Insulin Resistance and Glucose and Lipid Metabolism in Pregnancy

妊娠期胰岛素抵抗与葡萄糖和脂质代谢

• 批准号: 7616241
• 负责人: Patrick Catalano
• 金额: $ 31.8万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-06-02 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7616241
• 关键词: Adipocytes; Adipose tissue; Adolescent; Adult; Affect; Attention; Biopsy; Cell Culture Techniques; Cyclic AMP; Data; Developed Countries; Developing Countries; Development; Epidemic; Euglycemic Clamping; Fatty acid glycerol esters; Fetal Growth; Fetal Macrosomia; Fetus; Gene Expression; Gestational Diabetes; Glucose; Glucose Clamp; Goals; Growth; Height; In Vitro; Insulin; Insulin Resistance; Lipids; Lipolysis; Longitudinal Studies; Measures; Metabolic; Metabolic syndrome; Metabolism; Methodology; Modeling; Neonatal; Newborn Infant; Non-Insulin-Dependent Diabetes Mellitus; Nutrient; Obesity; Oligonucleotide Microarrays; Outcome; Overweight; Patient currently pregnant; Physiological; Placenta; Population; Pregnancy; Prevalence; Production; Proteins; Recording of previous events; Relative (related person); Research; Research Design; Research Personnel; Risk; Risk Factors; Role; Site; Testing; Ultrasonography; Weight; Woman; adipokines; base; blood glucose regulation; cytokine; fetal; glucose tolerance; in vivo; insulin sensitivity; intravenous glucose tolerance test; lipid metabolism; prevent; programs; prospective; research study; response; subcutaneous

DESCRIPTION (provided by applicant): The long term objectives of this project are to characterize and understand the mechanisms by which pregravid and early pregnancy maternal metabolism relate to increased fetal growth/adiposity among obese women. Obesity is becoming an epidemic not only in the developed nations of the world but also in developing countries, affecting not only adults and adolescents but possibly even newborns. This proposal has 3 specific aims. Specific aim 1 is to evaluate the affect of maternal obesity on placental growth and gene expression in vivo and in vitro. We hypothesize that obese women because of decreased insulin sensitivity have an increased insulin response which results in increased placental growth possibly through modulation of adipokine and lipid gene expression. Specific aim 2 is to evaluate the longitudinal changes in maternal white adipose tissue (WAT) lipid metabolism from pregravid to early pregnancy in lean women. We hypothesize that in early pregnancy there is decreased lipolysis, increased insulin suppression of lipolysis of WAT resulting in increased accretion of maternal fat mass. Consequently, the increase in WAT results in increased modulation of adipokines resulting in decreased insulin sensitivity. Specific aim 3 is to evaluate the longitudinal changes in maternal WAT lipid metabolism from pregravid to early pregnancy in obese women. We hypothesize that because obese women have decreased insulin sensitivity relative to lean women, they have increased basal lipolysis, decreased suppression of lipolysis both pregravid and in pregnancy resulting in increased lipid availability for transfer to the fetus. Because there is no accretion or loss of maternal WAT, there is no change or decrease in expression of adipokines resulting in either no change or increase in insulin sensitivity relative to pregravid measures. By performing the detailed physiologic studies in vivo combined with the in vitro experiments in a prospective longitudinal study design, we will be able to test our hypotheses in a definitive manner. We will identify mechanisms for the observed physiologic changes and neonatal outcome of fetal obesity, defined as an increase in adipose tissue based on our population normative data. If our hypotheses are correct, these studies will then provide us with a rational basis for interventional studies to possibly prevent fetal obesity which we believe is a significant risk factor the increased prevalence of the metabolic syndrome in the population.

描述（由申请人提供）：本项目的长期目标是描述和了解妊娠前和妊娠早期母体代谢与肥胖妇女胎儿生长/肥胖增加相关的机制。肥胖症不仅在世界发达国家而且在发展中国家正在成为一种流行病，不仅影响成年人和青少年，甚至可能影响新生儿。该提案有三个具体目标。具体目标1是评估母体肥胖对胎盘生长和基因表达的影响。我们假设肥胖妇女由于胰岛素敏感性降低而增加胰岛素反应，这可能通过调节脂肪因子和脂质基因表达而导致胎盘生长增加。具体目标2是评估从妊娠前到妊娠早期瘦型女性母体白色脂肪组织（WAT）脂质代谢的纵向变化。我们推测，在妊娠早期，脂肪分解减少，WAT脂肪分解的胰岛素抑制增加，导致母体脂肪量增加。因此，WAT的增加导致脂肪因子的调节增加，从而导致胰岛素敏感性降低。具体目标3是评估肥胖妇女从孕前到孕早期母亲WAT脂代谢的纵向变化。我们假设，因为肥胖妇女相对于瘦妇女胰岛素敏感性降低，他们增加了基础脂解，降低了对脂解的抑制，导致妊娠前和妊娠期脂质转移到胎儿的可用性增加。因为母体WAT没有增加或减少，所以脂肪因子的表达没有变化或减少，导致胰岛素敏感性相对于妊娠前测量值没有变化或增加。通过在体内进行详细的生理学研究，结合前瞻性纵向研究设计中的体外实验，我们将能够以明确的方式检验我们的假设。我们将确定观察到的胎儿肥胖的生理变化和新生儿结局的机制，定义为基于我们的人群标准数据的脂肪组织增加。如果我们的假设是正确的，这些研究将为干预研究提供合理的基础，以可能预防胎儿肥胖，我们认为这是人群中代谢综合征患病率增加的一个重要危险因素。