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

Award Number: R01ES032247
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/08/2020
PERIOD OF PERFORMANCE END DATE: 06/30/2026

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


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2023	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90033	LOS ANGELES	USA	Environmental Health	000	4	7/23/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $456,177 )
2023	2023	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST	LOS ANGELES	CA	90089	LOS ANGELES	USA	Environmental Health	000	4	6/1/2023	NON-COMPETING CONTINUATION	$456,177
														Subtotal = $456,177

Issue Date FY: 2022 ( Subtotal = $455,352 )
2022	2022	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Environmental Health	000	3	6/24/2022	NON-COMPETING CONTINUATION	$455,352
														Subtotal = $455,352

Issue Date FY: 2021 ( Subtotal = $466,619 )
2021	2021	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Environmental Health	000	2	7/13/2021	NON-COMPETING CONTINUATION	$466,619
														Subtotal = $466,619

Issue Date FY: 2020 ( Subtotal = $490,160 )
2020	2020	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Environmental Health	000	1	9/8/2020	NEW	$490,160
														Subtotal = $490,160

Grand Total All Awards = $1,868,308

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

Award Number: R01ES032247

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/08/2020

PERIOD OF PERFORMANCE END DATE: 06/30/2026

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