Association between metabolic syndrome, its individual components and progression of amyotrophic lateral sclerosis

Metabolic abnormalities play a pivotal role in the pathogenesis of amyotrophic lateral sclerosis (ALS). Metabolic syndrome (MetS), a cluster of metabolic disorders, is highly prevalent among the elderly. However, the association between MetS and clinical characteristics, disease progression, and survival in ALS remains unclear.

We included 529 ALS patients and collected demographic, clinical, and hematological data, including blood glucose, HbA1c, and lipid profiles. Patients were followed longitudinally. MetS was defined according to the criteria of the Chinese Diabetes Society. Multivariate logistic regression, Kaplan-Meier survival analysis, and Cox proportional hazards models were used to analyze.

Compared to ALS patients without MetS, those with MetS had higher proportion of lower limb onset (44.3% vs. 24.6%, P < 0.001), and a faster disease progression rate (0.60 vs. 0.55, P = 0.022). After adjusting for confounders, MetS and hypertension were significantly associated with fast disease progression (OR = 1.808, 95% CI: 1.048-3.120, P = 0.033; OR = 2.615, 95% CI: 1.358-5.035, P = 0.004), and remained significant after multiple correction. Interaction analysis revealed significant interactions between glucose intolerance and dyslipidemia (P = 0.038), and between glucose intolerance and BMI (P = 0.040), but lost significance after multiple correction. There was no significant difference in survival between ALS patients with and without MetS. After adjusting for confounders, there was no significant association between MetS and the risk of death.

MetS, particularly in the presence of hypertension, was associated with fast disease progression in ALS, though not with survival. These suggest metabolic dysfunction may influence ALS progression and warrant further investigation.