Association between diabetes and amyotrophic lateral sclerosis in S weden
Open accessAbstract
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)
Experimental — accuracy not yet measuredPrevious 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)
Experimental — accuracy not yet measuredDiabetes 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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Cites
Autoimmune disease preceding amyotrophic lateral sclerosis: An epidemiologic study
Turner, M. R., Goldacre, R., Ramagopalan, S., Talbot, K., & Goldacre, M. J. (2013) · Neurology · doi:10.1212/wnl.0b013e3182a6cc13 · Cited by 185 · see citing works
Flagged first, then by citations
Research works printed but not linked: 24
- [1]Fang F Valdimarsdottir U Bellocco R Amyotrophic lateral sclerosis in Sweden, 1991–2005 Archives of neurology 2009 66 4 515 9 19364937
- [2]Trojsi F Monsurro MR Tedeschi G Exposure to environmental toxicants and pathogenesis of amyotrophic lateral sclerosis: state of the art and research perspectives International journal of molecular sciences 2013 14 8 15286 311 23887652 PMC3759860
- [3]Turner MR Hardiman O Benatar M Controversies and priorities in amyotrophic lateral sclerosis Lancet neurology 2013 12 3 310 22 23415570 PMC4565161
- [4]Korner S Kollewe K Ilsemann J Prevalence and prognostic impact of comorbidities in amyotrophic lateral sclerosis European journal of neurology: the official journal of the European Federation of Neurological Societies 2013 20 4 647 54 23094606
- [5]Kalkonde YV Jawaid A Qureshi SU Medical and environmental risk factors associated with frontotemporal dementia: a case-control study in a veteran population Alzheimer’s & dementia: the journal of the Alzheimer’s Association 2012 8 3 204 10 22465176
- [6]Desport JC Preux PM Magy L Factors correlated with hypermetabolism in patients with amyotrophic lateral sclerosis The American journal of clinical nutrition 2001 74 3 328 34 11522556
- [7]Pradat PF Bruneteau G Gordon PH Impaired glucose tolerance in patients with amyotrophic lateral sclerosis Amyotrophic lateral sclerosis: official publication of the World Federation of Neurology Research Group on Motor Neuron Diseases 2010 11 1–2 166 71 20184518
- [8]Jawaid A Salamone AR Strutt AM ALS disease onset may occur later in patients with pre-morbid diabetes mellitus European journal of neurology: the official journal of the European Federation of Neurological Societies 2010 17 5 733 9 20074230
- [10]Seelen M van Doormaal PT Visser AE Prior medical conditions and the risk of amyotrophic lateral sclerosis Journal of neurology 2014 25059395
- [11]Lekoubou A Matsha TE Sobngwi E Effects of diabetes mellitus on amyotrophic lateral sclerosis: a systematic review BMC research notes 2014 7 171 24661645 PMC3987838
- [12]Ludvigsson JF Otterblad-Olausson P Pettersson BU The Swedish personal identity number: possibilities and pitfalls in healthcare and medical research European journal of epidemiology 2009 24 11 659 67 19504049 PMC2773709
- [13]Pisa FE Verriello L Deroma L The accuracy of discharge diagnosis coding for Amyotrophic Lateral Sclerosis in a large teaching hospital European journal of epidemiology 2009 24 10 635 40 19657715
- [14]Miller RG Secrest AM Sharma RK Improvements in the life expectancy of type 1 diabetes: the Pittsburgh Epidemiology of Diabetes Complications study cohort Diabetes 2012 61 11 2987 92 22851572 PMC3478551
- [15]Stallings NR Puttaparthi K Dowling KJ TDP-43, an ALS linked protein, regulates fat deposition and glucose homeostasis PloS one 2013 8 8 e71793 23967244 PMC3742534
- [16]Laird AS Van Hoecke A De Muynck L Progranulin is neurotrophic in vivo and protects against a mutant TDP-43 induced axonopathy PloS one 2010 5 10 e13368 20967127 PMC2954192
- [17]Qu H Deng H Hu Z Plasma progranulin concentrations are increased in patients with type 2 diabetes and obesity and correlated with insulin resistance Mediators of inflammation 2013 2013 360190 23476101 PMC3588183
- [18]Kahn SE Hull RL Utzschneider KM Mechanisms linking obesity to insulin resistance and type 2 diabetes Nature 2006 444 7121 840 6 17167471
- [19]O’Reilly EJ Wang H Weisskopf MG Premorbid body mass index and risk of amyotrophic lateral sclerosis Amyotrophic lateral sclerosis & frontotemporal degeneration 2013 14 3 205 11 23134505 PMC3615420
- [20]Cohen E Dillin A The insulin paradox: aging, proteotoxicity and neurodegeneration Nature reviews Neuroscience 2008 9 10 759 67 18769445 PMC2692886
- [21]Raj SM Howson JM Walker NM No association of multiple type 2 diabetes loci with type 1 diabetes Diabetologia 2009 52 10 2109 16 19455305 PMC2738846
- [22]Kaneb HM Sharp PS Rahmani-Kondori N Metformin treatment has no beneficial effect in a dose-response survival study in the SOD1(G93A) mouse model of ALS and is harmful in female mice PloS one 2011 6 9 e24189 21909419 PMC3164704
- [23]Dupuis L Dengler R Heneka MT A randomized, double blind, placebo-controlled trial of pioglitazone in combination with riluzole in amyotrophic lateral sclerosis PloS one 2012 7 6 e37885 22715372 PMC3371007
- [24]Dupuis L Corcia P Fergani A Dyslipidemia is a protective factor in amyotrophic lateral sclerosis Neurology 2008 70 13 1004 9 18199832
- [25]Ludvigsson JF Andersson E Ekbom A External review and validation of the Swedish national inpatient register BMC public health 2011 11 450 21658213 PMC3142234
Cited by
Sorted by citations
Li, Y., Peng, Y., Shen, Y., Zhang, Y., Liu, L., & Yang, X. (2023) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2022.2076064 · Cited by 156 · see citing works
Diabetes Mellitus, Obesity, and Diagnosis of Amyotrophic Lateral Sclerosis: A Population-Based Study
Kioumourtzoglou, M.-A., Rotem, R. S., Seals, R. M., Gredal, O., Hansen, J., & Weisskopf, M. G. (2015) · JAMA Neurology · doi:10.1001/jamaneurol.2015.0910 · Cited by 145 · see citing works
Genome-wide genetic links between amyotrophic lateral sclerosis and autoimmune diseases
Li, C. Y., Yang, T. M., Ou, R. W., Wei, Q. Q., & Shang, H. F. (2021) · BMC Medicine · doi:10.1186/s12916-021-01903-y · Cited by 48 · see citing works
Gut microbiome and amyotrophic lateral sclerosis: a systematic review of current evidence
Sun, J., Huang, T., Debelius, J. W., & Fang, F. (2021) · Journal of Internal Medicine · doi:10.1111/joim.13336 · Cited by 43 · see citing works
Self-citationChourpiliadis, C., Seitz, C., Lovik, A., Joyce, E. E., Pan, L., Hu, Y., Kläppe, U., Samuelsson, K., Press, R., Ingre, C., et al. (2024) · Journal of Neurology · doi:10.1007/s00415-024-12496-w · Cited by 10 · see citing works
“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].”
BackgroundResultSelf-citation
- 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
- PMC
- PMC4506907
- 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
- green
- www.ncbi.nlm.nih.gov
- 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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