Dornhorst A, Powell S H, Pensky J
Lancet. 1985 Jan 19;1(8421):123-6. doi: 10.1016/s0140-6736(85)91900-2.
14 hypertensive men with type II diabetes sequentially received, in random order, hydrochlorothiazide 50 mg twice a day, propranolol 80 mg twice a day, and both drugs in combination. The 3-week treatment periods were separated by a 1-week washout period. Hydrochlorothiazide significantly increased fasting glucose by 31% (p less than 0.05) and glycosylated haemoglobin (HbA1c) by 6.0% (p less than 0.10). A similar treatment period of propranolol 80 mg twice a day caused no significant increases. However, when both drugs were taken in combination, fasting glucose rose by 56% and HbA1c by 14.7% (p less than 0.01). The hyperglycaemic effect of hydrochlorothiazide and its potentiation by propranolol were independent of serum potassium and of endogenous insulin secretion as measured by urine C-peptide excretion. The combination of hydrochlorothiazide and propranolol thus seems to cause serious disturbances in glycaemic control in type II diabetics by mechanisms independent of insulin secretion.
14名患有II型糖尿病的高血压男性依次随机接受以下治疗：每天两次服用50毫克氢氯噻嗪、每天两次服用80毫克普萘洛尔，以及两种药物联合服用。为期3周的治疗阶段之间间隔1周的洗脱期。氢氯噻嗪使空腹血糖显著升高31%（p<0.05），糖化血红蛋白（HbA1c）升高6.0%（p<0.10）。每天两次服用80毫克普萘洛尔的类似治疗阶段未导致显著升高。然而，当两种药物联合服用时，空腹血糖升高了56%，HbA1c升高了14.7%（p<0.01）。氢氯噻嗪的高血糖作用及其被普萘洛尔增强的作用与血清钾以及通过尿C肽排泄测量的内源性胰岛素分泌无关。因此，氢氯噻嗪和普萘洛尔的联合使用似乎通过独立于胰岛素分泌的机制，在II型糖尿病患者中引起血糖控制的严重紊乱。
