Risk of Amyotrophic Lateral Sclerosis in Patients With Diabetes: A Nationwide Population-Based Cohort Study

Abstract

BackgroundGlucose 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.MethodsThe 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.ResultsOver 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).ConclusionsThis 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.

Response to the letter ‘Type 2 diabetes and amyotrophic lateral sclerosis’

“…The statistically significant increase in the risk of ALS before age 50 amongst individuals with insulin-dependent diabetes was based on eight cases and seven controls with insulin-dependent diabetes. However, in the study by Sun et al [4] men aged ≤65 years showed the most increased hazard ratio (HR) of ALS for diabetes (1.67, 95% CI 1.18-2.36), consistent with the HR of ALS before age 65 amongst men in our study (1.70, 95% CI 0.98-2.96, 17 cases and 50 controls with diabetes). The literature suggests that young-onset diabetes may be associated with increased ALS risk and further research on the role of type 1 diabetes in ALS is warranted.…”

Altered Metabolic Homeostasis in Amyotrophic Lateral Sclerosis: Mechanisms of Energy Imbalance and Contribution to Disease Progression

“…However, the incidence of abnormal glucose tolerance tests in ALS patients ranges from 19-72% [9,113,115,116,117,118], and therefore subtle alterations in glucose handling could occur in ALS. Abnormal glucose metabolism does not appear to affect survival or disease severity [114,119]; however, one Taiwanese study reported an increased risk of ALS in those with DM [120]. By contrast, a Danish study found that type 2 DM is protective for ALS [121], and individuals with DM have been found to have an average of 4 years later onset of ALS than those without DM [122].…”

Incretin-based therapy for type 2 diabetes mellitus is promising for treating neurodegenerative diseases

“…A recent systematic review also revealed that ALS was associated with diabetes mellitus (Lekoubou et al, 2014). However, whether there is a causal relationship between glucose homeostasis abnormalities and ALS is controversial (Sun et al, 2015). Moreover, two antidiabetic drugs, metformin and pioglitazone, seem to have no beneficial effect in the SOD1 G93A mouse model of ALS (Kaneb et al, 2011) and a clinical trial (Dupuis et al, 2012;Jawaid et al, 2014).…”