Gerich John E
Department of Medicine, Physiology, and Pharmacology, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA.
Am J Med. 2002 Sep;113(4):308-16. doi: 10.1016/s0002-9343(02)01176-2.
Management of type 1 and type 2 diabetes mellitus with intensive insulin therapy usually includes an intermediate- or long-acting basal component for between-meal and nocturnal glycemic control, together with preprandial bolus injections of a short-acting insulin for control of meal-stimulated increases in serum glucose levels. Although the ideal basal/bolus insulin combination has yet to be found, recent developments may provide safer and more effective options. Two new short-acting semisynthetic analogs--insulin lispro and insulin aspart--can be administered as preprandial bolus injections closer to mealtime than regular human insulin, thereby synchronizing insulin administration and food absorption. In clinical trials, postprandial increases in blood glucose levels were significantly less after treatment with insulin lispro or insulin aspart than with premeal regular insulin. Because of their short duration of action, a slightly greater basal insulin supply may be needed when insulin lispro or insulin aspart is used. Inhalation devices for aerosolized regular human insulin offer another alternative to premeal subcutaneous bolus injections. Inhaled insulin is absorbed more rapidly than subcutaneous regular insulin and may therefore be given closer to mealtime. For basal therapy, insulin glargine, a new long-acting analog, is absorbed more slowly after subcutaneous administration than are conventional neutral protamine Hagedorn (NPH) and ultralente insulin, and has a relatively flat metabolic effect. Clinical trials indicate that insulin glargine is at least as effective as NPH insulin and ultralente insulin, and is associated with a reduced risk of nocturnal hypoglycemia. Other long-acting analogs, such as fatty acid acylated insulins, have been tested in animal models and are being evaluated in clinical studies.
强化胰岛素治疗1型和2型糖尿病的管理通常包括使用中效或长效基础胰岛素成分来控制餐间和夜间血糖，同时在餐前推注短效胰岛素以控制进食刺激引起的血糖水平升高。尽管尚未找到理想的基础/餐时胰岛素组合，但最近的进展可能会提供更安全、更有效的选择。两种新型短效半合成类似物——赖脯胰岛素和门冬胰岛素——可在更接近进餐时进行餐前推注，从而使胰岛素给药与食物吸收同步。在临床试验中，使用赖脯胰岛素或门冬胰岛素治疗后餐后血糖水平的升高明显低于餐前使用常规人胰岛素。由于它们作用时间短，使用赖脯胰岛素或门冬胰岛素时可能需要稍微增加基础胰岛素的供应量。雾化吸入常规人胰岛素的吸入装置为餐前皮下推注提供了另一种选择。吸入胰岛素比皮下注射常规胰岛素吸收更快，因此可以在更接近进餐时给药。对于基础治疗，新型长效类似物甘精胰岛素皮下给药后比传统的中性鱼精蛋白锌胰岛素（NPH）和特慢胰岛素吸收更慢，并且具有相对平稳的代谢作用。临床试验表明，甘精胰岛素至少与NPH胰岛素和特慢胰岛素一样有效，并且夜间低血糖风险降低。其他长效类似物，如脂肪酸酰化胰岛素，已在动物模型中进行了测试，并正在进行临床研究评估。
