ANTIDEPRESSANT THERAPY AND HYPOGLYCEMIA

抗抑郁治疗和低血糖

• 批准号: 6954866
• 负责人: DIANNE FIGLEWICZ LATTEMANN
• 金额: $ 13.69万
• 依托单位: SEATTLE INST FOR BIOMEDICAL/CLINICAL RES
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6954866
• 关键词: antidepressants; comorbidity; depression; diabetes mellitus; drug administration routes; drug adverse effect; endocrine pharmacology; hypoglycemia; laboratory rat; neuropharmacology; serotonin inhibitor; sertraline

DESCRIPTION (provided by applicant): Findings from the Diabetes Control and Complications Trial have shown that tight glycemic control, achieved through intensive insulin therapy, prevents and reduces the onset and progression of the complications associated with uncontrolled diabetes. To achieve this, a high level of patient self-care is critical. Patients with diabetes, however, are twice as likely to develop depression compared to the general population. For diabetic patients with co-morbid depression, diligent self-care and diabetes management can be profoundly impaired, resulting in a significantly greater risk of developing diabetes-related complications and morbidity. The commonly prescribed antidepressant class of selective serotonin reuptake inhibitors (SSRIs) has been associated with significant incidence of hypoglycemia. The mechanism(s) underlying this have not been elucidated. The proposed studies will test the hypothesis that the SSRIs may impair the ability of the brain to detect hypoglycemia by reducing the responsiveness of hindbrain glucose sensing neurons that are critical to hypoglycemia detection and activation of counterregulatory responses. The following hypotheses will be tested: I) Peripheral administration of SSRIs decrease the counterregulatory response to hypoglycemia and II) SSRIs delivered directly into the terminal fields of hindbrain glucose sensing neurons impair the counterregulatory response to hypoglycemia. To test these hypotheses we will administer sertraline, acutely or chronically, to non-diabetic Wistar rats and will measure the neuroendocrine counterregulatory response to a bout of hypoglycemia. Finally, patients with diabetes exhibit a significant increase in severe hypoglycemic episodes. Thus, we will test the hypothesis III) that SSRIs are more detrimental to counterregulation in diabetic vs. non-diabetic rats. The results of these studies will provide new knowledge that ultimately may assist primary physicians in determining the most advantageous treatment for their diabetic patients with depression.

描述（由申请人提供）：糖尿病控制和并发症试验的结果表明，通过强化胰岛素治疗实现严格的血糖控制，可以预防和减少与不受控制的糖尿病相关的并发症的发生和进展。为了实现这一目标，患者的高水平自我护理至关重要。然而，糖尿病患者患抑郁症的可能性是普通人群的两倍。对于患有抑郁症的糖尿病患者来说，勤奋的自我护理和糖尿病管理可能会受到严重损害，导致发生糖尿病相关并发症和发病的风险显着增加。常用的抗抑郁药选择性血清素再摄取抑制剂 (SSRI) 与低血糖的显着发生率相关。其背后的机制尚未阐明。拟议的研究将检验以下假设：SSRI 可能通过降低后脑葡萄糖传感神经元的反应性来损害大脑检测低血糖的能力，而后脑葡萄糖传感神经元对于低血糖检测和反调节反应的激活至关重要。将测试以下假设：I) 外周施用 SSRI 会降低对低血糖的反调节反应，II) 直接递送到后脑葡萄糖传感神经元末端区域的 SSRI 会损害对低血糖的反调节反应。为了检验这些假设，我们将对非糖尿病 Wistar 大鼠急性或长期给予舍曲林，并测量对低血糖发作的神经内分泌反调节反应。最后，糖尿病患者的严重低血糖发作显着增加。因此，我们将检验假设 III)，即 SSRIs 对糖尿病大鼠的反调节作用比非糖尿病大鼠更有害。这些研究的结果将提供新的知识，最终可以帮助初级医生确定糖尿病合并抑郁症患者最有利的治疗方法。