HYPOGLYCEMIA, MATERNAL AND PERINATAL MORTALITY

低血糖、孕产妇和围产儿死亡率

• 批准号: 3878440
• 负责人: MICHAEL A BERK
• 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/3878440
• 关键词: adrenergic receptor; behavior test; blood glucose; child physical development; child psychology; congenital disorders; diabetic neuropathy; disease /disorder proneness /risk; embryo /fetus monitoring; environmental adaptation; epinephrine; gestational age; gestational diabetes mellitus; glucose metabolism; hormone regulation /control mechanism; human pregnant subject; human subject; hypoglycemia; infant human (0-1 year); infant mortality; insulin; insulin dependent diabetes mellitus; longitudinal human study; newborn human (0-6 weeks); patient care planning; perinatal; pregnancy disorder; therapy compliance

Major clinical trials dealing with diabetes and pregnancy have focused on the effects of hyperglycemia on maternal morbidity and neonatal outcome. This prospective study will evaluate the consequences of impaired adrenergic hormonal (epinephrine) counterregulatory responses to hypoglycemia (HYPO) in the pregnant insulin dependent diabetic at two levels of glycemic control (See Clinical Trial) and to examine longer term adrenergic adaptation to intensive insulin therapy (IIT). The following hypotheses will be tested: 1) Impairment of adrenergic counterregulatory response to HYPO increases the frequency and severity of HYPO during pregnancy; 2) Frequent HYPO during pregnancy in the insulin dependent diabetic increases maternal and neonatal morbidity; 3) IIT results in more frequent and severe HYPO in patients with impaired adrenergic counterregulatory mechanisms compared to less strict control; 4.) Prospective clinical and biochemical evaluation pre-pregnancy will identify patients at risk for severe HYPO during IIT: and 5) ITT during pregnancy results in adaptation of adrenergic hormonal response to HYPO by diminishing the epinephrine response to HYPO and increases the risk of severe HYPO in pregnant IDDM patients. Four groups of patients will be studied comprising groups I-IV in the Clinical Trial. Patients enrolled in the PPG Pre-Pregnancy Program will undergo bedside tests for autonomic neuropathy. Insulin infusion studies will also be done with measurement of glucagon, catecholamine, cortisol and growth hormone responses to HYPO. Patients will then be studied using the insulin clamp technique prior to conception, and at 28 and 34 weeks gestation. Pre-pregnancy hormonal values will be compared to those during pregnancy to assess adrenergic adaptation to IIT. For the entire study, patients will use memory glucose reflectance meters, and keep diaries of events related to HYPO to assess morbid maternal events occurring as a result of IIT and to provide a clinical measure of adrenergic adaptation to IIT. It is anticipated that patients with defective adrenergic counter regulatory response, identified prospectively, will have more frequent and more severe episodes of HYPO than those with intact adrenergic response so that in the future an appropriate therapeutic regime can be designed to avoid frequent HYPO in these patients. Clamp studies will show diminished adrenergic response in those patients with previously intact responses as gestation and duration of the IIT progresses.

涉及糖尿病和妊娠的主要临床试验集中于 高血糖对孕产妇发病率和新生儿结局的影响。 这项前瞻性研究将评估受损的后果 肾上腺素能激素（肾上腺素）的反调节反应 怀孕两岁胰岛素依赖型糖尿病患者的低血糖 (HYPO) 血糖控制水平（参见临床试验）并进行长期检查 肾上腺素能适应强化胰岛素治疗（IIT）。下列 将检验假设：1) 肾上腺素能反调节功能受损 对 HYPO 的反应会增加 HYPO 的频率和严重程度 怀孕; 2) 胰岛素依赖者在怀孕期间频繁发生HYPO 糖尿病会增加孕产妇和新生儿的发病率； 3）个人所得税带来更多 肾上腺素能受损患者频繁且严重的 HYPO 反监管机制与不太严格的控制相比； 4.) 孕前前瞻性临床和生化评估将 识别 IIT 期间有严重 HYPO 风险的患者：以及 5) ITT 期间 妊娠导致肾上腺素能激素对 HYPO 的反应适应 减少肾上腺素对 HYPO 的反应并增加以下风险 妊娠 IDDM 患者出现严重 HYPO。四组患者将被 在临床试验中研究了 I-IV 组。患者入组 PPG 孕前计划将接受床边自主神经测试 神经病。胰岛素输注研究也将通过测量来完成 胰高血糖素、儿茶酚胺、皮质醇和生长激素对 HYPO 的反应。 然后，在治疗前将使用胰岛素钳夹技术对患者进行研究 受孕以及妊娠 28 周和 34 周时。孕前荷尔蒙 将与怀孕期间的值进行比较，以评估肾上腺素能 适应个人所得税。在整个研究中，患者将使用记忆葡萄糖 反射率计，并记录与 HYPO 相关的事件日记以进行评估 因 IIT 而发生的病态孕产妇事件，并提供 肾上腺素能适应 IIT 的临床测量。预计 已确定肾上腺素能反调节反应有缺陷的患者 未来，HYPO 的发作会更频繁、更严重 比那些具有完整肾上腺素反应的人更好，因此在未来 可以设计适当的治疗方案以避免频繁的 HYPO 这些病人。钳夹研究将显示肾上腺素能反应减弱 那些先前对妊娠和持续时间反应完好的患者 个人所得税的进展。