Risk of amyotrophic lateral sclerosis in patients with diabetes: A nationwide population-based cohort study

Background: Glucose intolerance in patients with amyotrophic lateral sclerosis (ALS) has been inconsistently reported. Evidence for the association of ALS and diabetes mellitus is limited. We aimed to assess the overall and age- and sex-specific risks of ALS among patients with diabetes in Taiwan. Methods: The study cohort included 615 492 diabetic patients and 614 835 age- and sex-matched subjects as a comparison cohort, followed from 2000 to 2008. We estimated the incidence densities of ALS and calculated the relative hazard ratios (HRs) of ALS (ICD-9-CM 335.20) in relation to diabetes using a Cox proportional hazard regression model, with adjustment for potential confounders, including sex, age, geographic area, urbanization status, Charlson Comorbidity Index, frequency of medical visit, and histories of hypertension, hyperlipidemia, and chronic obstructive pulmonary disease. Results: Over a 9-year period, 255 diabetic and 201 non-diabetic subjects developed ALS, corresponding to incidence densities of 7.42 and 5.06 per 100 000 person-years, respectively. After adjustment for potential confounders, patients with diabetes experienced a significantly elevated HR of 1.35 (95% confidence interval [CI], 1.10-1.67). A higher covariate adjusted HR was noted in men (HR 1.48; 95% CI, 1.13-1.94) than in women (HR 1.17; 95% CI, 0.84-1.64), while men aged ≤65 years showed the most increased HR of 1.67 (95% CI, 1.18-2.36). Conclusions: This study demonstrated a moderate but significant association of diabetes with ALS onset, and such association is not confounded by socio-demographic characteristics or certain ALS-related co-morbidities. Further studies are warranted to examine whether the findings observed in our study can be replicated.