Zuriaga María A, Fuster José J
Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
CIBER en Enfermedades Cardiovasculares (CIBER-CV), Madrid, Spain.
Diabetologia. 2025 May;68(5):920-929. doi: 10.1007/s00125-025-06393-8. Epub 2025 Mar 10.
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.
获得性体细胞突变的积累是衰老的自然结果,但这些突变在癌症之外的病理生理影响才刚刚开始被理解。大多数体细胞突变在功能上是中性的,但少数可能赋予干细胞竞争优势,驱动其克隆性扩增。当这种突变出现在造血干细胞中时,就会导致克隆性造血,即相当一部分血细胞起源于突变干细胞并共享相同的突变。不确定潜能克隆性造血(CHIP)是由髓系白血病相关体细胞突变驱动的克隆性造血的一个特定子集,通过加剧炎症反应,它与各种与年龄相关疾病的较高风险相关,尤其是心血管疾病。新出现的证据表明,CHIP也可能导致2型糖尿病及其一些并发症的发病机制。这篇综述综合了关于CHIP的现有知识及其作为2型糖尿病新风险因素的潜力,强调需要进一步研究以阐明这种关系,并探索其在制定2型糖尿病及相关疾病个性化预防护理策略方面的潜在价值。