Clonal Hematopoiesis and Type 2 Diabetes: A Narrative Review

Clonal hematopoiesis (CH) refers to an expanded clonal hematopoietic cell population due to acquired mutations conferring a selective growth advantage. Once considered a premalignant hematological state, CH has now been causally associated with cardiovascular diseases (CVDs) and several aging-related clinical conditions. Emerging evidence suggests that CH is at the intersection of aging and metabolic disorders. CH carriers exhibit a higher risk of Type 2 diabetes, potentially through the obesity-inflammation-insulin resistance axis. Moreover, CH confers a higher risk of CVD and is associated with a poorer prognosis in patients with diabetes compared to noncarriers. In addition, CH has been associated with the development of microvascular complications, including retinopathy and kidney disease in patients with diabetes, although inconsistent findings exist. Preclinical studies found that antidiabetic medication metformin might slow down clonal expansion of CH, while clinical data suggest that anti-inflammatory medications confer better clinical outcomes for certain CH carriers, although their relevance for patients with diabetes remains to be elucidated. In this narrative review, we also briefly discuss the barriers to clinical adoption of CH detection and highlight the knowledge gaps that should be addressed in future work.