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

这项提案将检验他们的假设，即巨大儿出生时， 糖尿病母亲所生婴儿与胎儿高胰岛素血症有关 它可能是内源性的，也可能是外源性转移到胎儿身上的 作为抗体结合的胰岛素。外源转移的牛肉-猪肉胰岛素 将通过使用高性能的新建立的技术进行测量 在一个独特的脐带血清库中进行高效液相色谱分离 正在进行的妊娠期糖尿病计划项目赠款。我们假定 由β细胞引起的内源性胎儿高胰岛素血症 肥大/肥大继发于过度的营养转移 母亲，会造成持久的“新陈代谢印记”。这个印记是 表现为持续的产后胰岛素高反应性 促分泌剂，如葡萄糖。-随着时间的推移，高胰岛素血症会导致 对胰岛素的“代偿性”抵抗作用，对葡萄糖更为明显 而不是脂肪代谢，并最终导致更高的患病率 肥胖症具有向心性脂肪分布的特点。这 假说将通过检查胰岛素分泌和胰岛素来检验。 通过所谓的最小模型技术获得灵敏度。此方法使用 一种计算机程序，用于分析血糖和胰岛素对 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将被用于 评估身体成分和脱脂质量。我们假设，那些 出生时由于抗体结合的胰岛素从 母亲不应该表现出持续性的代谢异常。总而言之， 研究表明，糖尿病母亲所生的孩子将与 恰如其分。年龄匹配的非糖尿病母亲所生的对照组。这些 研究可能证明内源性胎儿高胰岛素血症是否会导致 晚年可能易患肥胖症的永久性代谢变化 或其他后遗症。这些研究也可能为使用 妊娠期糖尿病患者的高纯度胰岛素以减少抗体 应答和抗体转移可能导致巨大儿的胰岛素。

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.