Department of Endocrinology and Internal Medicine, NBG/THG, Aarhus University Hospital, Aarhus, Denmark.
Diabetes Obes Metab. 2011 Jun;13(6):511-6. doi: 10.1111/j.1463-1326.2011.01373.x.
To combat diabetic complications strict glycaemic control is desirable in type 2 diabetes, but some patients are severely insulin resistant and it is not known whether high doses of insulin are effective. This study was designed to determine the acute dose-response effects of insulin in patients with type 2 diabetes and severe insulin resistance.
We included eight insulin-resistant (mean insulin dose: 186 IU/day; body mass index: 35) subjects with type 2 diabetes in a single-blinded, randomized crossover study. Each subject was studied on two occasions. On each occasion, subjects underwent two 3-h hyperinsulinaemic euglycaemic clamps. The subjects were randomized to two low-dose insulin infusions (0.5 and 1.5 mU/kg/min in random order) on one occasion and to two high-dose insulin infusions (3.0 and 5.0 mU/kg/min in random order) on another occasion.
On all occasions, steady-state glucose infusion rates (SSGIRs) were accomplished and we observed a clear dose-response relationship with GIR values of 0.4 ± 0.2 (s.e.), 2.6 ± 0.6, 3.7 ± 0.8 and 4.9 ± 0.9 mg/kg/min during the 0.5, 1.5, 3.0 and 5.0 mU/kg/min insulin infusions, respectively (p < 0.001). Likewise, there was a dose-dependent suppression of endogenous glucose production (EGP) (p < 0.009), plasma free fatty acids (FFAs) (p < 0.001) and plasma glucagon (p = 0.001).
Our results show that the insulin dose response in terms of GIR and EGP is preserved for insulin doses corresponding to >800 IU/day, suggesting effectiveness of very high insulin doses in severely insulin-resistant subjects.
在 2 型糖尿病中，严格的血糖控制是理想的，但有些患者存在严重的胰岛素抵抗，尚不清楚高剂量胰岛素是否有效。本研究旨在确定胰岛素在严重胰岛素抵抗的 2 型糖尿病患者中的急性剂量反应效应。
我们将 8 例胰岛素抵抗（平均胰岛素剂量：186IU/天；体重指数：35）的 2 型糖尿病患者纳入单盲、随机交叉研究。每位患者接受两次研究。在每一次研究中，患者都接受了两次 3 小时的高胰岛素-正常血糖钳夹。根据随机顺序，患者在一次研究中接受两种低剂量胰岛素输注（0.5 和 1.5mU/kg/min），在另一次研究中接受两种高剂量胰岛素输注（3.0 和 5.0mU/kg/min）。
在所有情况下，均达到稳态葡萄糖输注率（SSGIR），我们观察到明确的剂量反应关系，GIR 值分别为 0.4±0.2（s.e.）、2.6±0.6、3.7±0.8 和 4.9±0.9mg/kg/min，在 0.5、1.5、3.0 和 5.0mU/kg/min 的胰岛素输注时（p<0.001）。同样，内源性葡萄糖产生（EGP）（p<0.009）、血浆游离脂肪酸（FFA）（p<0.001）和血浆胰高血糖素（p=0.001）也存在剂量依赖性抑制。
我们的结果表明，GIR 和 EGP 的胰岛素剂量反应在对应于>800IU/天的胰岛素剂量下是保留的，这表明非常高剂量胰岛素在严重胰岛素抵抗的患者中是有效的。
