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Elucidating Determinants of Gestational Beta-Cell Adaptation and Failure

阐明妊娠期β细胞适应和失败的决定因素

基本信息

批准号：
10166833
负责人：
Camille Elise Powe
金额：
$ 20万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-07-01 至 2023-01-15
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10166833
关键词：
Affect Area Beta Cell Biological Assay Cells Clinical Endocrinology Clinical Research Complex Data Data Analyses Defect Development Diabetes Mellitus Discipline of obstetrics Disease Doctor of Medicine Endocrine System Diseases Endocrinology Enrollment Ethics Failure Fasting Foundations Future General Hospitals General Population Genetic Genomics Gestational Diabetes Glucose Goals High Risk Woman Hormones Human Hyperglycemia Impairment In Vitro Insulin Insulin Resistance Investigation Late pregnancy Massachusetts Measures Medical Mentors Mentorship Metabolic Metabolic Diseases Methods Nephrology Non-Insulin-Dependent Diabetes Mellitus Pathway interactions Physicians Physiological Physiology Plasma Play Population Postpartum Period Postpartum Women Pregnancy Pregnancy Complications Pregnant Women Prevention Prevention strategy Program Development Proinsulin Reporter Research Research Personnel Risk Risk Factors Rodent Model Role Sampling Scientist Structure of beta Cell of islet Techniques Testing Therapeutic Training Variant Woman Work base career career development cohort cost diabetes mellitus genetics early pregnancy euglycemia experience fasting glucose genetic variant glucose metabolism high risk improved insulin secretion maternal risk novel patient oriented research perinatal morbidity perinatal outcomes pregnant programs research and development response skills trait treatment strategy

项目摘要

Elucidating Determinants of Gestational Beta-Cell Adaptation and Failure The candidate is an M.D. trained in clinical endocrinology who will undertake a five-year mentored research and career development program in the genetics, physiology, and endocrinology of glucose metabolism in pregnancy at Massachusetts General Hospital (MGH). The candidate will complete the proposed program under the mentorship of prominent researchers with complementary areas of expertise: 1) Dr. Jose C. Florez, Chief of the MGH Diabetes Unit and world-recognized leader in translational investigation of type 2 diabetes genetics and 2) Dr. Ravi Thadhani, Chief of the MGH Nephrology Division and expert in translational investigation of medical disorders in pregnancy. The candidate will undertake coursework, receive mentorship, and gain practical experience in physiologic investigation, longitudinal and genetic data analysis, advanced techniques to profile human plasma, and safe, ethical conduct of research in the obstetric population. This program will uniquely equip the candidate with the skills necessary to become an independent physician-scientist investigating endocrine and metabolic disease in pregnancy. Indeed, during pregnancy, there are profound changes in glucose metabolism. By late gestation, maternal pancreatic beta cells must dramatically increase insulin secretion in the face of marked pregnancy-induced insulin resistance. In 5-10% of pregnant women, this beta-cell adaptation fails, resulting in gestational diabetes mellitus (GDM). GDM is associated with costly adverse perinatal outcomes and a high risk of future maternal type 2 diabetes. It is unclear to what extent GDM results from maternal beta-cell defects that preceded pregnancy or from an imbalance of circulating hormones that stimulate the beta cell during gestation. The scientific goal of the proposed research is to assess the contribution of maternal genetics and circulating gestational hormones to beta-cell adaptation and failure in pregnancy. In Aim 1, the candidate will determine the primary physiologic mechanism(s) by which maternal genetic variants alter the risk of GDM. In Aim 2, the candidate will test whether the plasma of pregnant women contains endogenous beta-cell stimulatory activity which is deficient in GDM. To accomplish these aims, the candidate will study pregnant women in two cohorts: one established, with cross-sectional physiologic data and one actively enrolling, with longitudinal physiologic data. The proposed research may define key pathways leading to hyperglycemia in pregnancy which can be targeted in novel pregnancy- specific prevention and treatment strategies for GDM.

阐明妊娠期β细胞适应和失败的决定因素

项目成果

期刊论文数量（17）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Placental RNA sequencing implicates IGFBP1 in insulin sensitivity during pregnancy and in gestational diabetes.

胎盘 RNA 测序表明 IGFBP1 与妊娠期胰岛素敏感性和妊娠糖尿病有关。

DOI：
10.21203/rs.3.rs-3464151/v1
发表时间：
2023
期刊：
Research square
影响因子：
0
作者：
Hivert,Marie-France;White,Frederique;Allard,Catherine;James,Kaitlyn;Majid,Sana;Aguet,François;Ardlie,Kristin;Edlow,Andrea;Florez,Jose;Bouchard,Luigi;Jacques,Pierre-Etienne;Karumanchi,S;Powe,Camille
通讯作者：
Powe,Camille

Genetic Determinants of Glycemic Traits and the Risk of Gestational Diabetes Mellitus.

DOI：
10.2337/db18-0203
发表时间：
2018-12
期刊：
Diabetes
影响因子：
7.7
作者：
Powe CE;Nodzenski M;Talbot O;Allard C;Briggs C;Leya MV;Perron P;Bouchard L;Florez JC;Scholtens DM;Lowe WL Jr;Hivert MF
通讯作者：
Hivert MF

Genetic Loci and Physiologic Pathways Involved in Gestational Diabetes Mellitus Implicated Through Clustering.

DOI：
10.2337/db20-0772
发表时间：
2021-01
期刊：
Diabetes
影响因子：
7.7
作者：
Powe CE;Udler MS;Hsu S;Allard C;Kuang A;Manning AK;Perron P;Bouchard L;Lowe WL Jr;Scholtens D;Florez JC;Hivert MF
通讯作者：
Hivert MF

Genetic Studies of Gestational Diabetes and Glucose Metabolism in Pregnancy.