Bolli G B, Perriello G, Fanelli C G, De Feo P
Department of Internal Medicine and Endocrine and Metabolism and Sciences, University of Perugia, Italy.
Diabetes Care. 1993 Dec;16 Suppl 3:71-89. doi: 10.2337/diacare.16.3.71.
A major problem in replacing insulin in type I diabetes mellitus is that currently no depot preparation exists that is capable of mimicking the background insulin secretion of the healthy pancreas. Because all of the currently available intermediate- or long-acting insulin preparations have a peaked-action profile, excess insulin action at midnight and insulin waning at dawn occur whenever such an insulin preparation is given at supper time. If the target fasting plasma glucose is the ambitious near-normoglycemia of intensive insulin therapy, intermediate-acting insulin at suppertime easily results in hypoglycemia in the early evening hours and hyperglycemia in the fasting state. The problems of overnight glycemia in type I diabetes are further complicated by the dawn phenomenon and the Somogyi phenomenon. The dawn phenomenon is the combination of an initial decrease in insulin requirements between approximately 2400 and approximately 0300, followed by an increase in the insulin needs between approximately 0500 and approximately 0800. The dawn phenomenon is the result of changes in hepatic (and extrahepatic) insulin sensitivity, which are best attributed to nocturnal growth hormone secretion. The dawn phenomenon is a day-to-day reproducible event that occurs in nearly all diabetic patients. Its contribution to fasting hyperglycemia correlates with diabetes duration (inversely) and the HbA1c percentage (directly). Overall, it is estimated that the specific contribution of the dawn phenomenon to fasting hyperglycemia is approximately 2 mM (approximately 35 mg/dl), but it may be much greater because of the warning of the depot-insulin preparation injected the previous evening. The Somogyi phenomenon, strictly speaking, refers to fasting hyperglycemia that occurs after inducement of nocturnal hypoglycemia by regular insulin. Because the present therapeutic regimens of NPH/Lente insulin given at suppertime cause overnight hyperinsulinemia, excessive fasting hyperglycemia rarely follows nocturnal hypoglycemia, except when excessive glucose is ingested to correct hypoglycemia. However, nocturnal hypoglycemia may easily deteriorate glycemic control later in the day, because it induces prolonged posthypoglycemic insulin resistance, which results in postbreakfast and late-morning hyperglycemia. With nocturnal insulin therapy, it is important to consider the problems of insulin pharmacokinetics, the dawn phenomenon, and the Somogyi phenomenon to prevent both nocturnal hypoglycemia and excessive fasting hyperglycemia.(ABSTRACT TRUNCATED AT 400 WORDS)
在I型糖尿病中替代胰岛素的一个主要问题是，目前不存在能够模拟健康胰腺基础胰岛素分泌的长效制剂。由于目前所有可用的中效或长效胰岛素制剂都有一个峰值作用曲线，所以每当在晚餐时注射此类胰岛素制剂时，午夜会出现胰岛素作用过量，黎明时胰岛素作用减弱。如果目标空腹血糖是强化胰岛素治疗所期望的接近正常血糖水平，晚餐时使用中效胰岛素很容易在傍晚早期导致低血糖，而在空腹状态下导致高血糖。I型糖尿病患者夜间血糖的问题因黎明现象和苏木杰现象而更加复杂。黎明现象是指胰岛素需求量在大约24:00至大约03:00之间开始下降，随后在大约05:00至大约08:00之间胰岛素需求量增加。黎明现象是肝脏（和肝外）胰岛素敏感性变化的结果，这最好归因于夜间生长激素分泌。黎明现象是几乎所有糖尿病患者都会出现的每日可重复事件。它对空腹高血糖的影响与糖尿病病程（呈反比）和糖化血红蛋白百分比（呈正比）相关。总体而言，据估计黎明现象对空腹高血糖的具体影响约为2 mM（约35 mg/dl），但由于前一晚注射的长效胰岛素制剂的影响，其影响可能会大得多。严格来说，苏木杰现象是指常规胰岛素诱发夜间低血糖后出现的空腹高血糖。由于目前晚餐时使用NPH/中效胰岛素的治疗方案会导致夜间高胰岛素血症，除了摄入过多葡萄糖来纠正低血糖外，夜间低血糖后很少会出现过度的空腹高血糖。然而，夜间低血糖可能很容易在当天晚些时候使血糖控制恶化，因为它会诱发长时间的低血糖后胰岛素抵抗，从而导致早餐后和上午晚些时候出现高血糖。对于夜间胰岛素治疗，重要的是要考虑胰岛素药代动力学、黎明现象和苏木杰现象等问题，以预防夜间低血糖和过度的空腹高血糖。（摘要截选至400字）
