Metabolite Profiles Preceding Progression to Diabetes Mellitus after Gestational Diabetes

妊娠糖尿病后进展为糖尿病之前的代谢特征

基本信息

批准号：
10398839
负责人：
Erica Pauline Gunderson
金额：
$ 60.68万
依托单位：
KAISER FOUNDATION RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-01 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10398839
关键词：
Address Adult Age Asian Biochemical Markers Biological Assay Biological Markers Black race Blood Blood Glucose Caring Classification Clinical Communities Consumption Defect Deterioration Diabetes Mellitus Diabetes prevention Disease Effectiveness Electronic Health Record Enrollment Erythrocytes Ethnic Origin Ethnic Population European ancestry Fasting Functional disorder Future Gestational Diabetes Glucose Glycosylated Hemoglobin Glycosylated hemoglobin A Goals Healthcare Systems Hexoses Hispanic Hospitals Hyperglycemia Impairment Infant Insulin Insulin Resistance Integrated Health Care Systems Intervention Laboratories Link Lipids Measures Medical Metabolic Methodology Minority Mothers Natural History Non-Insulin-Dependent Diabetes Mellitus OGTT Pathway interactions Patient Self-Report Persons Phenotype Plasma Population Positioning Attribute Postpartum Period Prediabetes syndrome Predictive Value Pregnancy Pregnancy Complications Prospective cohort Race Recommendation Research Risk Risk Factors Sampling Testing Time Visit Woman biobank clinical care clinical risk cohort diabetes risk ethnic diversity fasting glucose feeding follow-up glucose tolerance high risk high risk population impaired glucose tolerance improved insight insulin secretion member metabolic phenotype metabolic profile metabolomics multi-racial new therapeutic target novel strategies personalized intervention point of care precision medicine predictive marker predictive modeling predictive tools prevent prospective racial diversity racial population receptor reproductive response risk prediction risk stratification tool uptake young woman

项目摘要

PROJECT SUMMARY/ABSTRACT Metabolomics has emerged as a novel approach to identify alterations in metabolites to improve prediction of type 2 diabetes mellitus (DM) beyond blood glucose. Women with gestational diabetes mellitus (GDM) have an extremely high rate of conversion to diabetes within 5 to 10 years post-delivery. However, models for prediction of DM using clinical or metabolic measures are unavailable for this high-risk group. Oral glucose tolerance testing (OGTT) is recommended at 4 to 12 weeks postpartum, but the OGTT is burdensome for new mothers and uptake is low. The Study of Women Infant Feeding, and Type 2 Diabetes After GDM (SWIFT) R01HD050625 (Gunderson PI) enrolled 1,035 women with GDM in 2008 to 2011 and administered 2-hr 75 g research OGTTs and comprehensive assessments from 6-9 weeks postpartum (baseline) and annually through two years post-delivery. This prospective, well-characterized GDM cohort is uniquely positioned to address major gaps in our understanding of the pathophysiology and timing of transitions to DM following GDM pregnancy. Our research team conducted the first study to use a targeted metabolomics approach to identify and validate a metabolite profile predictive of DM among women with GDM. This study measured 182 metabolites previously linked with incident DM in adults to identify a metabolite profile consisting of 4 analyte isotypes [BCAAs, hexoses, PCaeC40:5, SM(OH)C14:1] with predictive ability (83%) that exceeded fasting glucose alone or 2-hr post-load glucose (72-73%). Although promising, we propose to refine this profile in the entire cohort, greatly expand the lipid metabolites and test its predictive ability with longer-term follow up. The overall study goal is to identify a metabolite profile from early postpartum plasma samples that is highly predictive of incident DM up to 8 years post-delivery in women with GDM. The SWIFT cohort is exceptional for its racial/ethnic diversity (75% minority), large size, longitudinal Biobank from multiple research OGTTs and detailed assessments from early through 2 years postpartum with high retention (83%), and ongoing surveillance via electronic health records (EHR) within a stable membership (84% remain members 5 years later). The timing is optimal for a 4th in-person research visit at ~8th year post- baseline to re-assess glucose tolerance and develop prediction tools. The specific aims are: Aim 1. To identify and refine metabolite profiles at 6-9 weeks postpartum (baseline) that better predict incident diabetes following GDM pregnancy; we hypothesize that metabolite profiles identified at 6-9 weeks postpartum will be highly predictive of DM during early (2-year) and later (8-year) follow up periods; Aim 2. To characterize the metabolic profiles at consecutive time points across follow up (baseline, 1 to 2 years, and 8 years) and evaluate their relationship to transitions in glucose tolerance; we hypothesize that distinct metabolite profiles will be strongly related to the stability or deterioration in glucose tolerance over time. An exploratory aim is to develop distinct metabolite profiles highly predictive of incident DM within specific race/ethnicity groups.

项目概要/摘要代谢组学已成为一种识别代谢物变化以改进预测的新方法血糖以外的 2 型糖尿病 (DM)。患有妊娠期糖尿病（GDM）的女性有产后 5 至 10 年内转化为糖尿病的比率极高。然而，模型对于这一高危人群，无法使用临床或代谢指标来预测 DM。口服葡萄糖建议在产后 4 至 12 周进行耐受性测试 (OGTT)，但 OGTT 对新生儿来说是一个负担母亲们的吸收率很低。 GDM 后女性婴儿喂养和 2 型糖尿病的研究 (SWIFT) R01HD050625（Gunderson PI）在 2008 年至 2011 年期间招募了 1,035 名 GDM 女性，并进行了 2 小时的治疗产后 6-9 周（基线）和 75 克研究 OGTT 和综合评估交付后两年内每年一次。这个前瞻性、特征明确的 GDM 队列是独一无二的旨在解决我们对 DM 病理生理学和转变时间的理解上的主要差距 GDM 妊娠后。我们的研究团队进行了第一项使用靶向代谢组学的研究方法来识别和验证 GDM 女性中预测 DM 的代谢物谱。这项研究测量了 182 种以前与成人糖尿病相关的代谢物，以确定代谢物谱，包括 4 种分析物同种型 [BCAA、己糖、PCaeC40:5、SM(OH)C14:1] 的预测能力 (83%) 超过单独空腹血糖或负荷后 2 小时血糖 (72-73%)。尽管前景光明，但我们建议完善此配置文件在整个队列中，大大扩展脂质代谢物并通过长期随访测试其预测能力。总体研究目标是从产后早期血浆样本中确定代谢物谱，对于患有 GDM 的女性来说，它可以高度预测产后 8 年内发生的 DM。 SWIFT 队列是因其种族/族裔多样性（75% 为少数族裔）、规模庞大、来自多个国家的纵向生物库而闻名研究 OGTT 和从产后早期到产后 2 年的详细评估，保留率高 (83%)，并在稳定的会员范围内通过电子健康记录 (EHR) 进行持续监测 (84% 5 年后仍然是会员）。最佳时机是在术后第 8 年进行第四次亲自研究访问。重新评估葡萄糖耐量并开发预测工具的基线。具体目标是：目标 1. 确定并完善产后 6-9 周（基线）的代谢特征，以更好地预测糖尿病发生情况 GDM 妊娠后；我们假设产后 6-9 周确定的代谢物谱将在早期（2 年）和后期（8 年）随访期间高度预测 DM；目标 2. 表征随访期间连续时间点的代谢概况（基线、1 至 2 年和 8 年）以及评估它们与葡萄糖耐量转变的关系；我们假设不同的代谢物谱与葡萄糖耐量随时间的稳定性或恶化密切相关。一个探索性的目标是开发独特的代谢物谱，高度预测特定种族/族裔群体内的糖尿病发生率。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Underlying dyslipidemia postpartum in women with a recent GDM pregnancy who develop type 2 diabetes.

近期 GDM 妊娠且患有 2 型糖尿病的女性存在潜在的产后血脂异常。

DOI：
发表时间：
2020
期刊：
影响因子：
7.7
作者：
Lai, Mi;Al Rijjal, Dana;Röst, Hannes L;Dai, Feihan F;Gunderson, Erica P;Wheeler, Michael B
通讯作者：
Wheeler, Michael B

Prolactin and Maternal Metabolism in Women With a Recent GDM Pregnancy and Links to Future T2D: The SWIFT Study.

最近怀孕的 GDM 女性的催乳素和母体代谢以及与未来 T2D 的联系：SWIFT 研究。

DOI：
发表时间：
2022-08-18
期刊：
影响因子：
0
作者：
Zhang, Ziyi;Piro, Anthony L;Allalou, Amina;Alexeeff, Stacey E;Dai, Feihan F;Gunderson, Erica P;Wheeler, Michael B
通讯作者：
Wheeler, Michael B

Elevated Medium-Chain Acylcarnitines Are Associated With Gestational Diabetes Mellitus and Early Progression to Type 2 Diabetes and Induce Pancreatic β-Cell Dysfunction.

中链酰基肉碱升高与妊娠期糖尿病和早期进展为 2 型糖尿病有关，并诱发胰腺 β 细胞功能障碍。

DOI：
发表时间：
2018
期刊：
影响因子：
7.7
作者：
Batchuluun, Battsetseg;Al Rijjal, Dana;Prentice, Kacey J;Eversley, Judith A;Burdett, Elena;Mohan, Haneesha;Bhattacharjee, Alpana;Gunderson, Erica P;Liu, Ying;Wheeler, Michael B
通讯作者：
Wheeler, Michael B

Heterogeneity in Early Postpartum Metabolic Profiles Among Women with GDM Who Progressed to Type 2 Diabetes During 10-Year Follow-Up: The SWIFT Study.

10 年随访期间进展为 2 型糖尿病的 GDM 女性产后早期代谢特征的异质性：SWIFT 研究。

DOI：
发表时间：
2023-06-16
期刊：
影响因子：
0
作者：
Khan, Saifur R;Rost, Hannes;Cox, Brian;Razani, Babak;Alexeeff, Stacey;Wheeler, Michael B;Gunderson, Erica P
通讯作者：
Gunderson, Erica P

The discovery of novel predictive biomarkers and early-stage pathophysiology for the transition from gestational diabetes to type 2 diabetes.

发现从妊娠糖尿病到 2 型糖尿病转变的新型预测生物标志物和早期病理生理学。

DOI：
发表时间：
2019
期刊：
影响因子：
8.2
作者：
Khan, Saifur R;Mohan, Haneesha;Liu, Ying;Batchuluun, Battsetseg;Gohil, Himaben;Al Rijjal, Dana;Manialawy, Yousef;Cox, Brian J;Gunderson, Erica P;Wheeler, Michael B
通讯作者：
Wheeler, Michael B