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.

项目总结/文摘

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

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

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