Supplementary file 2_Neurological manifestations in metabolic dysfunction syndrome are associated with cumulative metabolic burden beyond hyperglycaemia: a translational study.docx

In humans, the MetS with euglycaemia group exhibited peripheral neuropathy, with reduced nerve amplitudes and slowed NCV (P < 0.05). HRV analysis revealed significant cardiac autonomic dysfunction in the MetS with euglycaemia group, including reductions in the root mean square of successive differences (RMSSD), the standard deviation of normal-to-normal intervals (SDNN), total power (TP), high-frequency (HF) power, and the Poincaré long-axis index (SD2) (all P < 0.05)—deficits that were comparable to or exceeded those in the isolated hyperglycaemia group.

Gastrointestinal dysautonomia, however, was prominent only in the MetS with hyperglycaemia subgroup.</p>Interpretation<p>Both peripheral and autonomic neuropathies in MetS are associated with cumulative metabolic burden rather than hyperglycaemia alone, with organ-specific susceptibility patterns. These findings challenge a purely glucocentric view of MetS-related neural injury and support comprehensive risk-factor management in all MetS patients, irrespective of glycaemic status.</p>