Gestational Diabetes and Preeclampsia Cytokine Profiles

妊娠糖尿病和先兆子痫细胞因子谱

• 批准号: 7068607
• 负责人: RAVI THADHANI
• 金额: $ 24.73万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7068607
• 关键词: angiogenesis inhibitors; bioinformatics; biomarker; blood chemistry; clinical research; cytokine; disease /disorder proneness /risk; female; fibroblast growth factor; gestational diabetes mellitus; high throughput technology; human pregnant subject; human subject; interleukin 1; interleukin 6; interleukin 8; microarray technology; monocyte chemoattractant protein 1; placental hormones; postpartum; preeclampsia; tumor necrosis factor alpha; urinalysis

DESCRIPTION (provided by applicant): Gestational diabetes mellitus (GDM) and preeclampsia (PE) are associated with significant morbidity and mortality during pregnancy and risk for diabetes and cardiovascular disease after pregnancy. Biological mechanisms suggest alterations in specific cytokines (cytokines and growth factors) linked to inflammation, insulin resistance, and angiogenesis lead to GDM and PE. These cytokines may also serve as early markers or disease during pregnancy, and if present postpartum, critical markers for future disease. Currently, no single biochemical measure reliably identifies women at risk for these complex disorders during pregnancy, and those at risk for future disease. Likely, alterations in a specific combination of cytokines ('cytokine signatures') characterize GDM and PE. Limitations in technology and lack of prospective studies have prevented efficient and accurate quantification of cytokine combinations. Careful application of novel, multiplexed profiling techniques to quantify biologically important cytokines in women followed prospectively during pregnancy overcomes these limitations. We will test 3 hypotheses (in serum and urine): 1) Cytokine (TNF-alpha, IL-1beta, IL-6, MCP-1, IL-8) alterations identified early in pregnancy distinguish women who develop GDM or PE, and after pregnancy, characterize these same women; 2) Angiogenesis-related placental growth factors (PIGF, FGF-2) and an inhibitor (sFlt-1) are altered early in pregnancy among women who develop GDM and PE; 3) Disease-specific microarrays quantifying a set of pre-specified highly informative (aims 1, 2) cytokines can be developed, and this prospectively identifies incident GDM and PE. Our ongoing prospective pregnancy cohort permits excellent power and efficiency to test each aim. A multidisciplinary team with expertise in the epidemiology of diabetes and hypertension in pregnancy, placental biology, microarray technology, and bioinformatics will perform an innovative and cost-efficient study to understand the biology of GDM and PE, identify early markers for the conditions and suggest potential for interventions.

描述（由申请人提供）：妊娠糖尿病（GDM）和先兆子痫（PE）与怀孕期间的发病率和死亡率显着，糖尿病和怀孕后心血管疾病的风险有关。生物学机制表明，与炎症，胰岛素抵抗和血管生成有关的特定细胞因子（细胞因子和生长因子）的改变会导致GDM和PE。这些细胞因子在怀孕期间也可以作为早期标记或疾病，如果是产后，则是未来疾病的关键标记。目前，没有任何一项生化措施可靠地确定怀孕期间患有这些复杂疾病的妇女，以及患有未来疾病风险的女性。可能是GDM和PE的细胞因子（“细胞因子特征”）特定组合的改变。技术的局限性和缺乏前瞻性研究阻止了细胞因子组合的有效和准确的定量。仔细应用新型的多重分析技术来量化女性对生物学上重要的细胞因子的预期在怀孕期间遵循的限制。我们将检验3个假设（在血清和尿液中）：1）细胞因子（TNF-Alpha，IL-1Beta，IL-6，IL-6，MCP-1，IL-8）在怀孕早期发现的改变GDM或PE的妇女，并在妊娠后与这些女性相同。 2）与血管生成相关的胎盘生长因子（PIGF，FGF-2）和抑制剂（SFLT-1）在妊娠早期发生了GDM和PE的孕妇的早期改变； 3）可以开发一组预先指定的高度信息（目标1，2）细胞因子的特定疾病特异性微阵列，并前瞻性地确定了事件的GDM和PE。我们正在进行的前瞻性怀孕队列允许出色的功率和效率来测试每个目标。在妊娠，胎盘生物学，微阵列技术和生物信息学的糖尿病和高血压流行病学方面具有专业知识的多学科团队，将进行创新且具有成本效益的研究，以了解GDM和PE的生物学，并确定早期标记的状况，并暗示潜在的干预措施。