Integrated Approaches to Diabetes-related Vascular and Neurological Complications: Advances and Challenges

Abstract

Diabetes mellitus is a major global health burden, with prevalence predicted to spiral exponentially over the next few decades. The chronic metabolic syndrome that this and similar conditions represent is associated with a plethora of vascular and nerve complications that account for substantial morbidity, mortality, and healthcare expenditures. Hyperglycemia-mediated endothelial dysfunction, through its vascular sequelae—microvascular and macrovascular complications—defines angiopathy (e.g., retinopathy, nephropathy) and hypertension (as an example of peripheral arteriolosclerosis), which are pathways for vascular complications. Likewise, neurological complications, including peripheral neuropathy and the comorbid cognitive reserve and information on autonomic dysfunction, are thought to integrate through mechanisms such as axonal transport dysfunction, demyelination, neuronal apoptosis, or Schwann cell dysfunction. Predisposing factors for the coexistence of both complications are overlapping and stem from common pathophysiological pathways, like chronic hyperglycemia and advanced glycation end products (AGEs), emphasizing the need for synergistic therapeutic strategies. Health disparities and limited access to early diagnosis and treatment in low-resource settings exacerbate the global burden of diabetes-related complications, necessitating equitable healthcare solutions. New and improved diagnostic techniques, including non-invasive vascular imaging, neuroimaging biomarkers, as well as functional vascular and neurological assessments, have improved early detection. Concurrently, new therapeutic advances such as gene therapy, stem cell-based therapies, RNA therapeutic technologies, and nanomedicine will change the game in the management of diabetic complications. Emerging approaches rooted in personalized medicine also offer promising avenues for tailoring treatments to individual patient needs while addressing genetic, environmental, and lifestyle factors. A comprehensive review of diabetes-induced vascular and neuropathological complications based on epidemiology, pathophysiology, diagnostic approaches, and treatment will be presented in the following tutorial review. It is further an overview from a translational perspective and calls for the global implementation of personalized medicine efforts to reduce the global diabetes burden.