Lawrence A M, Abraira C
Department of Medicine, Loyola University of Chicago Stritch School of Medicine, Maywood, Illinois.
Am J Med. 1988 Nov 28;85(5A):153-8. doi: 10.1016/0002-9343(88)90409-3.
It is certainly acknowledged, albeit rather recently, that adequate control of hyperglycemia in type II diabetic patients is generally poor at best. A heightened realization of this fact and hopes that control of hyperglycemia may prevent complications or limit their severity have spawned newer approaches toward achieving improved glycemic control through changes in standard programmatic care with diet, exercise, oral agents or insulin therapy, and management of hypertension and obesity. Insulin taken at bedtime to control nocturnal hepatic glucose output, multiple doses of regular insulin coupled with frequent blood sugar measurements, and combined insulin and oral agents are approaches currently under trial in several centers. Interest in combination therapy stems in part from residual concern that hyperinsulinemia may contribute to the development of atherosclerosis, and to evidence that the sulfonylureas, especially the second-generation drugs, improve sensitivity to the glycolytic effects of insulin, thereby reducing insulin resistance. More than a dozen serious studies of combined therapy have been reported since the early 1980s. This study is unique, however, in several respects since non-obese, type II, insulin-requiring diabetic persons were chosen for study and were hospitalized prior to initiating the actual investigation in order to secure optimal diabetic control and thereby ensure greater sensitivity of the beta cell. Twenty type II diabetic patients were studied in a double-blinded, placebo-controlled trial with insulin and glyburide. All were treated with intermediate-acting insulin and adjustments were made as necessary to achieve optimal control, after which the patients were randomly assigned to either an insulin-and-glyburide program or to insulin-plus-placebo treatment. Thereafter, patients were followed in an outpatient setting for four months, after which time they were rehospitalized for final assessment. Standard chemistries, urinary glucose, glycosylated hemoglobins, and urinary C-peptide levels were measured. The fasting serum glucose level remained normal in the glyburide/insulin-treated group, whereas these were significantly higher in the placebo-plus-insulin group at four and at eight weeks. Glycosylated hemoglobin levels rose progressively in the placebo- and insulin-treated group and by 16 weeks were significantly higher than measurements from the insulin- and glyburide-treated group of patients (p less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)
尽管是相当近期才得到承认,但II型糖尿病患者高血糖的充分控制总体而言充其量也很不理想。对这一事实的进一步认识以及控制高血糖或许可以预防并发症或减轻其严重程度的希望,催生了一些新方法,旨在通过改变饮食、运动、口服药物或胰岛素治疗等标准方案护理以及高血压和肥胖症管理来实现更好的血糖控制。睡前服用胰岛素以控制夜间肝脏葡萄糖输出、多次注射常规胰岛素并频繁测量血糖,以及胰岛素与口服药物联合使用,这些方法目前正在多个中心进行试验。联合治疗的兴趣部分源于对高胰岛素血症可能导致动脉粥样硬化发展的持续担忧,以及有证据表明磺脲类药物,尤其是第二代药物,可提高对胰岛素糖酵解作用的敏感性,从而降低胰岛素抵抗。自20世纪80年代初以来,已经报道了十几项关于联合治疗的严肃研究。然而,这项研究在几个方面具有独特性,因为选择了非肥胖的II型胰岛素依赖型糖尿病患者进行研究,并在开始实际调查之前住院,以确保实现最佳的糖尿病控制,从而确保β细胞具有更高的敏感性。20名II型糖尿病患者在一项使用胰岛素和格列本脲的双盲、安慰剂对照试验中接受研究。所有患者均接受中效胰岛素治疗,并根据需要进行调整以实现最佳控制,之后患者被随机分配到胰岛素加格列本脲方案或胰岛素加安慰剂治疗组。此后,患者在门诊环境中随访四个月,之后再次住院进行最终评估。测量了标准化学指标、尿糖、糖化血红蛋白和尿C肽水平。格列本脲/胰岛素治疗组的空腹血糖水平保持正常,而安慰剂加胰岛素组在四周和八周时显著更高。安慰剂和胰岛素治疗组的糖化血红蛋白水平逐渐上升,到16周时显著高于胰岛素和格列本脲治疗组患者的测量值(p小于0.05)。(摘要截选至400字)