People with diabetes mellitus, particularly those with type 2 diabetes, appear to be at a significantly lower risk of amyotrophic lateral sclerosis (ALS) than those without this metabolic disorder, a review study reported.
Its findings support previous research suggesting diabetes to be a protective factor against ALS, potentially due to the changes in glucose metabolism that mark this widespread disorder, its investigators wrote, noting additional research is needed.
While previous evidence has suggested that diabetes could protect against the development of ALS, study results have been inconsistent.
To clarify earlier findings, researchers at Case Western University Hospital and the Cleveland Clinic conducted a systematic review of studies, published through the start of this year, investigating ALS risk among people with and without diabetes.
From a total of 1,683 studies, they included 11 in their meta-analysis — an approach that combines the results of multiple scientific studies to increase the pool of data, allowing for a more comprehensive review.
Specifically, they included three cohort studies, which follow a population over time to determine who develops disease (ALS in this case), and eight case-control studies, which compares patients with and without ALS to determine differences between them (such as the proportion of patients with diabetes).
Results found diabetic patients were 32% less likely to develop ALS than those without diabetes — a significant risk reduction.
Notably, this risk appeared to be even lower (41%) in people with type 2 diabetes. However, the researchers warned that such results “must be interpreted with caution as only a few studies provided data on DM [diabetes] subtype.”
Three possible reasons were given for the lower incidence of ALS among diabetic patients. First, people with diabetes tend to produce more of a protein called progranulin, which appears to degrade the toxic protein clumps that mark ALS.
“[A] higher level of progranulin than the general population has been observed in patients with insulin resistance and type 2 DM,” the researchers wrote. “This high level of progranulin may, in turn, play a protective role against the development of ALS.”
Second, neurons in ALS patients are in a hypermetabolic state, meaning they demand considerable amounts of energy. High blood sugar levels due to diabetes may “serve as an unintentional compensatory mechanism” of this high energy demand, delaying ALS onset, they wrote.
Third, higher glucose levels may prevent the production of stress granules in response to energy deprivation, which are thought to participate in the deposition of protein clumps in ALS.
It is also possible, the researchers wrote, that diabetes is not the causative mechanism. Rather, they suggested that results of studies analyzed could be confounded by participants’ body mass index (BMI, a measure of body fat). A high BMI, or being overweight or obese, is a strong risk factor for diabetes, but correlates negatively with ALS.
Limitations to this work, the researchers noted, included data on confounding variables such as smoking, physical activity, and disease severity not being available in all studies analyzed.
Still, their report is the first comprehensive investigation of the relationship between diabetes and ALS.
“The current study found a lower risk of DM patients to develop ALS,” the researchers concluded. “However, the mechanisms behind this negative association remain unknown and further studies are still needed.”
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