Lin Hong, Ding Yilan, Jia Xiaojing, Gu Xuejiang, Wang Shuangyuan, Li Mian, Xu Yu, Xu Min, Mu Yiming, Chen Lulu, Zeng Tianshu, Shi Lixin, Su Qing, Chen Yuhong, Yu Xuefeng, Yan Li, Qin Guijun, Wan Qin, Chen Gang, Tang Xulei, Gao Zhengnan, Shen Feixia, Hu Ruying, Luo Zuojie, Qin Yingfen, Chen Li, Hou Xinguo, Huo Yanan, Li Qiang, Wang Guixia, Zhang Yinfei, Liu Chao, Wang Youmin, Wu Shengli, Yang Tao, Deng Huacong, Huang Feiyue, Xu Xingkun, Wei Huapeng, Zheng Jie, Wang Tiange, Zhao Zhiyun, Zhao Jiajun, Ning Guang, Wang Weiqing, Bi Yufang, Lu Jieli
Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai National Clinical Research Center for Endocrine and Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Digital Medicine Innovation Center, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China.
The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Cell Rep Med. 2025 Jul 15;6(7):102212. doi: 10.1016/j.xcrm.2025.102212. Epub 2025 Jul 2.
Prediabetes, an intermediate stage of developing diabetes, exhibits considerable phenotypic heterogeneity. Here, we apply the Discriminative Dimensionality Reduction Tree (DDRTree) algorithm to explore prediabetes heterogeneity in 55,777 participants from the China Cardiometabolic Disease and Cancer Cohort (4C) study. Based on 12 clinically available variables, we identify four distinct phenotypes and observe differential risks of type 2 diabetes mellitus (T2DM), chronic kidney disease (CKD), and cardiovascular disease (CVD). Phenotype 4, characterized by hyperglycemia, insulin resistance, obesity, elevated triglycerides, and liver enzymes, has the highest T2DM risk, while phenotype 3, predominantly driven by obesity, insulin resistance, hyperglycemia, and dyslipidemia, has the highest CKD risk. Phenotypes 3 and 4 show higher CVD risk, with distinct distributions of CVD subtypes. These findings are validated in the external cohort SN_2009-2021, and a user-friendly online tool is provided for individual risk prediction. Overall, our study elucidates the intricate dynamics of prediabetes progression, aiding in personalized management for prediabetes care.
糖尿病前期是糖尿病发展的中间阶段，表现出相当大的表型异质性。在此，我们应用判别降维树（DDRTree）算法，在中国心血管代谢疾病与癌症队列（4C）研究的55777名参与者中探索糖尿病前期的异质性。基于12个临床可用变量，我们识别出四种不同的表型，并观察到2型糖尿病（T2DM）、慢性肾脏病（CKD）和心血管疾病（CVD）的不同风险。表型4以高血糖、胰岛素抵抗、肥胖、甘油三酯升高和肝酶升高为特征，具有最高的T2DM风险，而主要由肥胖、胰岛素抵抗、高血糖和血脂异常驱动的表型3具有最高的CKD风险。表型3和4显示出较高的CVD风险，且CVD亚型分布不同。这些发现在外围队列SN_2009 - 2021中得到验证，并提供了一个用户友好的在线工具用于个体风险预测。总体而言，我们的研究阐明了糖尿病前期进展的复杂动态，有助于糖尿病前期护理的个性化管理。
