Lao B, Czyzyk A, Szutowski M, Szczepanik Z
Kliniki Gastroenterologii i Chorób Przemiany Materii, Warszawie.
Pol Arch Med Wewn. 1993 Jun;89(6):463-79.
The oral ethanol loading test (0.5 g per kg b.m. given as 40% solution) was carried out in 5 groups, each of 10 patients with non-insulin-dependent (type 2) diabetes before and after 10 days of treatment with one of the following sulphonylurea derivatives: tolbutamide 0.5 t.i.d., chlorpropamide 0.5 once daily morning, glibornuride 0.025 t.i.d, glibenclamide 0.005 t.i.d. and glipizide 0.005 t.i.d. The response to alcohol (facial flush, heart rate, blood pressure) were compared, and blood concentration of ethanol, acetaldehyde, pyruvate, lactate, carbonates as well as blood pH, pO2 and pCO2 were determined in fasting state and during 6 hours after alcohol ingestion. In all patients the family history of diabetes and the presence and degree of vascular complications were registered. Evident flushing phenomenon was observed in 6 patients treated with chlorpropamide, in 3 treated with tolbutamide, in 2 treated with glibenclamide, in one receiving glibornuride and in none treated with glipizide. All drugs caused a greater rise of blood ethanol and acetaldehyde levels in relation to the control tests, but the difference reached statistical significance only in the group receiving chlorpropamide. Moreover, patients (pooled) with positive thermographic response had also significantly higher blood levels of ethanol and acetaldehyde during the second test. The ratio of acetaldehyde to ethanol concentration in blood (mumol:mmol) was not significantly changed in any group indicating parallel impairment of both steps of ethanol metabolism. All studied drugs intensified to a similar degree the alcohol-induced hypoglycaemia, but had no significant effect on the decrease of blood pyruvate level neither on the increase of blood lactate level. They didn't change the post-alcohol decrease of blood bicarbonate and pH, and didn't modify the behaviour of partial gas pressure. There was also no difference between pooled groups of patients with positive and negative thermographic reaction with respect to family history of diabetes and frequency and intensity of vascular complications. It is concluded that in patients with non-insulin-dependent (type 2) diabetes the second generation sulphonylurea derivatives are associated with lower risk of alcohol intolerance in case of its incidental ingestion in small amounts. The hypothesis of association of positive thermographic reaction to alcohol during treatment with sulphonylurea derivatives with more frequent occurrence of diabetes in family members and lower tendency to vascular complications was not confirmed.
对5组患者进行口服乙醇负荷试验（按0.5 g/kg体重给予40%溶液），每组10例非胰岛素依赖型（2型）糖尿病患者，在使用下列磺脲类衍生物之一治疗10天前后进行：甲苯磺丁脲0.5 g，每日3次；氯磺丙脲0.5 g，每日清晨1次；格列波脲0.025 g，每日3次；格列本脲0.005 g，每日3次；格列吡嗪0.005 g，每日3次。比较对酒精的反应（面部潮红、心率、血压），并在空腹状态及饮酒后6小时测定血液中乙醇、乙醛、丙酮酸、乳酸、碳酸盐的浓度以及血液pH、pO₂和pCO₂。记录所有患者的糖尿病家族史以及血管并发症的存在情况和严重程度。观察到6例使用氯磺丙脲治疗的患者、3例使用甲苯磺丁脲治疗的患者、2例使用格列本脲治疗的患者、1例使用格列波脲治疗的患者出现明显的潮红现象，而使用格列吡嗪治疗的患者未出现。与对照试验相比，所有药物均使血液中乙醇和乙醛水平有更大幅度的升高，但仅在使用氯磺丙脲的组中差异具有统计学意义。此外，热成像反应呈阳性的患者（合并）在第二次试验期间血液中乙醇和乙醛水平也显著更高。血液中乙醛与乙醇浓度的比值（μmol:mmol）在任何组中均无显著变化，表明乙醇代谢的两个步骤均受到平行损害。所有研究药物在类似程度上加重了酒精诱导的低血糖，但对血液丙酮酸水平的降低和血液乳酸水平的升高均无显著影响。它们未改变饮酒后血液碳酸氢盐和pH的降低，也未改变分压的变化情况。在糖尿病家族史以及血管并发症的发生频率和严重程度方面，热成像反应呈阳性和阴性的患者合并组之间也没有差异。得出结论，对于非胰岛素依赖型（2型）糖尿病患者，第二代磺脲类衍生物在偶然少量摄入酒精的情况下与酒精不耐受风险较低相关。磺脲类衍生物治疗期间对酒精的热成像反应呈阳性与家族中糖尿病发生频率较高及血管并发症倾向较低相关的假设未得到证实。
