Diabetes Mellitus, Obesity, and Diagnosis of Amyotrophic Lateral Sclerosis: A Population-Based Study
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IMPORTANCE: Although prior studies have suggested a role of cardiometabolic health on pathogenesis of amyotrophic lateral sclerosis (ALS), the association with diabetes mellitus has not been widely examined. Amyotrophic lateral sclerosis is the most common motor neuron disorder. Several vascular risk factors have been associated with decreased risk for ALS. Although diabetes is also a risk factor for vascular disease, the few studies of diabetes and ALS have been inconsistent. OBJECTIVE: To examine the association between diabetes and obesity, each identified through International Statistical Classification of Diseases, Eighth or Tenth Revision codes in a hospital registry, and ALS using data from the Danish National Registers. DESIGN, SETTING, AND PARTICIPANTS: Population-based nested case-control study of 3650 Danish residents diagnosed as having ALS between January 1, 1982, and December 31, 2009, and 365,000 controls (100 for each ALS case) matched on age and sex. The analysis was conducted in September and October 2014. MAIN OUTCOMES AND MEASURES: Adjusted odds ratio for ALS associated with diabetes or obesity diagnoses at least 3 years prior to the ALS diagnosis date. RESULTS: When considering diabetes and our obesity indicator together, the estimated odds ratio for ALS was 0.61 (95% CI, 0.46-0.80) for diabetes and 0.81 (95% CI, 0.57-1.16) for obesity. We observed no effect modification on the association with diabetes by sex. We did find a significant modification by age at ALS diagnosis and age at first mention of diabetes in the hospital registers. The protective association was stronger with increasing age at ALS diagnosis (P = .01), and the odds ratio for first mention of diabetes was 1.66 (95% CI, 0.85-3.21) before age 40 years but 0.52 (95% CI, 0.39-0.70) for older ages. These results are consistent with different associations for type 1 vs type 2 diabetes. CONCLUSIONS AND RELEVANCE: In this Danish nationwide study to investigate the association between diabetes and ALS diagnosis, our findings are in agreement with previous reports of a protective association between vascular risk factors and ALS and suggest that type 2 diabetes, but not type 1, is protective for ALS.
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Previous research shows a protective role of type 2 diabetes in the risk of ALS.
“We found an inverse association between a history of diabetes mellitus and ALS risk, which is in line with previous research showing a protective role of type 2 diabetes in the risk of ALS [38–40].”
From Lifestyle and medical conditions in relation to ALS risk and progression—an introduction to the Swedish ALSrisc Study (2024) · cites this paper as [39]
The Discussion reports a protective association between diabetes and ALS, but says the results only suggest that it applies to type 2 diabetes. The paper did not determine diabetes type with certainty, so the claim states the type 2 finding more firmly than the source does. (LLM, conf=0.82)
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- Authors
- Kioumourtzoglou, M.-A., Rotem, R. S., Seals, R. M., Gredal, O., Hansen, J., & Weisskopf, M. G.
- Affiliations
- Harvard University (US)
- National Rehabilitation Center for Neuromuscular Disorders, Copenhagen, Denmark
- Danish Cancer Society (DK)
- Corresponding author
- Kioumourtzoglou, Marianthi-Anna
- Venue
- JAMA Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2015-08-01
- Volume
- 72
- Issue
- 8
- Pages
- 905
- ISSN
- 2168-6149 (ISSN-L)
- PMC
- PMC4975611
- OpenAlex
- W1585186077
- Cited by
- 145
- References
- 60
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 14 · 2023: 15 · 2022: 8 · 2021: 21 · 2020: 21 · 2019: 15 · 2018: 12 · 2017: 17 · 2016: 10 · 2015: 1
- FWCI
- 9.40
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Environmental Health Sciences (P30ES000002, R01ES019188, T32ES007069)
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Amyloidosis: Diagnosis, Treatment, Outcomes
- Keywords
- amyotrophic lateral sclerosis, diabetes mellitus, obesity, type 2 diabetes, type 1 diabetes, cardiometabolic risk factors, vascular risk factors, motor neuron disease, age at diagnosis, sex differences
- MeSH terms
- Adult, Aged, Aged, 80 and over, Amyotrophic Lateral Sclerosis, Denmark, Diabetes Mellitus, Type 2, Female, Humans, Male, Middle Aged, Obesity, Registries, Risk Factors, Incidence, Case-Control Studies, Protective Factors
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