Barnett A H
University of Birmingham and Birmingham Heartlands and Solihull NHS Trust (Teaching), Birmingham, UK.
Diabetes Obes Metab. 2006 Jul;8(4):388-95. doi: 10.1111/j.1463-1326.2005.00525.x.
Diabetes has reached epidemic proportions worldwide and most individuals with type 2 diabetes are obese. Therefore, there is a pressing need to carefully evaluate the impact of obesity on the efficacy of all diabetes therapies. Previously, obesity has been shown to adversely affect the efficacy of oral antidiabetic drugs; however, less is known about the impact of obesity on the properties of insulin and its analogues. As patients near target HbA1c, the more postprandial hyperglycaemia contributes to overall glycaemic control; thus, mealtime insulin, often supplied by a rapid-acting insulin analogue (RAI), becomes of increasing importance. As glycaemic targets set by professional bodies become lower and poor glycaemic control becomes increasingly less acceptable, earlier addition of RAIs to patients' treatment regimens may be required to meet these targets. However, in clinical practice, multiple barriers have challenged the acceptance and effective use of insulin therapy, including concern that it may cause weight gain. RAIs should ideally maintain their rapid-acting pharmacokinetic (PK) and pharmacodynamic (PD) profiles, irrespective of subcutaneous body fat, skin thickness and body mass index, in order to effectively meet intensive treatment goals. For example, initial PK/PD data with insulin glulisine in obese individuals suggest that this RAI may maintain its rapid-acting profile better than insulin lispro in the first 2 hours post-injection. However, data are preliminary and a thorough analysis of the impact of obesity on all RAIs in type 2 diabetes is warranted. This review focuses on the potential impact of obesity on RAIs and presents an overview of investigations in this area.
糖尿病在全球范围内已呈流行态势，大多数2型糖尿病患者都肥胖。因此，迫切需要仔细评估肥胖对所有糖尿病治疗疗效的影响。此前已表明，肥胖会对口服降糖药的疗效产生不利影响；然而，关于肥胖对胰岛素及其类似物特性的影响，人们了解得较少。随着患者接近糖化血红蛋白（HbA1c）目标值，餐后高血糖对总体血糖控制的贡献就越大；因此，通常由速效胰岛素类似物（RAI）提供的餐时胰岛素变得越来越重要。由于专业机构设定的血糖目标越来越低，血糖控制不佳越来越难以接受，可能需要在患者的治疗方案中更早地添加RAI，以实现这些目标。然而，在临床实践中，多种障碍对胰岛素治疗的接受度和有效使用提出了挑战，包括担心它可能导致体重增加。理想情况下，无论皮下脂肪、皮肤厚度和体重指数如何，RAI都应保持其速效药代动力学（PK）和药效学（PD）特性，以便有效地实现强化治疗目标。例如，在肥胖个体中使用赖谷胰岛素的初始PK/PD数据表明，这种RAI在注射后最初2小时内维持速效特性的效果可能优于赖脯胰岛素。然而，数据是初步的，有必要对肥胖对2型糖尿病所有RAI的影响进行全面分析。本综述重点关注肥胖对RAI的潜在影响，并概述该领域的研究情况。
