Pregravid biomarkers of GDM risk, fetal growth and progression to diabetes

GDM 风险、胎儿生长和糖尿病进展的孕前生物标志物

• 批准号: 7948659
• 负责人: Monique Marie Hedderson
• 金额: $ 54.44万
• 依托单位: KAISER FOUNDATION RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7948659
• 关键词: Adult; Age; Alcohol consumption; Behavioral; Biological Markers; Birth; Birth trauma; Body Weight Changes; C-reactive protein; California; Child; Conceptions; Data; Databases; Development; Diabetes Mellitus; Diabetes prevention; Diagnosis; Diet; Disease; Early treatment; Enzymes; Ethnic Origin; Etiology; Family history of; Fetal Growth; Flowcharts; Freezing; Functional disorder; Gamma-glutamyl transferase; Gestational Age; Gestational Diabetes; Glucose Intolerance; Growth; Health; High birth weight infant; Hormonal Change; Incidence; Infant; Inflammation; Insulin Resistance; Knowledge; Life; Liver; Low-Density Lipoproteins; Maternal Age; Measures; Mediating; Medical History; Metabolic; Metabolic Pathway; Mothers; Nested Case-Control Study; Non-Insulin-Dependent Diabetes Mellitus; OGTT; Obesity; Outcome; Oxidative Stress; Particle Size; Patient currently pregnant; Perinatal; Phenotype; Physical activity; Physiological; Play; Pregnancy; Prevention; Prevention strategy; Protein Isoforms; Race; Research; Risk; Risk Factors; Role; Sampling; Serum; Smoke; Smoking; Time; United States; Visit; Weight Gain; White Blood Cell Count procedure; Woman; adiponectin; alpha-Fetoproteins; checkup examination; cohort; follow-up; glucose tolerance; high risk; indexing; inflammatory marker; insight; interest; modifiable risk; obesity in children; offspring; parity; prevent; public health relevance

DESCRIPTION (provided by applicant): Gestational diabetes mellitus (GDM) has short and long-term consequences for both the mother and her offspring. Women with GDM are more likely to deliver a large for gestational (LGA) infant and up to 50% of them will develop type 2 diabetes. However, up to half of women with GDM have no known risk factors, suggesting that other factors must be involved. Biomarkers associated with various metabolic pathways (insulin resistance, inflammation and oxidative stress) might be useful for identifying women at risk of GDM who could be targeted for prevention and may also further our understanding of the pathophysiology of GDM and its consequences. The metabolic and hormonal changes intrinsic to pregnancy make it important to assess these metabolic biomarkers before pregnancy to determine the temporal sequence of the associations. In three primary aims we propose to evaluate whether biomarkers of: 1) insulin resistance (adiponectin, HMW adiponectin, Fetuin-A and LDL-C particle size), 2) inflammation (CRP), and 3) oxidative stress (GGT) assessed before pregnancy, are associated with increased risk GDM. We will explore in the secondary aims whether: 4) pregravid levels of adiponectin and its isoforms are associated with the risk of having a LGA infant and whether this association is mediated by GDM; 5) among the women with GDM, pre-gravid levels of biomarkers of insulin resistance, inflammation, and oxidative stress and their long-term changes are associated with T2DM and degree of insulin resistance. We propose a nested case-control study within a multi-ethnic cohort of 4,084 women who took part in the Kaiser Permanente Northern California (KPNC) multiphasic health checkup (MHC) exam between 1984-1996, had serum samples stored, and had a subsequent pregnancy. We will study 235 women with GDM and 470 normoglycemic control women matched on year of MHC exam, age at MHC exam and age at pregnancy. No studies to date have examined biomarkers of metabolic risk before pregnancy and risk of GDM. This study will fill a gap in scientific knowledge by determining if pregravid biomarkers, measured among healthy young women, are associated with the risk of GDM, a metabolic alteration occurring early in life. This research could have translational value in the prevention of GDM its progression to T2DM, and health sequelae in their offspring. PUBLIC HEALTH RELEVANCE: The incidence of GDM is increasing in the United States, however much remains unknown about its underlying cause. This study will determine for the first time if the proposed pregravid biomarkers measured among healthy young women are associated with the risk of GDM, excessive fetal growth (LGA) and progression to type 2 diabetes. Identification of pregravid metabolic biomarkers of GDM and its adverse health consequences may give insights to the underlying causes leading to the development of GDM and its consequences. This information can be used to inform strategies for GDM and diabetes prevention.

描述（由申请人提供）：妊娠期糖尿病（GDM）对母亲及其后代都有短期和长期的影响。患有GDM的女性更有可能产下大胎儿（LGA），其中高达50%的人会患上2型糖尿病。然而，多达一半的GDM女性没有已知的危险因素，这表明一定有其他因素参与其中。与各种代谢途径（胰岛素抵抗、炎症和氧化应激）相关的生物标志物可能有助于识别有GDM风险的女性，这些女性可能是预防GDM的目标，也可能进一步加深我们对GDM病理生理学及其后果的理解。妊娠期固有的代谢和激素变化使得在妊娠前评估这些代谢生物标志物以确定相关的时间序列变得非常重要。在三个主要目的中，我们建议评估以下生物标志物：1)胰岛素抵抗（脂联素，HMW脂联素，Fetuin-A和LDL-C颗粒大小），2)炎症（CRP）和3)氧化应激（GGT）在妊娠前评估是否与GDM风险增加相关。我们将在次要目的中探讨：4)妊娠前脂联素水平及其同型型是否与LGA婴儿的风险相关，以及这种关联是否由GDM介导；5) GDM女性妊娠前胰岛素抵抗、炎症和氧化应激生物标志物水平及其长期变化与T2DM和胰岛素抵抗程度相关。我们提出了一项巢式病例对照研究，在1984-1996年期间参加Kaiser Permanente Northern California （KPNC）多相健康检查（MHC）检查的4,084名多民族妇女中进行了多种族队列研究，这些妇女保存了血清样本，并随后怀孕。我们将研究235名GDM女性和470名血糖控制正常的女性，MHC检查的年份、MHC检查的年龄和怀孕年龄相匹配。到目前为止，还没有研究检测妊娠前代谢风险和GDM风险的生物标志物。这项研究将填补科学知识的空白，确定在健康年轻女性中测量的妊娠前生物标志物是否与GDM（一种发生在生命早期的代谢改变）的风险相关。这项研究可能在预防GDM发展为T2DM及其后代的健康后遗症方面具有转化价值。