英国邓迪大学Ewan R. Pearson小组取得一项新突破。他们的最新研究揭示了2型糖尿病 (T2D)患者表型、疾病进展和药物反应异质性的关系。2022年5月9日出版的《自然-医学》杂志发表了这项成果。

在本项研究中，研究人员应用反向图嵌入方法定期收集来自苏格兰23,137名新诊断糖尿病患者的数据，以可视化T2D表型异质性，并使用模块化糖尿病多基因风险评分来深入了解潜在的生物过程。将疾病进展风险与胰岛素需求、慢性肾脏疾病、由糖尿病引起的视网膜病变和主要不良心血管事件相结合，研究人员展示了这些风险因素如何因患者表型而异。例如，有视网膜病变风险的患者在表型上与有心血管发病风险的患者不同。研究人员在英国生物银行和ADOPT临床试验中验证了该发现；同时，研究还表明糖尿病药物单一疗法的反应模式因不同药物而异。

总体而言，该分析揭示了在欧洲人群中，潜在的表型变异如何推动T2D发病并影响随后糖尿病治疗结果和药物反应；此外，该研究还证明需要将这些因素纳入T2D的个性化治疗方案。

研究人员表示，T2D是一种复杂的慢性疾病，其特征是存在相当强的表型异质性。

附：英文原文

Title: Heterogeneity in phenotype, disease progression and drug response in type 2 diabetes

Author: Nair, Anand Thakarakkattil Narayanan, Wesolowska-Andersen, Agata, Brorsson, Caroline, Rajendrakumar, Aravind Lathika, Hapca, Simona, Gan, Sushrima, Dawed, Adem Y., Donnelly, Louise A., McCrimmon, Rory, Doney, Alex S. F., Palmer, Colin N. A., Mohan, Viswanathan, Anjana, Ranjit M., Hattersley, Andrew T., Dennis, John M., Pearson, Ewan R.

Issue&Volume: 2022-05-09

Abstract: Type 2 diabetes (T2D) is a complex chronic disease characterized by considerable phenotypic heterogeneity. In this study, we applied a reverse graph embedding method to routinely collected data from 23,137 Scottish patients with newly diagnosed diabetes to visualize this heterogeneity and used partitioned diabetes polygenic risk scores to gain insight into the underlying biological processes. Overlaying risk of progression to outcomes of insulin requirement, chronic kidney disease, referable diabetic retinopathy and major adverse cardiovascular events, we show how these risks differ by patient phenotype. For example, patients at risk of retinopathy are phenotypically different from those at risk of cardiovascular events. We replicated our findings in the UK Biobank and the ADOPT clinical trial, also showing that the pattern of diabetes drug monotherapy response differs for different drugs. Overall, our analysis highlights how, in a European population, underlying phenotypic variation drives T2D onset and affects subsequent diabetes outcomes and drug response, demonstrating the need to incorporate these factors into personalized treatment approaches for the management of T2D. A new analysis of patients newly diagnosed with diabetes uses a data dimenionality reduction approach to understand how phenotypic variation drives diseaese onset, clinical outcomes and responses to glycemic-lowering medications.

DOI: 10.1038/s41591-022-01790-7

Source: https://www.nature.com/articles/s41591-022-01790-7