Diabetes May Provide Protection Against ALS, Study Suggests

The presence of diabetes is associated with a 70 percent reduction in the risk of amyotrophic lateral sclerosis (ALS), new study shows.

The study, titled “The role of pre-morbid diabetes on developing Amyotrophic Lateral Sclerosis,” was published in the European Journal of Neurology.

ALS patients tend to exhibit altered glucose metabolism; their cells are highly hypermetabolic (increased metabolism) and exhibit high energy consumption.

Multiple studies have investigated and discovered links between diabetes and ALS, but the results are controversial and varied. Some studies have found an increase in the prevalence of diabetes in ALS patients. However, several other studies have found that diabetes has a protective effect on the development of ALS.

However, no studies have looked at the relationship between the phenotype of ALS onset (bulbar or spinal) and the development or presence of diabetes.

So, researchers in Turin, Italy, set out to conduct a longitudinal study of a large Italian cohort to determine the relationship between diabetes and the development of ALS.

The group of patients included all 727,977 residents of Turin who were older than 14 years at the beginning of 1996.

Participants were followed-up for diagnosis of ALS between 1998 and 2014 using the Piedmont and Valle d’Aosta ALS Registry (PARALS). Diabetic patients in the group were determined using two regional sources — the Diabetes Registry and the ATC Drugs Prescriptions Archive.

Of the residents in Turin, 76,279 had diabetes and 397 patients developed ALS. The mean age at diagnosis for diabetes was 61, while the mean age for ALS onset was 67.5.

Among those with ALS, 24 already had Type 2 diabetes prior to ALS onset. Interestingly, the mean age of ALS onset in these patients (70.4 years) was three years higher than the non-diabetic patients (67.3 years), indicating a protective effect. However, this three-year delay in ALS development was not statistically significant due to the low number of cases.

Furthermore, researchers showed that developing diabetes led to a 70 percent lower chance of developing ALS. This result was statistically significant even after adjusting from gender and age, and after classifying the data by ALS phenotype (bulbar or spinal).

While the mechanism through which diabetes protects patients against ALS has not been explored, the authors offer two main hypotheses that could explain this phenomenon.

First, the high levels of glucose that are present in diabetic patients could help ALS patients compensate for their hypermetabolism, which may reduce the damage that regular ALS patients would experience to their motor neuron system due to the hypermetabolic state.

Second, this may occur due to high concentrations of progranulin, which is a molecule that is increased in diabetic patients and has been shown in animal models to revert damage to neurons.

“Our cohort study on a large urban area revealed a strong protective association between pre-morbid diabetes and ALS development, which concerned exclusively Type 2 diabetes and was not modified by age or gender,” the team concluded. “No relevant differences were found stratifying the analysis by bulbar and spinal ALS onset.”