病史的女性会继续发展为 T2DM。这种风险的增加早在产后 6 周就可见一斑，空腹和 2 小时血糖水平较高的女性未来患 T2DM 的风险显着更高。然而，尚无研究评估怀孕期间和怀孕后邻苯二甲酸盐水平之间的关联，以确定这些化学物质是否会增加怀孕后持续血糖失调的风险。为此，我们建议在已建立的妊娠队列中进行一项巢式病例对照研究，以评估 560 名女性中妊娠第一和第二个月的尿代谢物邻苯二甲酸单苄酯和邻苯二甲酸单（3-羧丙基）酯水平与 GDM 风险之间的关联，以及与 GDM 风险相关的生物标志物（即血糖水平）。我们还将对 866 名新招募的女性（包括患有 GDM、糖耐量受损和血糖正常的女性）进行孕后随访研究，以评估妊娠和妊娠后较高的 MBzP 和 MCPP 水平与产后 6 周的妊娠后血糖、胰岛素、血红蛋白 A1c 和 HOMA-IR 水平之间的关系，作为持续性指标怀孕后血糖失调。通过评估邻苯二甲酸盐水平和糖尿病风险在怀孕和产后两个敏感时间点的作用，这项研究将更好地了解这些高度流行的内分泌干扰化学物质对 GDM 和未来 T2DM 风险的作用，并对识别可改变的风险因素具有重要意义。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A prospective study of early pregnancy essential metal(loid)s and glucose levels late in the second trimester.

DOI：
10.1210/jc.2019-00109
发表时间：
2019-10
期刊：
The Journal of clinical endocrinology and metabolism
影响因子：
0
作者：
Yinnan Zheng;Cuilin Zhang;M. Weisskopf;Paige L. Williams;P. Parsons;C. Palmer;G. B. Buck Louis;T. James-Todd
通讯作者：
Yinnan Zheng;Cuilin Zhang;M. Weisskopf;Paige L. Williams;P. Parsons;C. Palmer;G. B. Buck Louis;T. James-Todd

Time-specific placental growth factor (PlGF) across pregnancy and infant birth weight in women with preexisting diabetes.

患有糖尿病的女性在怀孕和婴儿出生体重期间的时间特异性胎盘生长因子（PlGF）。