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.
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