Russell-Jones D, Danne T, Hermansen K, Niswender K, Robertson K, Thalange N, Vasselli J R, Yildiz B, Häring H U
Diabetes and Endocrinology, Royal Surrey County Hospital and University of Surrey, Guildford, UK.
Diabetes-Zentrum für Kinder und Jugendliche, Kinderkrankenhaus auf der Bult, Hannover, Germany.
Diabetes Obes Metab. 2015 Oct;17(10):919-27. doi: 10.1111/dom.12493. Epub 2015 Aug 11.
Insulin therapy is often associated with adverse weight gain. This is attributable, at least in part, to changes in energy balance and insulin's anabolic effects. Adverse weight gain increases the risk of poor macrovascular outcomes in people with diabetes and should therefore be mitigated if possible. Clinical studies have shown that insulin detemir, a basal insulin analogue, exerts a unique weight-sparing effect compared with other basal insulins. To understand this property, several hypotheses have been proposed. These explore the interplay of efferent and afferent signals between the muscles, brain, liver, renal and adipose tissues in response to insulin detemir and comparator basal insulins. The following models have been proposed: insulin detemir may reduce food intake through direct or indirect effects on the central nervous system (CNS); it may have favourable actions on hepatic glucose metabolism through a selective effect on the liver, or it may influence fluid homeostasis through renal effects. Studies have consistently shown that insulin detemir reduces energy intake, and moreover, it is clear that this shift in energy balance is not a consequence of reduced hypoglycaemia. CNS effects may be mediated by direct action, by indirect stimulation by peripheral mediators and/or via a more physiological counter-regulatory response to insulin through restoration of the hepatic-peripheral insulin gradient. Although the precise mechanism remains unclear, it is likely that the weight-sparing effect of insulin detemir can be explained by a combination of mechanisms. The evidence for each hypothesis is considered in this review.
胰岛素治疗常常与不良体重增加相关。这至少部分归因于能量平衡的变化以及胰岛素的合成代谢作用。不良体重增加会增加糖尿病患者发生不良大血管结局的风险，因此应尽可能减轻。临床研究表明，基础胰岛素类似物地特胰岛素与其他基础胰岛素相比具有独特的体重减轻作用。为了解这一特性，人们提出了几种假说。这些假说探讨了肌肉、大脑、肝脏、肾脏和脂肪组织之间传出和传入信号在对地特胰岛素和对照基础胰岛素的反应中的相互作用。已提出以下模型：地特胰岛素可能通过对中枢神经系统（CNS）的直接或间接作用来减少食物摄入；它可能通过对肝脏的选择性作用对肝葡萄糖代谢产生有利作用，或者它可能通过肾脏作用影响液体平衡。研究一直表明地特胰岛素会减少能量摄入，而且很明显这种能量平衡的变化不是低血糖减少的结果。中枢神经系统效应可能由直接作用、外周介质的间接刺激和/或通过恢复肝 - 外周胰岛素梯度对胰岛素产生更生理性的反调节反应介导。尽管确切机制尚不清楚，但地特胰岛素的体重减轻作用可能可以通过多种机制的组合来解释。本综述考虑了每个假说的证据。
