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: 8469071
• 负责人: Monique Marie Hedderson
• 金额: $ 45.05万
• 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 2014-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8469071
• 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; 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; young woman

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.

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影响。患有GDM的女性更有可能分娩妊娠期大（LGA）婴儿，其中高达50%的人将发展为2型糖尿病。然而，多达一半的GDM女性没有已知的危险因素，这表明其他因素必须参与。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GDM风险的女性，这些女性可能是预防的目标，也可能进一步加深我们对GDM及其后果的病理生理学的理解。妊娠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性的时间顺序变得重要。在三个主要目标中，我们提出评估以下生物标志物是否与GDM风险增加相关：1）胰岛素抵抗（脂联素、HMW脂联素、胎球蛋白-A和LDL-C颗粒大小），2）炎症（CRP），和3）氧化应激（GGT）。我们将在次要目标中探索：4）妊娠前脂联素及其亚型水平是否与生出LGA婴儿的风险相关，以及这种相关性是否由GDM介导; 5）在GDM女性中，妊娠前胰岛素抵抗、炎症和氧化应激生物标志物的水平及其长期变化与T2 DM和胰岛素抵抗程度相关。我们提出了一个嵌套的病例对照研究，在一个多种族队列的4,084名妇女谁参加了凯撒永久北方加州（KPNC）多相健康检查（MHC）考试之间的1984年至1996年，有血清样本储存，并有随后怀孕。我们将研究235名GDM妇女和470名血糖正常的对照妇女，这些妇女在MHC检查的年份、MHC检查时的年龄和怀孕时的年龄上相匹配。迄今为止，还没有研究检查妊娠前代谢风险和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（生命早期发生的代谢改变）的风险相关。这项研究可能在预防GDM发展为T2 DM以及后代健康后遗症方面具有转化价值。

项目成果

Risk of large-for-gestational-age newborns in women with gestational diabetes by race and ethnicity and body mass index categories.

按种族和体重指数类别划分的妊娠期糖尿病女性生下大于胎龄新生儿的风险。

• DOI: 10.1097/aog.0b013e318291b15c
• 发表时间: 2013
• 期刊: Obstetrics and gynecology
• 影响因子: 7.2
• 作者: Sridhar,SnehaB;Ferrara,Assiamira;Ehrlich,SamanthaF;Brown,SusanD;Hedderson,MoniqueM
• 通讯作者: Hedderson,MoniqueM

Pregravid liver enzyme levels and risk of gestational diabetes mellitus during a subsequent pregnancy.

• DOI: 10.2337/dc13-2229
• 发表时间: 2014-07
• 期刊: Diabetes care
• 影响因子: 16.2
• 作者: Sridhar SB;Xu F;Darbinian J;Quesenberry CP;Ferrara A;Hedderson MM
• 通讯作者: Hedderson MM

A Pre-Pregnancy Biomarker Risk Score Improves Prediction of Future Gestational Diabetes.

• DOI: 10.1210/js.2018-00200
• 发表时间: 2018-10-01
• 期刊: Journal of the Endocrine Society
• 影响因子: 4.1
• 作者: Badon SE;Zhu Y;Sridhar SB;Xu F;Lee C;Ehrlich SF;Quesenberry CP;Hedderson MM
• 通讯作者: Hedderson MM

Maternal gestational weight gain and offspring risk for childhood overweight or obesity.

• DOI: 10.1016/j.ajog.2014.02.030
• 发表时间: 2014-09
• 期刊: AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
• 影响因子: 9.8
• 作者: Sridhar, Sneha B.;Darbinian, Jeanne;Ehrlich, Samantha F.;Markman, Margot A.;Gunderson, Erica P.;Ferrara, Assiamira;Hedderson, Monique M.
• 通讯作者: Hedderson, Monique M.

Prepregnancy cardiometabolic and inflammatory risk factors and subsequent risk of hypertensive disorders of pregnancy.

• DOI: 10.1016/j.ajog.2012.05.017
• 发表时间: 2012-07
• 期刊: AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
• 影响因子: 9.8
• 作者: Hedderson, Monique M.;Darbinian, Jeanne A.;Sridhar, Sneha B.;Quesenberry, Charles P.
• 通讯作者: Quesenberry, Charles P.