Deininger E, Oltmanns K M, Wellhoener P, Fruehwald-Schultes B, Kern W, Heuer B, Dominiak P, Born J, Fehm H L, Peters A
Medical Clinic I, Department of Clinical Neuroendocrinology, Institute for Pharmacology, Medical University Luebeck, Ratzeburger Allee 160, D-23538 Luebeck, Germany.
Clin Pharmacol Ther. 2001 Oct;70(4):362-9.
Reduced awareness of hypoglycemic symptoms and compromised hormonal counterregulation increase the risk of severe hypoglycemia in people with diabetes mellitus. Up to the present, angiotensin 1 receptor blockers, which play an important role in controlling diabetic complications, have not been known to increase the risk of hypoglycemia. Nevertheless, we observed 3 cases of diabetic patients complaining of reduced awareness of hypoglycemic symptoms while they were under treatment with losartan in our outpatients clinic. We therefore investigated the effects of losartan on symptomatic and hormonal responses to hypoglycemia in humans.
We carried out a randomized, double-blind, crossover study including 16 healthy men. The subjects received losartan 50 mg/d versus placebo. Treatment periods lasted for 7 days and were followed by a stepwise hypoglycemic clamp session (4.5 to 3.8 to 3.1 to 2.4 mmol/L) with measurement of counterregulatory hormones (epinephrine, norepinephrine, adrenocorticotropin, cortisol, glucagon), symptoms, and hemodynamic parameters (blood pressure, heart rate).
Losartan attenuated the hypoglycemia-induced rise in plasma epinephrine (6480 +/- 490 pmol/L versus placebo 8970 +/- 790 pmol/L; P <.001) and the rise in plasma adrenocorticotropin (21 +/- 2 pmol/L versus 26 +/- 3 pmol/L; P <.01). Losartan also reduced symptom scores during hypoglycemia (P <.05).
We conclude that short-term treatment with losartan slightly attenuates symptomatic and hormonal responses to hypoglycemia. At present, for patients who are unaware of hypoglycemia and who require antihypertensive or nephroprotective treatment, we would recommend caution concerning treatment with losartan.
低血糖症状意识降低以及激素对抗调节功能受损会增加糖尿病患者发生严重低血糖的风险。到目前为止，在控制糖尿病并发症方面发挥重要作用的血管紧张素1受体阻滞剂尚未被发现会增加低血糖风险。然而，我们在门诊观察到3例糖尿病患者在服用氯沙坦治疗期间出现低血糖症状意识降低的情况。因此，我们研究了氯沙坦对人体低血糖症状及激素反应的影响。
我们进行了一项随机、双盲、交叉研究，纳入16名健康男性。受试者分别接受50mg/d氯沙坦与安慰剂治疗。治疗期持续7天，随后进行逐步低血糖钳夹试验（血糖从4.5降至3.8再降至3.1最后降至2.4mmol/L），并测量对抗调节激素（肾上腺素、去甲肾上腺素、促肾上腺皮质激素、皮质醇、胰高血糖素）、症状及血流动力学参数（血压、心率）。
氯沙坦减弱了低血糖诱导的血浆肾上腺素升高（6480±490pmol/L，安慰剂组为8970±790pmol/L；P<.001）以及血浆促肾上腺皮质激素升高（21±2pmol/L，安慰剂组为26±3pmol/L；P<.01）。氯沙坦还降低了低血糖期间的症状评分（P<.05）。
我们得出结论，氯沙坦短期治疗会轻微减弱对低血糖的症状及激素反应。目前，对于未意识到低血糖且需要进行降压或肾脏保护治疗的患者，我们建议谨慎使用氯沙坦进行治疗。
