Integrated analysis of neuromuscular dysfunction and metabolic dysregulation in diabetic peripheral neuropathy:...

Diabetic peripheral neuropathy (DPN) is a multifactorial complication in which metabolic dysregulation, altered body composition, and neuromuscular impairment may contribute to structural foot alterations and ulceration risk. These domains are often studied separately, limiting understanding of their combined relationship with digital deformities and diabetic-foot risk.

To evaluate exploratory associations between digital deformities, diabetic-foot risk, and integrated anthropometric, metabolic, bioimpedance-derived, functional, and neuromuscular markers.

This single-center case-control study included 65 adults: 28 with type 2 diabetes and 37 non-diabetic controls. Assessments included anthropometry, bioimpedance-derived parameters - phase angle (PhA), ECW/TBW ratio, and muscle quality - handgrip dynamometry, HbA1c, and the triglyceride-glucose (TyG) index. Diabetic-foot risk was classified according to IWGDF criteria in participants with type 2 diabetes. Analyses included Shapiro-Wilk tests, Student's t-test or Mann-Whitney U test, Pearson or Spearman correlations, and one-way ANOVA with Tukey post-hoc tests. Missing data were below 5% and were imputed.

Diabetic-foot risk correlated with waist circumference (r = 0.443, p < 0.001), BMI (r = 0.333, p = 0.005), HbA1c (r = 0.560, p < 0.001), and TyG index (r = 0.454, p < 0.001). Digital deformities were associated with fasting glucose (r = 0.573, p < 0.001), HbA1c (r = 0.560, p < 0.001), and TyG index (r = 0.565, p < 0.001). Inverse associations were observed for handgrip strength (r = -0.340, p = 0.004), muscle quality (r = -0.311, p = 0.009), and PhA (r = -0.285, p = 0.018). Exploratory subgroup analyses showed differences across analytical risk strata for PhA (F = 6.99, p = 0.002), muscle quality (F = 6.99, p = 0.002), and handgrip strength (F = 4.04, p = 0.022).

Digital deformities and diabetic-foot risk in DPN were associated with combined metabolic, bioimpedance-derived, and systemic neuromuscular alterations. Handgrip strength and bioimpedance-derived parameters showed exploratory associations with risk and deformities; however, their role as complementary assessment measures requires confirmation in larger longitudinal studies with adjusted models.