Type II diabetes mellitus and the incidence of amyotrophic lateral sclerosis

Journal of Neurology volume 266, pages2233–2243(2019)Cite this article

Abstract

Objective

The aim of this study was to investigate the relationship between type II diabetes mellitus (T2DM) and ALS incidence using the National Health Insurance Research Database and Serious Disabling Disease database of Taiwan.

Methods

This was a population-based cohort study. The index date was the date of the first T2DM diagnosis + 365 days. We included T2DM patients diagnosis between 2000 and 2013 (n = 2,135,427). These patients were matched by sex, age, urbanization, and insurance premium at a ratio of 1:1 to include patients without diabetes mellitus. Competing risk-adjusted Cox regression analysis was performed to investigate the association between T2DM and the incidence of ALS.

Results

In the patients not stratified by age, T2DM was not associated with the incidence of ALS after controlling for confounding factors. The interaction test of age subgroup (< 55 and ≥ 55 years) and T2DM on ALS risk was significance (p < 0.001). Subgroup analysis showed that T2DM was negatively associated with ALS in patients whose age at the first T2DM diagnosis was ≥ 55 years. Among T2DM patients, T2DM combined with hypertension was negatively associated with ALS among patients whose age at the first T2DM diagnosis was ≥ 55 years. Among T2DM patients, T2DM combined with hyperlipidemia was positively associated with ALS among patients whose age at the first T2DM diagnosis was < 55 years.

Conclusions

The late-onset of T2DM may exert negative association with ALS, especially when combined with hypertension. The early-onset of T2DM may exert positive association with ALS, especially when combined with hyperlipidemia.

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References

  1. 1.

    Tsai CP, Wang KC, Hwang CS, Lee IT, Lee CT (2015) Incidence, prevalence, and medical expenditures of classical amyotrophic lateral sclerosis in Taiwan, 1999–2008. J Formos Med Assoc 114(7):612–619. https://doi.org/10.1016/j.jfma.2013.01.008

    Article  PubMed  Google Scholar 

  2. 2.

    Holecek V, Rokyta R (2018) Possible etiology and treatment of amyotrophic lateral sclerosis. Neuro Endocrinol Lett 38(8):528–531

    PubMed  Google Scholar 

  3. 3.

    Hollinger SK, Okosun IS, Mitchell CS (2016) Antecedent disease and amyotrophic lateral sclerosis: what is protecting whom? Front Neurol 7:47. https://doi.org/10.3389/fneur.2016.00047

    Article  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Dorst J, Kuhnlein P, Hendrich C, Kassubek J, Sperfeld AD, Ludolph AC (2011) Patients with elevated triglyceride and cholesterol serum levels have a prolonged survival in amyotrophic lateral sclerosis. J Neurol 258(4):613–617. https://doi.org/10.1007/s00415-010-5805-z

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    Jawaid A, Salamone AR, Strutt AM, Murthy SB, Wheaton M, McDowell EJ, Simpson E, Appel SH, York MK, Schulz PE (2010) ALS disease onset may occur later in patients with pre-morbid diabetes mellitus. Eur J Neurol 17(5):733–739. https://doi.org/10.1111/j.1468-1331.2009.02923.x

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Gallo V, Wark PA, Jenab M, Pearce N, Brayne C, Vermeulen R, Andersen PM, Hallmans G, Kyrozis A, Vanacore N, Vahdaninia M, Grote V, Kaaks R, Mattiello A, Bueno-de-Mesquita HB, Peeters PH, Travis RC, Petersson J, Hansson O, Arriola L, Jimenez-Martin JM, Tjonneland A, Halkjaer J, Agnoli C, Sacerdote C, Bonet C, Trichopoulou A, Gavrila D, Overvad K, Weiderpass E, Palli D, Quiros JR, Tumino R, Khaw KT, Wareham N, Barricante-Gurrea A, Fedirko V, Ferrari P, Clavel-Chapelon F, Boutron-Ruault MC, Boeing H, Vigl M, Middleton L, Riboli E, Vineis P (2013) Prediagnostic body fat and risk of death from amyotrophic lateral sclerosis: the EPIC cohort. Neurology 80(9):829–838. https://doi.org/10.1212/WNL.0b013e3182840689

    Article  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Ji J, Sundquist J, Sundquist K (2016) Association of alcohol use disorders with amyotrophic lateral sclerosis: a Swedish National Cohort Study. Eur J Neurol 23(2):270–275. https://doi.org/10.1111/ene.12667

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Jawaid A, Khan R, Polymenidou M, Schulz PE (2018) Disease-modifying effects of metabolic perturbations in ALS/FTLD. Mol Neurodegener 13(1):63. https://doi.org/10.1186/s13024-018-0294-0

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  9. 9.

    D'Ovidio F, d'Errico A, Carna P, Calvo A, Costa G, Chio A (2018) The role of pre-morbid diabetes on developing amyotrophic lateral sclerosis. Eur J Neurol 25(1):164–170. https://doi.org/10.1111/ene.13465

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Kioumourtzoglou MA, Rotem RS, Seals RM, Gredal O, Hansen J, Weisskopf MG (2015) Diabetes mellitus, obesity, and diagnosis of amyotrophic lateral sclerosis: a population-based study. JAMA Neurol 72(8):905–911. https://doi.org/10.1001/jamaneurol.2015.0910

    Article  PubMed  PubMed Central  Google Scholar 

  11. 11.

    Mariosa D, Kamel F, Bellocco R, Ye W, Fang F (2015) Association between diabetes and amyotrophic lateral sclerosis in Sweden. Eur J Neurol 22(11):1436–1442. https://doi.org/10.1111/ene.12632

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Turner MR, Goldacre R, Talbot K, Goldacre MJ (2016) Psychiatric disorders prior to amyotrophic lateral sclerosis. Ann Neurol 80(6):935–938. https://doi.org/10.1002/ana.24801

    Article  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Sutedja NA, van der Schouw YT, Fischer K, Sizoo EM, Huisman MH, Veldink JH, Van den Berg LH (2011) Beneficial vascular risk profile is associated with amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 82(6):638–642. https://doi.org/10.1136/jnnp.2010.236752

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Hardiman O (2011) Amyotrophic lateral sclerosis and vascular risk: a metabolic conundrum. J Neurol Neurosurg Psychiatry 82(6):591. https://doi.org/10.1136/jnnp.2011.241539

    Article  PubMed  Google Scholar 

  15. 15.

    Turner MR, Goldacre R, Talbot K, Goldacre MJ (2015) Cerebrovascular injury as a risk factor for amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 87(3):244–246. https://doi.org/10.1136/jnnp-2015-311157

    Article  PubMed  PubMed Central  Google Scholar 

  16. 16.

    Logroscino G, Ludolph A (2014) Amyotrophic lateral sclerosis: new ideas from cancer. Lancet Neurol 13(11):1067–1068. https://doi.org/10.1016/S1474-4422(14)70177-2

    Article  PubMed  Google Scholar 

  17. 17.

    Gibson SB, Abbott D, Farnham JM, Thai KK, McLean H, Figueroa KP, Bromberg MB, Pulst SM, Cannon-Albright L (2016) Population-based risks for cancer in patients with ALS. Neurology 87(3):289–294. https://doi.org/10.1212/WNL.0000000000002757

    Article  PubMed  PubMed Central  Google Scholar 

  18. 18.

    Turner MR, Goldacre R, Ramagopalan S, Talbot K, Goldacre MJ (2013) Autoimmune disease preceding amyotrophic lateral sclerosis: an epidemiologic study. Neurology 81(14):1222–1225

    CAS  Article  Google Scholar 

  19. 19.

    Paganoni S, Hyman T, Shui A, Allred P, Harms M, Liu J, Maragakis N, Schoenfeld D, Yu H, Atassi N (2015) Pre-morbid type 2 diabetes mellitus is not a prognostic factor in amyotrophic lateral sclerosis. Muscle Nerve 52(3):339–343

    Article  Google Scholar 

  20. 20.

    Sun Y, Lu CJ, Chen RC, Hou WH, Li CY (2015) Risk of amyotrophic lateral sclerosis in patients with diabetes: a nationwide population-based cohort study. J Epidemiol 25(6):445–451. https://doi.org/10.2188/jea.JE20140176

    Article  PubMed  PubMed Central  Google Scholar 

  21. 21.

    Freedman DM, Wu J, Daugherty SE, Kuncl RW, Enewold LR, Pfeiffer RM (2014) The risk of amyotrophic lateral sclerosis after cancer in US elderly adults: a population-based prospective study. Int J Cancer 135(7):1745–1750. https://doi.org/10.1002/ijc.28795

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  22. 22.

    National Health Research Institute (1998) Introduction to the national health insurance research database (NHIRD). Taiwan. http://nhird.nhri.org.tw/en/. Retrieved May 2019

  23. 23.

    Lin CC, Lai MS, Syu CY, Chang SC, Tseng FY (2005) Accuracy of diabetes diagnosis in health insurance claims data in Taiwan. J Formos Med Assoc 104(3):157–163

    PubMed  Google Scholar 

  24. 24.

    Vandoorne T, De Bock K, Van Den Bosch L (2018) Energy metabolism in ALS: an underappreciated opportunity? Acta Neuropathol 135(4):489–509. https://doi.org/10.1007/s00401-018-1835-x

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  25. 25.

    Dupuis L, Pradat PF, Ludolph AC, Loeffler JP (2011) Energy metabolism in amyotrophic lateral sclerosis. Lancet Neurol 10(1):75–82. https://doi.org/10.1016/s1474-4422(10)70224-6

    CAS  Article  Google Scholar 

  26. 26.

    Mitchell CS, Hollinger SK, Goswami SD, Polak MA, Lee RH, Glass JD (2015) Antecedent disease is less prevalent in amyotrophic lateral sclerosis. Neurodegener Dis 15(2):109–113. https://doi.org/10.1159/000369812

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  27. 27.

    Kaur P, Muthuraman A, Kaur M (2015) The implications of angiotensin-converting enzymes and their modulators in neurodegenerative disorders: current and future perspectives. ACS Chem Neurosci 6(4):508–521. https://doi.org/10.1021/cn500363g

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Lin FC, Tsai CP, Kuang-Wu Lee J, Wu MT, Tzu-Chi Lee C (2015) Angiotensin-converting enzyme inhibitors and amyotrophic lateral sclerosis risk: a total population-based case-control study. JAMA Neurol 72(1):40–48. https://doi.org/10.1001/jamaneurol.2014.3367

    Article  PubMed  Google Scholar 

  29. 29.

    Mariosa D, Hammar N, Malmstrom H, Ingre C, Jungner I, Ye W, Fang F, Walldius G (2017) Blood biomarkers of carbohydrate, lipid, and apolipoprotein metabolisms and risk of amyotrophic lateral sclerosis: a more than 20-year follow-up of the Swedish AMORIS cohort. Ann Neurol 81(5):718–728. https://doi.org/10.1002/ana.24936

    CAS  Article  PubMed  Google Scholar 

  30. 30.

    Taylan E, Tuncel EP (2016) Distribution of LDL subgroups in patients with hyperlipidemia. Turk J Med Sci 46(2):374–380. https://doi.org/10.3906/sag-1410-40

    CAS  Article  PubMed  Google Scholar 

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Acknowledgements

Dr. Charles Tzu-Chi Lee had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. This study was supported by grants from the Taiwan Motor Neuron Disease Association (TMND). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Author information

Author notes

  1. Dr. Ching-Piao Tsai and Dr. Johnny Kuang-Wu Lee contributed equally in this study.

Affiliations

  1. Department of Biotechnology, Asia University, Taichung, Taiwan

    Ching-Piao Tsai

  2. Beito Health Management Hospital, Taipei, Taiwan

    Ching-Piao Tsai

  3. General Education Center, University of Taipei, Taipei, Taiwan

    Johnny Kuang-Wu Lee

  4. Department of Health Promotion and Health Education, National Taiwan Normal University, 162, He-ping East Road, Section 1, Taipei, 106, Taiwan

    Charles Tzu-Chi Lee

Authors
  1. Ching-Piao Tsai
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  3. Charles Tzu-Chi Lee
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Contributions

CPT: developing the concept and design of the study; interpretation of data; and writing the first draft. JKWL: developing the concept and design of the study; interpretation of data; and writing the first draft. CTCL: acquisition of data; developing the concept and design of the study; analyzing of data; and writing the first draft.

Corresponding author

Correspondence to Charles Tzu-Chi Lee.

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Tsai, CP., Lee, J.KW. & Lee, C.TC. Type II diabetes mellitus and the incidence of amyotrophic lateral sclerosis. J Neurol 266, 2233–2243 (2019). https://doi.org/10.1007/s00415-019-09405-x

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Keywords

  • Amyotrophic lateral sclerosis
  • National Health Insurance Database
  • Serious Disabling Disease Database
  • Diabetes mellitus
  • Cohort study