Diabetic cerebral microvascular disorder: from key pathologies to targeted interventions

BACKGROUND: Diabetes mellitus, a highly prevalent metabolic disorder worldwide, poses a severe threat to patient health primarily through its debilitating vascular complications. The cerebral microvasculature, essential for maintaining brain homeostasis and function, is particularly vulnerable to diabetic injury. However, diabetic cerebral microvascular disorder-a key contributor of neurological diseases like stroke, dementia, and cerebral small vessel disease-remains insufficiently characterized, and its pathophysiological mechanisms and therapeutic implications are not yet fully integrated. FINDINGS: This review comprehensively summarizes the structural and functional abnormalities of cerebral microcirculation in diabetes, encompassing pathological neovascularization, pathological remodeling, blood-brain barrier disruption, cerebrovascular reactivity impairment, capillary stalling, impaired autoregulation, and neurovascular uncoupling. These microvascular alterations are then examined in relation to major neurological diseases, such as stroke, cerebral small vessel disease, cognitive impairment, Parkinson's disease, and depression. Current and emerging interventions, ranging from lifestyle modification and glucose-lowering therapies to mechanism-targeted strategies, are also discussed. While this review covers cerebral microvascular alterations across diabetes subtypes, it should be noted that the majority of currently available evidence derives from studies in type 2 diabetes. CONCLUSIONS: This review provides a comprehensive synthesis of current knowledge on diabetic cerebral microvascular disorder, providing a framework for mechanistic research and supporting the clinical translation of microcirculation-targeted strategies for managing diabetes-related neurological complications.