Kihara Y, Ogami Y, Tabaru A, Unoki H, Otsuki M
Third Department of Internal Medicine, University of Occupational and Environmental Health, School of Medicine, Kitakyushu 807, Japan.
J Gastroenterol. 1997 Dec;32(6):777-82. doi: 10.1007/BF02936954.
Glucose intolerance and diabetes mellitus are both prevalent in patients with chronic liver diseases. We examined the efficacy and systemic safety of therapy with an alpha-glucosidase inhibitor, acarbose, in diabetes mellitus associated with chronic liver diseases. Twenty patients with chronic hepatitis or liver cirrhosis and overt diabetes mellitus received acarbose (taken orally) for 8 weeks. The initial dosage of acarbose was 50 mg three times daily, taken before meals; this was increased to 100 mg three times daily after 2 weeks. The mean fasting plasma glucose level was 173.7 +/- 18.6 mg/dl (mean +/- SE) at entry, and was significantly decreased to 132.9 +/- 7.5 mg/dl (P < 0.05) after 8 weeks of acarbose treatment. The improved glycemic control was reflected by a significant decrease in glycosylated hemoglobin (HbA1c) from 7.2 +/- 0.3% at entry to 6.3 +/- 0.2% (P < 0.05) after 8 weeks. Serum levels of both aspartate and alanine aminotransferases fluctuated during acarbose treatment, probably due to the natural course of chronic liver diseases, but the mean values had decreased after 8 weeks of treatment. Plasma ammonia levels increased, from 61.3 +/- 10.7 micrograms/dl to 71.1 +/- 9.6 micrograms/dl after 8 weeks of acarbose treatment but the increase was not significant. Clinically significant elevation of plasma ammonia concentration was seen in 2 cirrhotic patients (121 and 124 micrograms/dl); this was asymptomatic and gradually returned to the normal range despite continuous acarbose treatment in one patient, and was reversed after the withdrawal of acarbose with the concomitant administration of lactulose in the other patient. No other blood tests results, including albumin, cholinesterase, and prothrombin time, or lipid profile and nutritional status, in terms of rapid turnover proteins, prealbumin, retinol binding protein, and transferin, were altered throughout the study period. These results indicate that diabetes mellitus associated with chronic liver diseases may be safely and effectively treated with acarbose. However, clinicians must be aware of the possibility of hyperammonemia when they prescribe acarbose for patients with diabetes mellitus and advanced liver cirrhosis.
葡萄糖耐量异常和糖尿病在慢性肝病患者中均很常见。我们研究了α-葡萄糖苷酶抑制剂阿卡波糖治疗慢性肝病相关糖尿病的疗效和全身安全性。20例慢性肝炎或肝硬化合并显性糖尿病患者接受阿卡波糖(口服)治疗8周。阿卡波糖初始剂量为每日3次,每次50mg,于餐前服用;2周后增至每日3次,每次100mg。治疗开始时平均空腹血糖水平为173.7±18.6mg/dl(平均值±标准误),阿卡波糖治疗8周后显著降至132.9±7.5mg/dl(P<0.05)。糖化血红蛋白(HbA1c)从治疗开始时的7.2±0.3%显著降至8周后的6.3±0.2%(P<0.05),这反映了血糖控制得到改善。在阿卡波糖治疗期间,天冬氨酸转氨酶和丙氨酸转氨酶的血清水平均有波动,这可能是由于慢性肝病的自然病程所致,但治疗8周后平均值有所下降。血浆氨水平升高,阿卡波糖治疗8周后从61.3±10.7μg/dl升至71.1±9.6μg/dl,但升高不显著。2例肝硬化患者血浆氨浓度出现临床显著升高(分别为121和124μg/dl);其中1例患者无症状,尽管继续服用阿卡波糖,但血浆氨浓度逐渐恢复正常范围,另1例患者在停用阿卡波糖并同时服用乳果糖后血浆氨浓度恢复正常。在整个研究期间,包括白蛋白、胆碱酯酶、凝血酶原时间,以及快速周转蛋白、前白蛋白、视黄醇结合蛋白和转铁蛋白方面的血脂谱和营养状况等其他血液检测结果均未改变。这些结果表明,阿卡波糖可安全有效地治疗慢性肝病相关糖尿病。然而,临床医生在为糖尿病合并晚期肝硬化患者开具阿卡波糖处方时,必须意识到高氨血症的可能性。