Diabetes Mellitus and Amyotrophic Lateral Sclerosis: A Systematic Review

Overview

Journal Biomolecules

Publisher MDPI

Specialties Biochemistry
Molecular Biology

Date 2021 Jul 2

PMID 34200812

Citations 5

Authors

Laura Ferri

Paola Ajdinaj

Marianna Gabriella Rispoli

Claudia Carrarini

Filomena Barbone

Damiano DArdes

Margherita Capasso

Antonio Di Muzio

Francesco Cipollone

Marco Onofrj

Laura Bonanni

Affiliations

Soon will be listed here.

Abstract

Background: Amyotrophic Lateral Sclerosis (ALS) is a degenerative disorder which affects the motor neurons. Growing evidence suggests that ALS may impact the metabolic system, including the glucose metabolism. Several studies investigated the role of Diabetes Mellitus (DM) as risk and/or prognostic factor. However, a clear correlation between DM and ALS has not been defined. In this review, we focus on the role of DM in ALS, examining the different hypotheses on how perturbations of glucose metabolism may interact with the pathophysiology and the course of ALS.

Methods: We undertook an independent PubMed literature search, using the following search terms: ((ALS) OR (Amyotrophic Lateral Sclerosis) OR (Motor Neuron Disease)) AND ((Diabetes) OR (Glucose Intolerance) OR (Hyperglycemia)). Review and original articles were considered.

Results: DM appears not to affect ALS severity, progression, and survival. Contrasting data suggested a protective role of DM on the occurrence of ALS in elderly and an opposite effect in younger subjects.

Conclusions: The actual clinical and pathophysiological correlation between DM and ALS is unclear. Large longitudinal prospective studies are needed. Achieving large sample sizes comparable to those of common complex diseases like DM is a challenge for a rare disease like ALS. Collaborative efforts could overcome this specific issue.

Citing Articles

Clinical and Sociodemographic Factors Related to Amyotrophic Lateral Sclerosis in Spain: A Pilot Study.

Proano B, Cuerda-Ballester M, Daroqui-Pajares N, Del Moral-Lopez N, Segui-Sala F, Marti-Serer L J Clin Med. 2024; 13(19).

PMID: 39407861 PMC: 11476538. DOI: 10.3390/jcm13195800.

Impact of diabetes mellitus on the respiratory function of amyotrophic lateral sclerosis patients.

Pinto S, Oliveira Santos M, Gromicho M, Swash M, de Carvalho M Eur J Neurol. 2023; 31(2):e16129.

PMID: 37955564 PMC: 11235781. DOI: 10.1111/ene.16129.

Risk factors of amyotrophic lateral sclerosis: a global meta-summary.

Duan Q, Jiang Z, Su W, Gu X, Wang H, Cheng Y Front Neurosci. 2023; 17:1177431.

PMID: 37168926 PMC: 10165003. DOI: 10.3389/fnins.2023.1177431.

Key Disease Mechanisms Linked to Amyotrophic Lateral Sclerosis in Spinal Cord Motor Neurons.

Bottero V, Santiago J, Quinn J, Potashkin J Front Mol Neurosci. 2022; 15:825031.

PMID: 35370543 PMC: 8965442. DOI: 10.3389/fnmol.2022.825031.

Amyotrophic Lateral Sclerosis: A Diet Review.

DAntona S, Caramenti M, Porro D, Castiglioni I, Cava C Foods. 2021; 10(12).

PMID: 34945679 PMC: 8702143. DOI: 10.3390/foods10123128.

References

Dandona P, Aljada A, Ghanim H, Mohanty P, Tripathy C, Hofmeyer D . Increased plasma concentration of macrophage migration inhibitory factor (MIF) and MIF mRNA in mononuclear cells in the obese and the suppressive action of metformin. J Clin Endocrinol Metab. 2004; 89(10):5043-7. DOI: 10.1210/jc.2004-0436. View

Desport J, Preux P, Magy L, Boirie Y, Vallat J, Beaufrere B . Factors correlated with hypermetabolism in patients with amyotrophic lateral sclerosis. Am J Clin Nutr. 2001; 74(3):328-34. DOI: 10.1093/ajcn/74.3.328. View

Barber S, Mead R, Shaw P . Oxidative stress in ALS: a mechanism of neurodegeneration and a therapeutic target. Biochim Biophys Acta. 2006; 1762(11-12):1051-67. DOI: 10.1016/j.bbadis.2006.03.008. View

Cassina P, Cassina A, Pehar M, Castellanos R, Gandelman M, de Leon A . Mitochondrial dysfunction in SOD1G93A-bearing astrocytes promotes motor neuron degeneration: prevention by mitochondrial-targeted antioxidants. J Neurosci. 2008; 28(16):4115-22. PMC: 3844766. DOI: 10.1523/JNEUROSCI.5308-07.2008. View

Chelstowska B, Kuzma-Kozakiewicz M . Biochemical parameters in determination of nutritional status in amyotrophic lateral sclerosis. Neurol Sci. 2020; 41(5):1115-1124. DOI: 10.1007/s10072-019-04201-x. View

Mandrioli J, Malerba S, Beghi E, Fini N, Fasano A, Zucchi E . Riluzole and other prognostic factors in ALS: a population-based registry study in Italy. J Neurol. 2018; 265(4):817-827. DOI: 10.1007/s00415-018-8778-y. View

Li Y, Pericak-Vance M, Haines J, Siddique N, McKenna-Yasek D, Hung W . Apolipoprotein E is associated with age at onset of amyotrophic lateral sclerosis. Neurogenetics. 2005; 5(4):209-13. DOI: 10.1007/s10048-004-0193-0. View

Nutini M, Frazzini V, Marini C, Spalloni A, Sensi S, Longone P . Zinc pre-treatment enhances NMDAR-mediated excitotoxicity in cultured cortical neurons from SOD1(G93A) mouse, a model of amyotrophic lateral sclerosis. Neuropharmacology. 2010; 60(7-8):1200-8. DOI: 10.1016/j.neuropharm.2010.11.001. View

Stallings N, Puttaparthi K, Luther C, Burns D, Elliott J . Progressive motor weakness in transgenic mice expressing human TDP-43. Neurobiol Dis. 2010; 40(2):404-14. DOI: 10.1016/j.nbd.2010.06.017. View

10.

Goodall E, Morrison K . Amyotrophic lateral sclerosis (motor neuron disease): proposed mechanisms and pathways to treatment. Expert Rev Mol Med. 2006; 8(11):1-22. DOI: 10.1017/S1462399406010854. View

11.

Kioumourtzoglou M, Rotem R, Seals R, Gredal O, Hansen J, Weisskopf M . Diabetes Mellitus, Obesity, and Diagnosis of Amyotrophic Lateral Sclerosis: A Population-Based Study. JAMA Neurol. 2015; 72(8):905-11. PMC: 4975611. DOI: 10.1001/jamaneurol.2015.0910. View

12.

Mariosa D, Kamel F, Bellocco R, Ronnevi L, Almqvist C, Larsson H . Antidiabetics, statins and the risk of amyotrophic lateral sclerosis. Eur J Neurol. 2020; 27(6):1010-1016. PMC: 10957794. DOI: 10.1111/ene.14190. View

13.

Ferri A, Coccurello R . What is "Hyper" in the ALS Hypermetabolism?. Mediators Inflamm. 2017; 2017:7821672. PMC: 5610793. DOI: 10.1155/2017/7821672. View

14.

Al-Chalabi A, Hardiman O . The epidemiology of ALS: a conspiracy of genes, environment and time. Nat Rev Neurol. 2013; 9(11):617-28. DOI: 10.1038/nrneurol.2013.203. View

15.

Stallings N, Puttaparthi K, Dowling K, Luther C, Burns D, Davis K . TDP-43, an ALS linked protein, regulates fat deposition and glucose homeostasis. PLoS One. 2013; 8(8):e71793. PMC: 3742534. DOI: 10.1371/journal.pone.0071793. View

16.

Smith E, Shaw P, De Vos K . The role of mitochondria in amyotrophic lateral sclerosis. Neurosci Lett. 2017; 710:132933. DOI: 10.1016/j.neulet.2017.06.052. View

17.

Van Everbroeck B, Croes E, Pals P, Dermaut B, Jansen G, van Duijn C . Influence of the prion protein and the apolipoprotein E genotype on the Creutzfeldt-Jakob Disease phenotype. Neurosci Lett. 2001; 313(1-2):69-72. DOI: 10.1016/s0304-3940(01)02264-9. View

18.

Fergani A, Oudart H, Gonzalez De Aguilar J, Fricker B, Rene F, Hocquette J . Increased peripheral lipid clearance in an animal model of amyotrophic lateral sclerosis. J Lipid Res. 2007; 48(7):1571-80. PMC: 1974855. DOI: 10.1194/jlr.M700017-JLR200. View

19.

Logroscino G . Motor neuron disease: Are diabetes and amyotrophic lateral sclerosis related?. Nat Rev Neurol. 2015; 11(9):488-90. DOI: 10.1038/nrneurol.2015.145. View

20.

Li Y, Hauser M, Scott W, Martin E, Booze M, Qin X . Apolipoprotein E controls the risk and age at onset of Parkinson disease. Neurology. 2004; 62(11):2005-9. DOI: 10.1212/01.wnl.0000128089.53030.ac. View