HYPOGLYCEMIA--MATERNAL AND PERINATAL MORTALITY

针对糖尿病和妊娠的主要临床试验集中在 高血糖对母亲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 肾上腺素能激素（肾上腺素）的反调节反应 低血糖症（HYPO）在怀孕的胰岛素依赖型糖尿病在2 血糖控制水平（见临床试验），并检查长期 肾上腺素能适应强化胰岛素治疗（IIT）。以下 将检验以下假设：1）肾上腺素能反调节功能受损 对HYPO的反应增加了HYPO的频率和严重程度， 妊娠; 2）胰岛素依赖型妊娠期间频繁HYPO 糖尿病增加孕产妇和新生儿发病率; 3）IIT导致更多 肾上腺素能受损患者中频繁和严重的HYPO 与不太严格的控制相比，反监管机制; 4.） 妊娠前前瞻性临床和生化评价将 在IIT期间确定有重度HYPO风险的患者;和5）ITT期间 妊娠导致肾上腺素能激素对HYPO的适应， 减少肾上腺素对HYPO的反应，并增加 妊娠期胰岛素依赖型糖尿病患者的重度高血压。将有四组患者 包括临床试验中的I-IV组。入组患者 PPG孕前计划将接受床边自主神经测试， 神经病变胰岛素输注研究还将进行测量， 胰高血糖素、儿茶酚胺、皮质醇和生长激素对HYPO的反应。 然后，在给药前使用胰岛素钳夹技术对患者进行研究。 怀孕，以及妊娠28周和34周。孕前激素 将这些值与妊娠期间的值进行比较，以评估肾上腺素能 适应IIT。在整个研究中，患者将使用记忆葡萄糖 反射仪，并保持与HYPO相关的事件日记，以评估 由于IIT而发生的病态母体事件，并提供 肾上腺素能适应IIT的临床测量。预计各国 肾上腺素能反调节反应缺陷患者，确定 前瞻性地，将有更频繁和更严重的HYPO发作 肾上腺素能反应完整的人更容易接受， 可以设计适当的治疗方案以避免频繁的HYPO， 这些病人。钳夹研究显示， 妊娠期和持续时间等既往反应完整的患者 IIT的进展。

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.