Diabetologia. 2025 Mar 10. doi: 10.1007/s00125-025-06393-8. Online ahead of print.
ABSTRACT
The accumulation of acquired somatic mutations is a natural consequence of ageing, but the pathophysiological implications of these mutations beyond cancer are only beginning to be understood. Most somatic mutations are functionally neutral, but a few may confer a competitive advantage to a stem cell, driving its clonal expansion. When such a mutation arises in haematopoietic stem cells, it leads to clonal haematopoiesis, in which a significant proportion of blood cells originate from the mutant stem cell and share the same mutation. Clonal haematopoiesis of indeterminate potential (CHIP), a specific subset of clonal haematopoiesis driven by myeloid leukaemia-related somatic mutations, has been linked to a higher risk of various age-related conditions, particularly CVD, by exacerbating inflammatory responses. Emerging evidence suggests that CHIP may also contribute to the pathogenesis of type 2 diabetes and some of its complications. This review synthesises current knowledge on CHIP and its potential as a novel risk factor for type 2 diabetes, highlighting the need for further research to clarify this relationship and to explore its potential value in developing personalised preventive care strategies for type 2 diabetes and related conditions.
PMID:40064675 | DOI:10.1007/s00125-025-06393-8