Riassunto analitico
BACKGROUND AND AIMS Amyotrophic lateral sclerosis (ALS) is a disabling neurodegenerative disease characterized by significant pathogenic and clinical heterogeneity. Metabolic diseases, particularly diabetes mellitus (DM), have been variously linked to ALS, but the evidence has been inconsistent and often conflicting. If on one hand, some studies report an increased risk of ALS with diabetes, other report an increase if DM is diagnosed at a younger age, and a reduction when diagnosed at an older age. DM does not seem to affect the prognosis of ALS, which may weaken the potential causal link between the two diseases. In this study, we aimed at characterizing clinical features and prognosis of patients affected by both ALS and DM (diALS).
METHODS ALS patients prospectively registered within the ALS registry of Emilia Romagna since 2009 were included in the study. Among these patients, those also affected by DM were characterized and compared to those without DM (ndALS). Disease progression, prognostic factors, and survival were examined.
RESULTS Out of a study cohort of 1756 ALS patients,145 were also affected by DM. Patients with diALS were older than those with ndALS (mean age at onset 71.56 vs 65.76, p<0.001), had a higher BMI (mean 25.63 vs 24.23, p<0.001), and experienced greater weight loss at diagnosis (mean 6.87 vs 5.44, p=0.07). Respiratory onset (% 6.2 vs 2.6, p=0.013) and respiratory phenotype (% 4.2 vs 1.4, p=0.04) were more frequent among diALS, while distal upper limb onset was more common in the ndALS group (% 16.5 vs 26.6, p=0.008). At diagnosis, diALS had a lower FVC value (mean 74.8 vs 87.9, p=<0.001), confirmed by regression analysis including age at onset and sex. Heart diseases (% 30.5 vs 15.5, p=<0.001) and COPD (% 12.4 vs 7.2, p=0.024) were more prevalent in diALS compared to ndALS, while NIV usage was observed in 50.35% of diALS compared to 37.61% of ndALS (p=0.003). The median survival of the general population was 43.81 months, with a non-statistically significant difference between diALS (35.89 months) and ndALS (44.43 months). There were no differences in the genetic background between the two groups, with the exception of C9ORF72, which was underrepresented among diALS (p=0.039).
CONCLUSIONS Diabetic patients with ALS showed some peculiar clinical features consistent with previous literature and presented with comorbidities expectedly associated with DM. They showed a higher and earlier prevalence of respiratory dysfunction, independent of age and sex, suggesting a negative impact on the disease, although DM did not seem to affect patients’ survival. The intriguing finding of a lower prevalence of C9ORF72 expansion in this population may hint towards a specific role of the gene in metabolism and inflammation, warranting further studies for confirmation.
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