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

• 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
• 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

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.

项目摘要/摘要 代谢组学已成为一种新的方法，可以鉴定代谢产物的变化以改善预测 超出血糖的2型糖尿病（DM）。妊娠糖尿病（GDM）的妇女患有 交付后5到10年内，转化为糖尿病的率极高。但是，模型 对于这一高风险组，使用临床或代谢措施对DM的预测是不可用的。口服葡萄糖 建议在产后4至12周时进行耐受性测试（OGTT），但OGTT对于新的很繁重 母亲和吸收很低。 GDM（SWIFT）后的女性婴儿喂养的女性喂养和2型糖尿病的研究 R01HD050625（Gunderson PI）在2008年至2011年招募了1,035名GDM的女性，并管理2小时 75 G研究和从产后6-9周（基线）和 每年两年后交付。这个预期的，良好的GDM队列是独特的 在我们对DM过渡的病理生理学和时机的理解时，可以解决重大差距 GDM怀孕后。我们的研究团队进行了第一项研究使用目标代谢组学的研究 识别和验证GDM女性DM的代谢物概况的方法。这项研究 测量的182个代谢物先前与成年人中的事件DM相关，以识别组成的代谢物剖面 超过预测能力（83％）的4种分析物同型[BCAAS，HEXOSES，PCAEC40：5，SM（OH）C14：1] 单独禁食葡萄糖或2小时后葡萄糖（72-73％）。尽管很有希望，但我们建议完善此个人资料 在整个队列中，大大扩展了脂质代谢物，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识别出代谢产物的特征 高度可预测GDM女性寄托后8年的DM事件。迅速的队列是 其种族/族裔多样性（75％的少数民族），大尺寸，纵向生物库的异常 在产后早期至2年的详细评估研究和详细评估，并具有很高的保留率 （83％），以及通过电子健康记录（EHR）进行稳定会员资格的持续监视（84％ 5年后，剩下的成员）。时间安排对于在〜8年左右的第四次面对面研究访问是最佳的 - 重新评估葡萄糖耐受性并开发预测工具的基线。具体目的是：目标1。 在产后6-9周（基线）识别和完善代谢物轮廓，以更好地预测入射糖尿病 GDM怀孕；我们假设在产后6-9周确定的代谢物谱将是 在早期（2年）和更晚（8年）的随访期间高度预测DM；目标2。 在后续行动（基线，1至2年和8年）的连续时间点的代谢概况和 评估它们与葡萄糖耐量过渡的关系；我们假设独特的代谢物谱 随着时间的流逝，葡萄糖耐量的稳定性或恶化将密切相关。探索目的是 在特定种族/族裔群体中开发高度预测事件DM的独特代谢物谱。

项目成果

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: 10.1210/clinem/dgac346
• 发表时间: 2022
• 期刊: The Journal of clinical endocrinology and metabolism
• 作者: Zhang,Ziyi;Piro,AnthonyL;Allalou,Amina;Alexeeff,StaceyE;Dai,FeihanF;Gunderson,EricaP;Wheeler,MichaelB
• 通讯作者: Wheeler,MichaelB

Diminished Sphingolipid Metabolism, a Hallmark of Future Type 2 Diabetes Pathogenesis, Is Linked to Pancreatic β Cell Dysfunction.

• DOI: 10.1016/j.isci.2020.101566
• 发表时间: 2020-10-23
• 期刊: iScience
• 影响因子: 5.8
• 作者: Khan SR;Manialawy Y;Obersterescu A;Cox BJ;Gunderson EP;Wheeler MB
• 通讯作者: Wheeler MB

Association of infant diet with subsequent obesity at 2-5 years among children exposed to gestational diabetes: the SWIFT study.

• DOI: 10.1007/s00125-020-05379-y
• 发表时间: 2021-05
• 期刊: Diabetologia
• 影响因子: 8.2
• 作者: Vandyousefi S;Davis JN;Gunderson EP
• 通讯作者: Gunderson EP

Intensive lactation among women with recent gestational diabetes significantly alters the early postpartum circulating lipid profile: the SWIFT study.

• DOI: 10.1186/s12916-021-02095-1
• 发表时间: 2021-10-08
• 期刊: BMC medicine
• 影响因子: 9.3
• 作者: Zhang Z;Lai M;Piro AL;Alexeeff SE;Allalou A;Röst HL;Dai FF;Wheeler MB;Gunderson EP
• 通讯作者: Gunderson EP