Exploring the Role of Diabetes in ALS: A Population-Based Cohort Study

Area of Science:

• Neurology
• Endocrinology
• Genetics

Background:

• Type 2 diabetes mellitus (T2DM) is a common comorbidity in amyotrophic lateral sclerosis (ALS).
• The impact of T2DM on ALS progression and clinical presentation requires further investigation.

Purpose of the Study:

• To investigate the prevalence and clinical characteristics of T2DM in a large ALS cohort.
• To explore the association between T2DM and disease severity, respiratory function, and genetic factors in ALS patients.

Main Methods:

• Retrospective cohort study utilizing data from the ALS registry of Emilia Romagna, Italy (2009-2021).
• Analysis of 1756 ALS patients, comparing those with T2DM (diALS) to those without (ndALS).
• Assessment of clinical parameters, respiratory function (Forced Vital Capacity, Non-Invasive Ventilation use), and genetic testing (C9ORF72).

Main Results:

• T2DM patients (diALS) were older, had higher BMI, and experienced greater weight loss at diagnosis compared to ndALS.
• diALS showed a higher frequency of respiratory onset and phenotype, lower Forced Vital Capacity, and increased Non-Invasive Ventilation use.
• The C9ORF72 gene expansion was significantly underrepresented in the diALS group (0% vs. 7.64% in ndALS).

Conclusions:

• T2DM in ALS is associated with more severe respiratory dysfunction, potentially indicating specific respiratory muscle frailty.
• Clinical features in diALS are consistent with literature, including later onset.
• The reduced prevalence of C9ORF72 expansion in diALS suggests a potential role in metabolism and inflammation, warranting further research into non-genetic factors.