Association between diabetes and amyotrophic lateral sclerosis in Sweden

Abstract

Background and purpose: Energy metabolism is altered in patients with amyotrophic lateral sclerosis (ALS) but the role of diabetes is largely unknown.

Methods: A population-based case-control study was conducted of 5108 ALS cases and 25,540 individually matched population controls during 1991-2010. Information on ALS and pre-existing diabetes was retrieved from the Swedish Patient Register to explore the association of ALS with diabetes overall and with insulin-dependent or non-insulin-dependent diabetes specifically. Variation of the association by diabetes duration and age was also studied.

Results: In total, 224 ALS cases (4.39%) and 1437 controls (5.63%) had diabetes before the index date, leading to an overall inverse association between diabetes and ALS risk [odds ratio (OR) 0.79, 95% confidence interval (CI) 0.68-0.91]. The association was strong for non-insulin-dependent diabetes (OR 0.66, 95% CI 0.53-0.81) but not for insulin-dependent diabetes (OR 0.83, 95% CI 0.60-1.15) and varied as a function of diabetes duration, with the strongest association observed around 6 years after first ascertainment of diabetes. The association was age-specific; the inverse association was noted only amongst individuals aged 70 or older. In contrast, for younger individuals (<50 years), pre-existing insulin-dependent diabetes was associated with a higher ALS risk (OR 5.38, 95% CI 1.87-15.51).

Conclusions: Our study suggests that there is an association between diabetes and ALS, and highlights the importance of taking into account age, insulin dependence and diabetes duration. Future studies should explore whether the association is independent of body mass index.

Keywords: amyotrophic lateral sclerosis; diabetes; epidemiology; insulin dependence; metabolic and endocrine disorders; motor neuron disease; neurological disorders; neuromuscular diseases; research methods.

Figure 1

Observed distribution of the adjusted odds ratio (OR) of ALS for diabetes.

Figure 2

Temporal relationship between diabetes duration and ALS. (A) Main analysis where diabetes was ascertained from 1987 onward. (B) Sensitivity analyses where diabetes was ascertained from 1964 onward. (C) Sensitivity analyses where diabetes was ascertained from 1964 onward and excluding the individuals with diabetes before age 30.