Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Medicine, Nephrology and Clinical Chemistry, University of Tübingen, Otfried-Müller-Strasse 10, Tübingen, Germany.
Diabetes Obes Metab. 2009 Nov;11(11):1017-26. doi: 10.1111/j.1463-1326.2009.01085.x. Epub 2009 Jul 23.
The long-acting insulin analogue detemir (Levemir) has structural and physicochemical properties which differ from human insulin. The aim of the present study was to test whether this leads to altered hormone and symptom response during hypoglycaemia.
12 healthy subjects [6f/6m, age 32 +/- 6 years (mean +/- s.d.), body mass index (BMI) 24.2 +/- 2.5 kg/m(2)] underwent a 200-min stepwise hypoglycaemic clamp (45 min steps of 4.4, 3.7, 3.0 and 2.3 mmol/l) with either detemir or human insulin in random order. A bolus of detemir (660 mU/kg) or human insulin (60 mU/kg) was given before insulin was infused at a rate of 5 (detemir) or 2 (human insulin) mU/kg/min. Blood was drawn and a semi-quantitative symptom questionnaire was administered before and after each plateau of the hypoglycaemic clamp. Cognitive function was assessed during each step.
Blood glucose levels and glucose infusion rates were comparable with detemir and human insulin. The total symptom score was higher with detemir during the 3 and 2.3 mmol glucose step compared to human insulin (p = 0.048). Especially sweating was increased with detemir (p = 0.02) with an earlier and faster increase during the clamp (interaction insulin x time: p = 0.04). No significant differences between detemir and human insulin in cortisol, norepinephrine, epinephrine, glucagon, growth hormone, lactate or free fatty acid (FFA) levels during hypoglycaemia were observed, and there were no significant differences in cognitive function tests.
Insulin detemir increased symptom awareness during hypoglycaemia compared to human insulin in healthy individuals, whereas counter-regulatory hormone response and cognitive function were unaltered.
长效胰岛素类似物地特胰岛素（来得时）在结构和理化性质上与人胰岛素不同。本研究旨在检测低血糖时激素和症状反应是否发生改变。
12 名健康受试者[6 女/6 男，年龄 32 ± 6 岁（均值 ± 标准差），体重指数（BMI）24.2 ± 2.5 kg/m2]按随机顺序分别接受地特胰岛素或人胰岛素 200 分钟逐步低血糖钳夹试验（45 分钟 4.4、3.7、3.0 和 2.3 mmol/l 各 4 个阶段）。地特胰岛素（660 mU/kg）或人胰岛素（60 mU/kg）推注后，以 5（地特胰岛素）或 2（人胰岛素）mU/kg/min 的速度输注胰岛素。每次低血糖钳夹平台前和后采血，半定量症状问卷评估。每次阶段检测认知功能。
地特胰岛素和人胰岛素组血糖水平和葡萄糖输注率相似。与地特胰岛素相比，人胰岛素组在 3 和 2.3 mmol 葡萄糖阶段总症状评分更高（p = 0.048）。地特胰岛素组（p = 0.02）出汗更多，低血糖钳夹时更快更早增加（胰岛素 x 时间交互作用：p = 0.04）。低血糖时，地特胰岛素和人胰岛素组皮质醇、去甲肾上腺素、肾上腺素、胰高血糖素、生长激素、乳酸和游离脂肪酸（FFA）水平无显著差异，认知功能测试也无显著差异。
与健康个体的人胰岛素相比，地特胰岛素增加低血糖时的症状感知，而激素的代偿反应和认知功能无改变。
