Integrated analysis of neuromuscular dysfunction and metabolic dysregulation in diabetic peripheral neuropathy: associations with digital deformities and clinical risk stratification in a case-control study

Esther Soler-Climent, Carmen Martinez-Corbalán, Erika Meléndez-Oliva, Jessica Román-Marroquí, Gema Prats-Boluda, Isabel Junquera-Godoy, Gemma González-Lorente, J.L. Martínez-de-Juan, Encarnación Agulló-García, Iciar Martin-LLaguno, Rosa María Cuadrado-Zaplana

<title>Abstract</title> Diabetic peripheral neuropathy (DPN), a common diabetes complication, arises from neuromuscular deterioration and metabolic dysregulation. These changes heighten the risk of hammer- and claw-toe deformities, disrupt foot biomechanics, and predispose patients to ulcers and amputations. Because DPN is multifactorial, integrating metabolic and neuromuscular indicators is critical.<bold>Objective</bold>: Identify predictors of digital deformities and diabetic-foot risk by combining surface electromyography (sEMG), hand dynamometry, bioimpedance, and intermuscular connectivity metrics—transfer entropy (TE) and normalised mutual information (NMI).<bold>Methods</bold>: In this case-control study, 65 adults (28 with type 2 diabetes, 37 controls) were assessed at a single centre. Outcomes included IWGDF foot-risk grade, bioimpedance-derived body composition, metabolic markers (HbA1c, triglyceride–glucose index), and neuromuscular tests (handgrip, sEMG, IMC/PDC). Correlations, ANOVA with post-hoc contrasts, and multiple imputation handled statistical analysis and missing data.<bold>Results</bold>: Greater waist circumference, higher BMI, and poorer metabolic profiles (glucose, HbA1c, triglycerides) were linked to elevated foot risk. Claw or hammer toes co-occurred with weaker handgrip, lower muscle quality, and reduced phase angle. Hand dynamometry proved a simple yet sensitive biomarker of neuromuscular decline. Findings suggest that interventions combining strict glycaemic control with strategies to enhance neuromuscular connectivity—such as functional electrical stimulation and targeted muscle strengthening—may attenuate deformity progression.<bold>Conclusions</bold>: DPN reflects an interplay of metabolic, biomechanical, and neuromuscular factors extending beyond the foot itself. An integrated clinical assessment that merges anthropometric, metabolic, and neuromuscular data can flag high-risk patients earlier. Holistic management—tight glycaemic control plus focused rehabilitation—offers potential to prevent digital deformities and downstream complications. Larger longitudinal studies are warranted to validate these approaches and optimise outcomes.