Diabetes mellitus and glymphatic dysfunction: Roles for oxidative stress, mitochondria, circadian rhythm, artificial intelligence, and imaging

Abstract

Diabetes mellitus (DM) is a debilitating disorder that impacts all systems of the body and has been increasing in prevalence throughout the globe. DM represents a significant clinical challenge to care for individuals and prevent the onset of chronic disability and ultimately death. Underlying cellular mechanisms for the onset and development of DM are multi-factorial in origin and involve pathways associated with the production of reactive oxygen species and the generation of oxidative stress as well as the dysfunction of mitochondrial cellular organelles, programmed cell death, and circadian rhythm impairments. These pathways can ultimately involve failure in the glymphatic pathway of the brain that is linked to circadian rhythms disorders during the loss of metabolic homeostasis. New studies incorporate a number of promising techniques to examine patients with metabolic disorders that can include machine learning and artificial intelligence pathways to potentially predict the onset of metabolic dysfunction.

Keywords: Artificial intelligence; Circadian rhythm; Clock genes; Diabetes mellitus; magnetic resonance imaging; Glymphatic pathway; Mitochondria; Oxidative stress; Programmed cell death; Sleep fragmentation

Core Tip: Diabetes mellitus (DM) is a significant disorder across the globe affecting almost five hundred million individuals with significant disability that can involve musculoskeletal disease as well as cognitive loss. Multiple pathways can lead to DM that can affect the critical function of the brain’s glymphatic function, but the targeting of novel mechanisms tied to oxidative stress, mitochondrial dysfunction, circadian rhythm impairment, and new techniques such as artificial intelligence and imaging protocols offer exciting prospects for clinical care and treatment.