Alterations in metabolic biomarkers and their potential role in amyotrophic lateral sclerosis

Background: Metabolic dysfunction has been suggested to be involved in the pathophysiology of amyotrophic lateral sclerosis (ALS). This study aimed to investigate the potential role of metabolic biomarkers in the progression of ALS and understand the possible metabolic mechanisms. Methods: Fifty-two patients with ALS and 24 normal controls were included, and blood samples were collected for analysis of metabolic biomarkers. Basal anthropometric measures, including body composition and clinical features, were measured in ALS patients. The disease progression rate was calculated using the revised ALS functional rating scale (ALSFRS-R) during the 6-month follow-up. Results: ALS patients had higher levels of adipokines (adiponectin, adipsin, resistin, and visfatin) and other metabolic biomarkers [C-peptide, glucagon, glucagon-like peptide 1 (GLP-1), gastric inhibitory peptide, and plasminogen activator inhibitor type 1] than controls. Leptin levels in serum were positively correlated with body mass index, body fat, and visceral fat index (VFI). Adiponectin was positively correlated with the VFI and showed a positive correlation with the ALSFRS-R and a negative correlation with baseline disease progression. Patients with lower body fat, VFI, and fat in limbs showed faster disease progression during follow-ups. Lower leptin and adiponectin levels were correlated with faster disease progression. After adjusting for confounders, lower adiponectin levels and higher visfatin levels were independently correlated with faster disease progression. Interpretation: The current study found altered levels of metabolic biomarkers in ALS patients, which may play a role in ALS pathogenesis. Adiponectin and visfatin represent potential biomarkers for prediction of disease progression in ALS.