Dagogo-Jack S, Askari H, Morrill B, Lehner L L, Kim B, Sha X
Department of Medicine, University of Mississippi Medical Center, Jackson 39216, USA.
Diabetes Obes Metab. 2000 Dec;2(6):373-83. doi: 10.1046/j.1463-1326.2000.00109.x.
Glargine, a product of recombinant technology, has different structural and physicochemical properties compared with native human insulin. We determined whether such differences are associated with alterations in the responses to hypoglycaemia induced by glargine.
Nineteen adults (six healthy and 13 with type 1 diabetes) underwent a 5-h hyperinsulinaemic (2 mU/kg/min(-1)) stepped hypoglycaemic clamps (hourly targets of 4.7, 4.2, 3.6, 3.1 and 2.5 mmol/l, respectively) on two occasions using intravenous infusion of regular human insulin or glargine, in random sequence. Hypoglycaemic symptoms, counter-regulatory hormones and glucose disposal rates were assessed at intervals throughout the clamps. A 1-week 'wash out' period was observed between studies.
The peak total symptoms scores (mean +/- s.e.m.) at nadir blood glucose (2.5 mmol/1) were 18.83 +/- 2.68 (healthy) and 17.46 +/- 3.62 (diabetic) during regular insulin, and 18.50 +/- 3.20 (healthy) and 19.08 +/- 3.83 (diabetic) during glargine infusion. The peak epinephrine levels during hypoglycaemia were 767.8 +/- 140.4 pg/ml (regular insulin) and 608.8 +/- 129.9 pg/ml (glargine) among healthy subjects, and 332.5 +/- 54.8 pg/ml (regular insulin) and 321.8 +/- 67.4 pg/ml (glargine) in diabetic patients. Diabetic patients had blunted glucagon responses during hypoglycaemia with either insulin. Both insulins also elicited similar rates of glucose disposal.
We conclude that insulin glargine and regular human insulin elicit comparable symptomatic and counter-regulatory hormonal responses during hypoglycaemia in healthy or diabetic subjects, and induce similar rates of glucose disposal. Since glargine is designed for subcutaneous (s.c.) use, it is possible (though unlikely) that our findings obtained using an intravenous protocol could differ from responses to hypoglycaemia induced by the s.c. route.
甘精胰岛素是一种重组技术产品，与天然人胰岛素相比，具有不同的结构和理化性质。我们确定了这些差异是否与甘精胰岛素诱导的低血糖反应改变有关。
19名成年人（6名健康者和13名1型糖尿病患者）分两次接受5小时的高胰岛素血症（2 mU/kg/min(-1)）阶梯式低血糖钳夹试验（每小时目标血糖分别为4.7、4.2、3.6、3.1和2.5 mmol/l），随机顺序静脉输注常规人胰岛素或甘精胰岛素。在整个钳夹过程中间隔评估低血糖症状、反调节激素和葡萄糖处置率。两次研究之间观察1周的“洗脱”期。
在血糖最低点（2.5 mmol/l）时，常规胰岛素组健康受试者和糖尿病患者的总症状评分峰值（均值±标准误）分别为18.83±2.68和17.46±3.62，甘精胰岛素输注组分别为18.50±3.20和19.08±3.83。健康受试者低血糖期间肾上腺素峰值水平在常规胰岛素组为767.8±140.4 pg/ml，甘精胰岛素组为608.8±129.9 pg/ml；糖尿病患者在常规胰岛素组为332.5±54.8 pg/ml，甘精胰岛素组为321.8±67.4 pg/ml。糖尿病患者在低血糖期间使用任何一种胰岛素时胰高血糖素反应均减弱。两种胰岛素引起的葡萄糖处置率也相似。
我们得出结论，在健康或糖尿病受试者低血糖期间，甘精胰岛素和常规人胰岛素引起的症状性和反调节激素反应相当，且诱导的葡萄糖处置率相似。由于甘精胰岛素设计用于皮下注射，使用静脉输注方案获得的我们的研究结果可能（尽管不太可能）与皮下注射途径诱导的低血糖反应不同。
