McCarthy Mark I
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Old Road, Headington, Oxford, OX3 7LJ, UK.
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Diabetologia. 2017 May;60(5):793-799. doi: 10.1007/s00125-017-4210-x. Epub 2017 Feb 7.
The current focus on delivery of personalised (or precision) medicine reflects the expectation that developments in genomics, imaging and other domains will extend our diagnostic and prognostic capabilities, and enable more effective targeting of current and future preventative and therapeutic options. The clinical benefits of this approach are already being realised in rare diseases and cancer but the impact on management of complex diseases, such as type 2 diabetes, remains limited. This may reflect reliance on inappropriate models of disease architecture, based around rare, high-impact genetic and environmental exposures that are poorly suited to our emerging understanding of type 2 diabetes. This review proposes an alternative 'palette' model, centred on a molecular taxonomy that focuses on positioning an individual with respect to the major pathophysiological processes that contribute to diabetes risk and progression. This model anticipates that many individuals with diabetes will have multiple parallel defects that affect several of these processes. One corollary of this model is that research efforts should, at least initially, be targeted towards identifying and characterising individuals whose adverse metabolic trajectory is dominated by perturbation in a restricted set of processes.
当前对个性化（或精准）医疗的关注反映出一种期望，即基因组学、影像学及其他领域的发展将拓展我们的诊断和预后能力，并使当前及未来的预防和治疗选择更有效地靶向目标。这种方法的临床益处已在罕见病和癌症领域得以实现，但对诸如2型糖尿病等复杂疾病管理的影响仍然有限。这可能反映出对不恰当疾病结构模型的依赖，该模型围绕罕见、高影响的遗传和环境暴露构建，而这些暴露并不适合我们对2型糖尿病的新认识。本综述提出了一种替代性的“调色板”模型，该模型以分子分类学为核心，重点在于根据导致糖尿病风险和进展的主要病理生理过程来定位个体。该模型预计，许多糖尿病患者会有多个平行缺陷，影响这些过程中的若干个过程。此模型的一个推论是，研究工作至少在初期应致力于识别和描述那些不良代谢轨迹主要由一组受限过程中的扰动所主导的个体。
