Abstract
Introduction: Diabetic peripheral neuropathy (DPN) is a debilitating complication of type 2 diabetes mellitus (T2DM) that heavily impacts global patient quality of life and healthcare systems. Traditional management primarily centers on strict glycemic control and symptomatic pain relief, frequently overlooking the profound sleep-wake cycle disruptions and chronobiological misalignments highly prevalent in diabetic cohorts. Emerging data indicate that suppressed endogenous melatonin secretion severely exacerbates mitochondrial oxidative stress and impairs myelin sheath maintenance within peripheral nerves. Hypothesis: We propose “Neuro-Chronotherapeutic Resynchronization” as a distinct clinical paradigm that utilizes timed exogenous melatonin supplementation synchronized with targeted light therapy to downregulate peripheral neuroinflammation, restore Schwann cell mitochondrial plasticity, and alleviate nocturnal neuropathic pain. Testing the Hypothesis: We suggest randomized controlled trials comparing conventional analgesic therapy with an integrated chronotherapeutic program in patients with painful DPN, measuring changes in nocturnal pain scores, sleep architecture, markers of oxidative stress, and electroneuromyographic (ENMG) parameters. Implications: We propose a novel conceptual framework that integrates chronobiology into multidisciplinary neurodiabetology protocols, shifting sleep and circadian regulation from supportive hygiene advice to a central, disease-modifying neurological intervention.