ACCELERATING PERIPHERAL NEURODEGENERATION: THE IMPACT OF METABOLIC-ASSOCIATED FATTY LIVER DISEASE ON THE STRUCTURAL PROGRESSION OF DIABETIC SENSORIMOTOR POLYNEUROPATHY

Diabetic sensorimotor polyneuropathy remains a leading catalyst for lower extremity amputations, conventionally attributed to the isolated neurotoxic effects of advanced glycation end-products and the hyperactive polyol pathway. The recent reclassification of non-alcoholic fatty liver disease to metabolic-associated fatty liver disease (MAFLD) introduces a profound systemic dimension to diabetic microvascular complications, positioning the steatotic liver as an active orchestrator of distant axonal degeneration. This prospective, single-center observational study was designed to quantify the specific neurodegenerative velocity induced by MAFLD in patients with established Type 2 Diabetes Mellitus. An analytical cohort of 310 adult diabetic patients was stratified based on the presence or absence of concomitant MAFLD and continuously tracked over a 36-month longitudinal timeline. Comprehensive electroneuromyography, quantitative sensory testing, and biochemical assays mapped the structural and functional decline of the peripheral nervous system. The longitudinal data exposed an exceptionally aggressive neuropathic phenotype within the dual-pathology cohort. Patients afflicted with MAFLD demonstrated a precipitous annual reduction in peroneal motor nerve conduction velocity of 2.4 ± 0.6 m/s, severely outpacing the 0.9 ± 0.4 m/s deterioration recorded in the isolated diabetes group. Similarly, the sural sensory nerve action potential amplitude collapsed at a 2.7-fold higher rate in the presence of hepatic steatosis. Advanced hepatic fibrogenesis, objectively quantified via transient elastography and the FIB-4 index, maintained a dominant independent inverse correlation with peripheral myelination integrity and conduction velocities (r = -0.75, p < 0.001). The MAFLD-burdened liver continuously discharges lipotoxic ceramides and pro-inflammatory hepatokines into the systemic circulation, severely compromising the vasa nervorum and directly inducing Schwann cell apoptosis. Integrating transient elastography into neurological risk stratification paradigms is an absolute clinical imperative, allowing practitioners to identify high-risk peripheral degeneration profiles and aggressively initiate targeted metabolic interventions before irreversible axonal death occurs.