Baylor Endocrine Center, Dallas, Texas, USA.
Diabetes Metab Syndr Obes. 2012;5:11-9. doi: 10.2147/DMSO.s266980. Epub 2012 Jan 10.
The risk for developing type 2 diabetes (T2DM) is greater among obese individuals. Following onset of the disease, patients with T2DM become more likely to be afflicted with diabetic micro- and macrovascular complications. Decreasing body weight has been shown to lower glycosylated hemoglobin and improve other metabolic parameters in patients with T2DM. Medications used to lower blood glucose may increase body weight in patients with T2DM and this has been repeatedly shown to be the case for conventional, human insulin formulations. Insulin detemir is a neutral, soluble, long-acting insulin analog in which threonine-30 of the insulin B-chain is deleted, and the C-terminal lysine is acetylated with myristic acid, a C14 fatty acid chain. Insulin detemir binds to albumin, a property that enhances its pharmacokinetic/pharmacodynamic profile. Results from clinical trials have demonstrated that treatment with insulin detemir is associated with less weight gain than either insulin glargine or neutral protamine Hagedorn insulin. There are many potential reasons for the lower weight gain observed among patients treated with insulin detemir, including lower risk for hypoglycemia and therefore decreased defensive eating due to concern about this adverse event, along with other effects that may be related to the albumin binding of this insulin that may account for lower within-patient variability and consistent action. These might include faster transport across the blood-brain barrier, induction of satiety signaling in the brain, and preferential inhibition of hepatic glucose production versus peripheral glucose uptake. Experiments in diabetic rats have also indicated that insulin detemir increases adiponectin levels, which is associated with both weight loss and decreased eating.
肥胖个体发生 2 型糖尿病（T2DM）的风险更高。在疾病发作后，T2DM 患者更有可能患上糖尿病的微血管和大血管并发症。体重减轻已被证明可降低 T2DM 患者的糖化血红蛋白并改善其他代谢参数。用于降低血糖的药物可能会使 T2DM 患者的体重增加，这已反复证明是常规人胰岛素制剂的情况。地特胰岛素是一种中性、可溶性、长效胰岛素类似物，其中胰岛素 B 链的苏氨酸-30 被删除，C 末端赖氨酸被豆蔻酸酰化，豆蔻酸是一种 C14 脂肪酸链。地特胰岛素与白蛋白结合，这一特性增强了其药代动力学/药效学特征。临床试验结果表明，与甘精胰岛素或中性鱼精蛋白胰岛素相比，地特胰岛素治疗与体重增加减少相关。在接受地特胰岛素治疗的患者中观察到体重增加较少可能有许多潜在原因，包括低血糖风险较低，因此由于担心这种不良事件而减少防御性进食，以及与该胰岛素与白蛋白结合相关的其他可能导致患者内变异性降低和一致作用的效应。这些可能包括更快地穿过血脑屏障的转运、在大脑中诱导饱腹感信号以及优先抑制肝葡萄糖生成而不是外周葡萄糖摄取。糖尿病大鼠的实验还表明，地特胰岛素可增加脂联素水平，这与体重减轻和减少进食有关。
