德国蒂宾根大学慕尼黑亥姆霍兹中心糖尿病研究与代谢疾病研究所Robert Wagner研究组，发现2型糖尿病高风险个体的基于病理生理学的亚表型。这一研究成果发表在2021年1月5日出版的《自然-医学》杂志上。
他们对来自广泛表型人群的口服糖耐量测试、MRI测量的体脂分布、肝脂肪含量和遗传风险进行了变量划分，从而发现了2型糖尿病的高风险人群，以确定六个不同的亚表型群。已鉴别的三种亚表型的血糖升高（第3、5和6组），但只有第5和3组中的个体有即将发生糖尿病的风险。相比之下，第6组中的人具有2型糖尿病的中度风险，但肾脏疾病和全因死亡率的风险增加。使用简单的拟人和血糖构建体在一个独立的队列中发现类似结果。
这项概念验证研究表明，在诊断2型糖尿病之前就存在病理生理学异质性，并着重指出了一组并发症风险增加而没有迅速发展为2型糖尿病的个体。
据介绍，中度高血糖状态表明发生2型糖尿病的风险增加。但是，目前对糖尿病的定义既不能反映2型糖尿病的病理生理亚表型，也不能预测未来的代谢轨迹。
附：英文原文
Title: Pathophysiology-based subphenotyping of individuals at elevated risk for type 2 diabetes
Author: Robert Wagner, Martin Heni, Adam G. Tabk, Jrgen Machann, Fritz Schick, Elko Randrianarisoa, Martin Hrab de Angelis, Andreas L. Birkenfeld, Norbert Stefan, Andreas Peter, Hans-Ulrich Hring, Andreas Fritsche
Issue&Volume: 2021-01-04
Abstract: The state of intermediate hyperglycemia is indicative of elevated risk of developing type 2 diabetes1. However, the current definition of prediabetes neither reflects subphenotypes of pathophysiology of type 2 diabetes nor is predictive of future metabolic trajectories. We used partitioning on variables derived from oral glucose tolerance tests, MRI-measured body fat distribution, liver fat content and genetic risk in a cohort of extensively phenotyped individuals who are at increased risk for type 2 diabetes2,3 to identify six distinct clusters of subphenotypes. Three of the identified subphenotypes have increased glycemia (clusters 3, 5 and 6), but only individuals in clusters 5 and 3 have imminent diabetes risks. By contrast, those in cluster 6 have moderate risk of type 2 diabetes, but an increased risk of kidney disease and all-cause mortality. Findings were replicated in an independent cohort using simple anthropomorphic and glycemic constructs4. This proof-of-concept study demonstrates that pathophysiological heterogeneity exists before diagnosis of type 2 diabetes and highlights a group of individuals who have an increased risk of complications without rapid progression to overt type 2 diabetes. Clustering of patients with prediabetes using simple clinical features reveals six distinct groups with differing risk of developing type 2 diabetes and its associated complications.
DOI: 10.1038/s41591-020-1116-9
Source: https://www.nature.com/articles/s41591-020-1116-9
Nature Medicine：《自然—医学》，创刊于1995年。隶属于施普林格·自然出版集团，最新IF：87.241
官方网址：https://www.nature.com/nm/
投稿链接：https://mts-nmed.nature.com/cgi-bin/main.plex
本期文章：《自然—医学》：Online/在线发表
