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oai:figshare.com:article/34008048 2026-09-28T04:27:15Z category_658 portal_316 item_type_3 month_year_09_2026

Supplementary file 2_Neurological manifestations in metabolic dysfunction syndrome are associated with cumulative metabolic burden beyond hyperglycaemia: a translational study.docx Jinfang Ma (38894) Yi Tang (55726) Qingxing Xie (18283785) Shishi Xu (3349544) Sumin Shen (6858611) Yuwei Zhang (388956) Fang Zhang (197215) Jing Li (10611) Hui Jiang (102809) Xiaodan Zhong (6021560) Nanwei Tong (3349547) Cell Metabolism autonomic dysfunction hyperglycaemia metabolic syndrome neuropathy peripheral nerve damage Objective<p>To determine whether neurological injury in metabolic syndrome (MetS) extends beyond hyperglycaemia-driven neuropathy.</p>Methods<p>We employed a translational design combining controlled rat models of isolated and combined MetS components with a community-based cross-sectional human study. Preclinically, ten rat models (n = 6 per group) representing various MetS phenotypes were assessed for metabolic parameters and peripheral neurological function. Clinically, 1,176 adults were stratified by glycaemic and MetS status according to International Diabetes Federation (IDF) criteria. Participants underwent anthropometric measurements, fasting biochemistry, peripheral nerve function assessment by electromyography (EMG), and autonomic function evaluation by heart rate variability (HRV) and electrogastrography (EGG).</p>Results<p>In animal models, hindpaw withdrawal latencies were prolonged and nerve conduction velocity (NCV) was significantly reduced across multiple MetS phenotypes, irrespective of glycaemic status. 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> 2026-09-28T04:27:15Z Dataset Dataset 10.3389/fendo.2026.1946996.s001 https://figshare.com/articles/dataset/Supplementary_file_2_Neurological_manifestations_in_metabolic_dysfunction_syndrome_are_associated_with_cumulative_metabolic_burden_beyond_hyperglycaemia_a_translational_study_docx/34008048 CC BY 4.0