Author:
Wang Jiexun,Liu Jian-Jun,Gurung Resham L.,Liu Sylvia,Lee Janus,M Yiamunaa,Ang Keven,Shao Yi Ming,Tang Justin I-Shing,Benke Peter I.,Torta Federico,Wenk Markus R.,Tavintharan Subramaniam,Tang Wern Ee,Sum Chee Fang,Lim Su Chi
Abstract
Abstract
Aims/hypothesis
We sought to subtype South East Asian patients with type 2 diabetes by de novo cluster analysis on clinical variables, and to determine whether the novel subgroups carry distinct genetic and lipidomic features as well as differential cardio-renal risks.
Methods
Analysis by k-means algorithm was performed in 687 participants with recent-onset diabetes in Singapore. Genetic risk for beta cell dysfunction was assessed by polygenic risk score. We used a discovery–validation approach for the lipidomics study. Risks for cardio-renal complications were studied by survival analysis.
Results
Cluster analysis identified three novel diabetic subgroups, i.e. mild obesity-related diabetes (MOD, 45%), mild age-related diabetes with insulin insufficiency (MARD-II, 36%) and severe insulin-resistant diabetes with relative insulin insufficiency (SIRD-RII, 19%). Compared with the MOD subgroup, MARD-II had a higher polygenic risk score for beta cell dysfunction. The SIRD-RII subgroup had higher levels of sphingolipids (ceramides and sphingomyelins) and glycerophospholipids (phosphatidylethanolamine and phosphatidylcholine), whereas the MARD-II subgroup had lower levels of sphingolipids and glycerophospholipids but higher levels of lysophosphatidylcholines. Over a median of 7.3 years follow-up, the SIRD-RII subgroup had the highest risks for incident heart failure and progressive kidney disease, while the MARD-II subgroup had moderately elevated risk for kidney disease progression.
Conclusions/interpretation
Cluster analysis on clinical variables identified novel subgroups with distinct genetic, lipidomic signatures and varying cardio-renal risks in South East Asian participants with type 2 diabetes. Our study suggests that this easily actionable approach may be adapted in other ethnic populations to stratify the heterogeneous type 2 diabetes population for precision medicine.
Graphical abstract
Funder
Khoo Teck Puat hospital STAR grant
Singapore National Medical Research Council
Publisher
Springer Science and Business Media LLC
Subject
Endocrinology, Diabetes and Metabolism,Internal Medicine
Cited by
9 articles.
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