Diabetes Metab Res Rev. 2026 Feb;42(2):e70137. doi: 10.1002/dmrr.70137.
ABSTRACT
Clonal haematopoiesis (CH) has been recognized as an important interface between chronic inflammation, metabolic dysfunction, and the heightened cardiovascular risk observed in type 2 diabetes (T2D). CH arises from somatic mutations that give haematopoietic stem cells a competitive advantage and drive the expansion of pro-inflammatory myeloid lineages. These mutant cells exhibit amplified IL-1β production, enhanced NLRP3-inflammasome activity, and increased chemokine signalling, thereby accelerating atherosclerosis, insulin resistance, and vascular inflammation. At the same time, metabolic disturbances characteristic of T2D promote clonal expansion by weakening normal stem cell fitness and modifying epigenetic regulation. This creates a self-reinforcing loop in which inflammation and metabolic stress sustain CH growth, while CH-derived myeloid cells worsen systemic and tissue-level inflammation. Such interactions may contribute not only to excess coronary disease and heart failure but also to microvascular complications through heightened myelopoiesis, neutrophil activation, and dysfunctional stem-cell mobilisation. This review integrates epidemiological, mechanistic, and experimental findings to present a unified model in which CH and diabetic metabolic stress act synergistically. We explore the shared pathways (niche remodelling, inflammatory memory, and metabolic rewiring) that underpin this bidirectional relationship and discusses how CH may differentially shape cardiometabolic outcomes. Future perspectives in this field are also discussed, including refining CH detection, integrating clone characteristics into risk stratification, and developing targeted therapies that disrupt the metabolic and inflammatory circuits supporting clonal expansion. Anti-inflammatory strategies and metabolic modulators may ultimately provide personalised approaches to reduce CH-associated cardiovascular risk in T2D.
PMID:41665140 | DOI:10.1002/dmrr.70137