PANCREATIC BETA-CELL FUNCTION & BODY COMPOSITION IN DIABETIC PREGNANCY OFFSPRING

胰腺 β 细胞功能

• 批准号: 3842625
• 负责人: MARK A SPERLING
• 金额: --
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3842625
• 关键词: body composition; electrophysiology; female; gestational diabetes mellitus; hereditary hyperglycemic obesity; high performance liquid chromatography; human birth weight; human pregnant subject; human subject; hyperinsulinism; infant human (0-1 year); insulin; insulin dependent diabetes mellitus; longitudinal human study; mother child interaction; pancreatic islet function; placental transfer; protein purification

This proposal will examine they hypotheses that macrosomia at birth, in infants born to diabetic mothers, is related to fetal hyperinsulinemia which may be of endogenous origin, or exogenously transferred to the fetus as antibody-bound insulin. The exogenously transferred beef-pork insulin will be measured via newly established techniques using high performance liquid chromatography in a unique "library" of cord sera accumulated from the ongoing Diabetes in Pregnancy Program Project Grant. We postulate that endogenous fetal hyperinsulinemia, resulting from beta cell hypertrophy/hyperplasia secondary to excessive nutrient transfer from the mother, causes a long-lasting "metabolic imprint". This imprint is manifested by persistent post-natal insulin hyper responsiveness to secretagogues such as glucose.- In time, hyperinsulinemia induces "compensatory" resistance to insulin action, more apparent for glucose than lipid metabolism, and eventually results in a higher prevalence of obesity with a characteristic centripetal fat distribution. This hypothesis will be tested by examining insulin secretion and insulin sensitivity via the so-called minimal model technique. This approach uses a computer program to analyze the glucose and insulin responses to a modified intravenous glucose tolerance test. Anthropometric measurements including skinfold thickness, and bioelectrical impedance will be used to assess body composition and fat free mass. We postulate that children who were macrosomic at birth due to antibody bound insulin transferred from the mother should not manifest persistent metabolic abnormalities. In all studies, children who were born to diabetic mothers will be compared to appropriate. age-matched controls born to non-diabetic mothers. These studies may demonstrate whether endogenous fetal hyperinsulinemia causes permanent metabolic changes in later life that may predispose to obesity or other sequelae. The studies may also provide a rationale for the use of highly purified insulins in pregnant diabetics to minimize antibody response and antibody transferred insulin that may cause macrosomia.

这项建议将审查他们的假设，巨大儿在出生时，在 糖尿病母亲所生的婴儿与胎儿高胰岛素血症有关 其可以是内源性的或外源性地转移到胎儿 作为抗体结合胰岛素。外源性牛-猪胰岛素 将通过使用高性能的新建立的技术进行测量 液相色谱法在一个独特的“图书馆”脐带血清积累， 正在进行的妊娠糖尿病项目补助金。我们推测 内源性胎儿高胰岛素血症，由β细胞引起 肥大/增生继发于过度的营养转移， 母亲，造成长期的“代谢印记”。这个印记是 表现为出生后持续的胰岛素高反应性， 促分泌素，如葡萄糖。随着时间的推移，高胰岛素血症 对胰岛素作用的“代偿性”抵抗，对葡萄糖的抵抗更明显 比脂质代谢，并最终导致更高的患病率， 具有典型的向心性脂肪分布的肥胖症。这 将通过检查胰岛素分泌和胰岛素分泌来检验假设。 通过所谓的最小模型技术的灵敏度。这种方法使用 一个计算机程序，用于分析葡萄糖和胰岛素对一种药物的反应， 改良静脉葡萄糖耐量试验人体测量 包括皮褶厚度和生物电阻抗， 评估身体成分和无脂肪质量。我们假设， 由于抗体结合的胰岛素从 母亲不应该表现出持续的代谢异常。在所有 研究中，糖尿病母亲所生的孩子将与 适当非糖尿病母亲所生的年龄匹配的对照组。这些 研究可以证明内源性胎儿高胰岛素血症是否会导致 在以后的生活中可能导致肥胖的永久性代谢变化 或其他后遗症。这些研究还可能为使用 妊娠糖尿病患者使用高纯度胰岛素，以减少抗体 反应和抗体转移胰岛素，可能导致巨大儿。