Does type 2 diabetes protect against Lou Gehrig’s?

People with type 2 diabetes - but not obesity - may have a lower risk for being diagnosed with amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, according to a study published June 1, 2015 online in JAMA Neurology.

Researchers at Harvard T.H. Chan School of Public Health conducted a nationwide epidemiologic study using data from Denmark and observed a protective association between diabetes and diagnosis for ALS.

Lead author Marianthi-Anna Kioumourtzoglou, research fellow in the Department of Environmental Health at Harvard T.H. Chan School and colleagues, conducted a population-based case-control study nested in the entire Danish population. They identified 3,650 ALS cases between 1982 and 2009 and matched each case to 100 controls on age, sex and vital status. ICD-8 (before 1994) and ICD-10 codes (after that) were used to identify ALS cases and ascertain diabetes status. The researchers also considered information on marital status, residence region, socio-economic status (based on job title), and chronic obstructive pulmonary disease diagnoses (as a surrogate for tobacco smoking). They then ran conditional logistic regressions with strata defined by the 1:100 case-control sets to examine the association between diabetes and ALS diagnoses. Sensitivity analyses were conducted to investigate whether age at first ALS or first diabetes diagnosis, or sex, modify the observed associations.

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"Because the etiology for ALS is not completely understood, identification of risk -or protective - factors is very important," Kioumourtzoglou tells Medical Economics. "Our observed association between diabetes and ALS provides some additional information to our understanding about ALS. Of course our results should be replicated -as is always the case with epidemiologic studies - but we believe our paper could be the start of a discussion and focus further attention on the role of energy metabolism in ALS pathogenesis."

Although the researchers were not able to directly separate type 1 vs 2 diabetes through the ICD codes, as these are usually misclassified (e.g. about 75% of participants with a type 1 diagnosis also had a type 2 diagnosis), conducting sensitivity analyses looking at whether age at first ALS diagnosis or first diabetes diagnosis suggested that the protective association is likely with type 2 diabetes, while type 1 diabetes might be a risk factor (although this latter finding was not statistically significant). For example, the researchers observed an odds ratio of 0.52 (95% Confidence Interval: 0.39-0.70) for first diabetes-related diagnosis above aged 40 years (i.e. likely type 2), and 1.66 (95%CI: 0.85-3.21) for first diabetes-related diagnosis below aged 40 years.

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"Our findings provide some additional support on the idea that energy metabolism plays an important role in ALS pathogenesis," says Kioumourtzoglou. "The specific underlying mechanisms for our observed association between diabetes and ALS are currently unknown, therefore the immediate clinical implications are not necessarily clear.

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"We would definitely not advertise that people should get diabetes to protect themselves from ALS, as diabetes is a known risk factor for many other outcomes, such as cardiovascular diseases," she adds. "What exact aspect of diabetes is responsible for the observed protective association needs to be first identified and that information could then potentially help develop some preventive guidelines in the future."

The researchers were able to conduct a nationwide study, and thus identify a very large number of ALS cases.

"Because ALS is a rare disease, very large-scale epidemiologic studies, usually uncommon, are very important for identification of factors contributing in ALS pathophysiology. In addition, we were able to, even quite indirectly, examine the association with type 1 and type 2 diabetes, and our results suggested likely different association with ALS by diabetes type," Kioumourtzoglou says.