The effects of diabetes on the glymphatic system: recent advances and mechanistic insights

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by persistent hyperglycemia and is associated with a variety of systemic complications, including cardiovascular diseases, neuropathies, and cognitive decline. An emerging area of interest is the impact of diabetes on the glymphatic system, a waste clearance system in the central nervous system (CNS) that plays a critical role in maintaining brain homeostasis. Recent studies suggest that glymphatic dysfunction may contribute to the pathogenesis of diabetic encephalopathy, a condition characterized by cognitive deficits and an increased risk of neurodegenerative diseases such as Alzheimer's disease (AD). This review provides a review of the effects of diabetes on the glymphatic system, drawing on a broad spectrum of recent research. We examine the mechanistic underpinnings of glymphatic impairment in diabetes, the role of hyperglycemia and insulin resistance, and the potential therapeutic implications. We also explore the broader context of diabetes-related CNS changes, including the impact on cerebrovascular function, neuroinflammation, and sleep disturbances. Finally, we discuss future directions in this rapidly evolving field, highlighting the need for further research into the glymphatic system as a therapeutic target in diabetes.