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Association between diabetes and amyotrophic lateral sclerosis in S weden

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Mariosa, D., Kamel, F., Bellocco, R., Ye, W., Fang, F.·2015·European Journal of Neurology

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.

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  • Misclassification of some type 1 diabetes cases as type 2 would most likely have underestimated the real inverse association between type 2 diabetes and ALS risk.

    “Considering that diabetes mellitus type 1 has been shown to have a positive association with the risk of ALS, we expect that the misclassification of some cases of diabetes mellitus type 1 as type 2 would most likely have underestimated the real inverse association between diabetes type 2 and risk of ALS [38, 41].”

    From Lifestyle and medical conditions in relation to ALS risk and progression—an introduction to the Swedish ALSrisc Study (2024) · cites this paper as [38]

    The Discussion reports an inverse association for non-insulin-dependent diabetes and a positive association for insulin-dependent diabetes before age 50, while cautioning that insulin dependence does not cleanly distinguish type 1 from type 2. It does not say that type 1 cases were misclassified as type 2 or that such misclassification underestimated the inverse association. The paper's discussion of misclassification concerns diabetes ascertainment more generally. (LLM, conf=0.83)

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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 [38]

    The Discussion reports an inverse association between premorbid diabetes and ALS, mainly for non-insulin-dependent diabetes. But it says the inverse association was observed at age 70 and above, and the Conclusions describe an association rather than an established protective effect. The claim omits those qualifications. (LLM, conf=0.86)

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  • Diabetes mellitus type 1 has been shown to have a positive association with the risk of ALS.

    “Considering that diabetes mellitus type 1 has been shown to have a positive association with the risk of ALS, we expect that the misclassification of some cases of diabetes mellitus type 1 as type 2 would most likely have underestimated the real inverse association between diabetes type 2 and risk of ALS [38, 41].”

    From Lifestyle and medical conditions in relation to ALS risk and progression—an introduction to the Swedish ALSrisc Study (2024) · cites this paper as [38]

    The Discussion reports a positive association for insulin-dependent diabetes before age 50 and says early-onset diabetes appeared to be an ALS risk factor. But it also says the insulin-dependent group likely included both type 1 and type 2 diabetes; the Results report no positive association for insulin-dependent diabetes overall. The source therefore does not establish the unqualified claim for type 1 diabetes specifically. (LLM, conf=0.88)

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Research works printed but not linked: 24

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Authors
Mariosa, D., Kamel, F., Bellocco, R., Ye, W., & Fang, F.
Affiliations
  • Karolinska Institutet (SE)
  • National Institutes of Health (US)
Corresponding author
Mariosa, D.
Venue
European Journal of Neurology
Publisher
Wiley
Published
2015-01-19
Volume
22
Issue
11
Pages
1436-1442
ISSN
  • 1351-5101 (ISSN-L)
  • 1468-1331
OpenAlex
W2058662184
Cited by
120
References
1
Citations by year
2026: 4 · 2025: 7 · 2024: 7 · 2023: 11 · 2022: 13 · 2021: 21 · 2020: 14 · 2019: 10 · 2018: 8 · 2017: 10 · 2016: 9 · 2015: 5
FWCI
7.52
Type
journal article
Language
en
Open access
Locations
  • European Journal of Neurology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • BOA (University of Milano-Bicocca) (submittedVersion)
Funders
  • Swedish Research Council
  • Swedish Society for Medical Research
  • Swedish Research Council for Health
  • Swedish Research Council for Health, Working Life and Welfare
  • Karolinska Institutet Partial Finance
  • Intramural Research Program of the NIH (Z01 ES 049005)
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, type 1 diabetes, type 2 diabetes, ALS risk, energy metabolism, diabetes duration, age-specific associations, body mass index
MeSH terms
Adult, Aged, Aged, 80 and over, Amyotrophic Lateral Sclerosis, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Female, Humans, Male, Middle Aged, Registries, Sweden, Comorbidity, Case-Control Studies

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