Effects of the Selective Serotonin Reuptake Inhibitor Fluoxetine on Counterregulatory Responses to Hypoglycemia in Individuals With Type 1 Diabetes
Effects of the Selective Serotonin Reuptake Inhibitor Fluoxetine on Counterregulatory Responses to Hypoglycemia in Individuals With Type 1 Diabetes
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DOI：
10.2337/db08-1000
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发表时间：
2008-12-01
期刊：
影响因子：
7.7
通讯作者：
Davis, Stephen N.
中科院分区：
文献类型：
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作者：
Briscoe, Vanessa J.;Ertl, Andrew C.;Davis, Stephen N.
先前的工作已经证明了这一点。长期给予5-羟色胺再摄取抑制剂（SSRI）氟西汀增强健康人对低血糖的反调节反应。然而，几乎没有关于氟西汀对I型糖尿病低血糖期间综合生理反调节反应的影响的信息。因此，本研究的具体目的是测试，假设6周使用SSRI氟西汀会增强1型糖尿病患者自主神经系统（ANS）对低血糖的反调节反应。（14名男性/4名女性，年龄19-48岁，BMI 25 3 kg/m2，A1 C 7.0 +/- 0.4%）参加了随机、双盲2小时高胰岛素血症（9 pmol . kg（-1）。min（-1））-低血糖钳夹研究，在6周的氟西汀给药（n = 8）或相同的安慰剂（n = 10）之前和之后。葡萄糖动力学由3-氚化葡萄糖测定。肌交感神经活动（MSNA）通过显微神经造影术测定。在所有钳夹研究中，低血糖（2.8 +/- 0.1 mmol/l）和胰岛素血症（646 +/- 52 pmol/l）相似。安慰剂组的ANS、神经内分泌和代谢反调节反应保持不变。然而，氟西汀管理显着（P < 0.05）增加关键ANS（肾上腺素，去甲肾上腺素，和MSNA），代谢（内源性葡萄糖的生产和脂解），和心血管（收缩压）的反调节反应，在低血糖症。6-在1型糖尿病患者中度低血糖期间，SSRI氟西汀可以增强ANS和代谢反调节机制。这些数据还表明，在临床实践中，使用氟西汀可能有助于增加低血糖期间的肾上腺素反应。糖尿病57：3315-3322，2008
OBJECTIVE-Previous work has demonstrated that. chronic administration of the serotonin reuptake inhibitor (SSRI) fluoxetine augments counterregulatory responses to hypoglycemia in healthy humans. However, virtually no information exists regarding the effects Of fluoxetine on integrated physiological counter-regulatory responses during hypoglycemia in type I diabetes. Therefore, the specific aim of this Study was to test, the hypothesis that 6-week use of the SSRI fluoxetine would amplify autonomic nervous system (ANS) counterregulatory responses to hypoglycemia in individuals with type 1 diabetes.RESEARCH DESIGN AND METHODS-Eighteen type 1 diabetic patients (14 men/4 women aged 19-48 years with BMI 25 3 kg/m(2) and A1C 7.0 +/- 0.4%) participated in randomized, double-blind 2-h hyperinsulinemic (9 pmol . kg(-1) . min(-1))-hypoglycemic clamp studies before and after 6 weeks Of fluoxetine administration (n = 8) Or identical placebo (n = 10). Glucose kinetics was determined by 3-tritiated glucose. Muscle sympathetic nerve activity (MSNA) was determined by microneurography.RESULTS-Hypoglycemia (2.8 +/- 0.1 mmol/l) and insulinemia (646 +/- 52 pmol/l) were similar during all clamp) studies. ANS, neuroendocrine, and metabolic counterregulatory responses remained unchanged in the placebo group. However, fluoxetine administration significantly (P < 0.05) increased key ANS (epinephrine, norepinephrine, and MSNA), metabolic (endogenous glucose production and lipolysis), and cardiovascular (systolic blood pressure) counterregulatory responses during hypoglycemia.CONCLUSIONS-This study has demonstrated that. 6-week administration Of the SSRI fluoxetine can amplify ANS and metabolic counterregulatory mechanisms during moderate hypoglycemia in patients with type 1 diabetes. These data also suggest, that, the use of fluoxetine may be useful in increasing epinephrine responses during hypoglycemia in clinical practice. Diabetes 57:3315-3322, 2008