[Diabetes-driven hematopoietic remodeling and metabolic memory]

Diabetes mellitus is a metabolic disorder characterized by chronic hyperglycemia and is accompanied by a range of complications affecting the cardiovascular system, kidneys, retina, and nervous system. In the context of diabetes, the bone marrow (BM) and hematopoietic stem and progenitor cells (HSPCs) are not only targets of metabolic dysregulation, but also play an active role in driving chronic inflammation and tissue damage. Prolonged hyperglycemia markedly disrupts HSPC bone marrow niche homeostasis, leading to decreased HSPC numbers, impaired mobilization, and biased differentiation. As a result, the hematopoietic system shifts from supporting tissue repair and immune homeostasis to driving pro-inflammatory hematopoiesis. Diabetes induces metabolic reprogramming and epigenetic remodeling in HSPCs, as well as in supportive cells within the BM niche. Aberrant metabolic states interact with epigenetic regulation to reshape transcriptional programs in HSPCs, thereby establishing a stable inflammatory hematopoietic phenotype. In addition, diabetes-associated trained immunity enables HSPCs to acquire pro-inflammatory memory and transmit this bias to their myeloid progeny, providing a mechanistic link between metabolic memory and chronic inflammation. This review systematically summarizes abnormalities in the number and function of hematopoietic cells under diabetic conditions, as well as the roles of metabolic reprogramming and epigenetic regulation in hematopoietic imbalance. It focuses on recent progress in diabetes-associated hematopoietic remodeling and metabolic memory, aiming to provide a hematopoietic perspective for understanding the pathophysiological processes underlying diabetes-induced multi-organ alterations and to offer a reference for exploring potential hematopoietic intervention targets for diabetic complications.