Franks Paul W, Rich Stephen S, Linder Barbara, Zaghloul Norann A, Cefalu William T
Department of Clinical Sciences, Lund University, Helsingborg Hospital, Helsingborg 251 87, Sweden.
Department of Genome Sciences, University of Virginia, Charlottesville, VA 22908, USA.
J Clin Endocrinol Metab. 2025 Feb 18;110(3):601-610. doi: 10.1210/clinem/dgae844.
The current classification of diabetes had its genesis over 85 years ago, when individuals with diabetes were first subclassified into insulin sensitive and insulin insensitive states based on the response to an oral glucose tolerance test. About 35 years later, the contemporary classifications of type 1 and type 2 diabetes were coined. Today's evidence, however, suggests that multiple etiologic and pathogenic processes lead to both type 1 and type 2 diabetes, reflecting significant heterogeneity in factors associated with initiation, progression, and clinical presentation of each disorder of glucose homeostasis. Further, the current classification fails to recognize what is currently defined as "atypical" diabetes. Heterogeneity of diabetes continues through the life-course of an individual, with modification of prognosis risk (eg, diabetic complications) altered by genetics, life experience, comorbidities, and therapy. Understanding the sources of heterogeneity in diabetes will likely improve diagnosis, prevention, treatment, and prediction of complications in both the medical and public health settings. Such knowledge will help inform progress in the emerging era of precision diabetes medicine. This article presents NIDDK's Heterogeneity of Diabetes Initiative and a corresponding roadmap for future research in type 2 diabetes heterogeneity.
当前的糖尿病分类起源于85多年前，当时糖尿病患者首次根据口服葡萄糖耐量试验的反应被细分为胰岛素敏感和胰岛素不敏感状态。大约35年后，1型和2型糖尿病的现代分类被创造出来。然而，如今的证据表明，多种病因和致病过程会导致1型和2型糖尿病，这反映出与葡萄糖稳态的每种疾病的起始、进展和临床表现相关的因素存在显著异质性。此外，目前的分类未能识别目前被定义为“非典型”的糖尿病。糖尿病的异质性在个体的生命过程中持续存在，预后风险（如糖尿病并发症）会因遗传、生活经历、合并症和治疗而改变。了解糖尿病异质性的来源可能会改善医疗和公共卫生环境中糖尿病的诊断、预防、治疗以及并发症的预测。这些知识将有助于为精准糖尿病医学的新兴时代提供信息。本文介绍了美国国立糖尿病、消化和肾脏疾病研究所的糖尿病异质性倡议以及2型糖尿病异质性未来研究的相应路线图。
