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

该提案将检验他们的假设，即出生时巨大儿 糖尿病母亲所生的婴儿，与胎儿高胰岛素血症有关 可能是内源性的，也可能是外源性转移给胎儿的 作为抗体结合胰岛素。外源转移牛猪胰岛素 将通过使用高性能的新建立的技术进行测量 液相色谱法在独特的脐带血清“文库”中积累 正在进行的妊娠期糖尿病计划项目拨款。我们假设 β细胞引起的内源性胎儿高胰岛素血症 肥大/增生继发于过度营养转移 母亲，会造成持久的“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，高胰岛素血症会诱发 对胰岛素作用的“代偿性”抵抗，对于葡萄糖更明显 高于脂质代谢，并最终导致更高的患病率 具有特征性向心脂肪分布的肥胖。这个 假设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的灵敏度。这种方法使用 一个计算机程序来分析葡萄糖和胰岛素对某种物质的反应 改良的静脉内葡萄糖耐量试验。人体测量 包括皮褶厚度和生物电阻抗将用于 评估身体成分和去脂质量。我们假设孩子们 由于抗体结合的胰岛素从 母亲不应表现出持续的代谢异常。总共 研究将糖尿病母亲所生的孩子与 适当的。非糖尿病母亲所生的年龄匹配的对照。这些 研究可能证明内源性胎儿高胰岛素血症是否会导致 晚年的永久性代谢变化可能导致肥胖 或其他后遗症。这些研究还可能为使用 怀孕糖尿病患者使用高度纯化的胰岛素可最大程度地减少抗体 反应和抗体转移胰岛素可能导致巨大儿。

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.