Diabetes Mellitus and Amyotrophic Lateral Sclerosis: A Systematic Review.

Laura Ferri,Margherita Capasso,Marco Onofrj,Filomena Barbone,Laura Bonanni,Damiano D’Ardes,Francesco Cipollone,Claudia Carrarini,Marianna Gabriella Rispoli,Antonio Di Muzio,Paola Ajdinaj

doi:10.3390/biom11060867

Laura Ferri, Margherita Capasso + Show 9 more

Open Access

https://doi.org/10.3390/biom11060867

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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.

Highlights

IntroductionAmyotrophic Lateral Sclerosis (ALS) is a degenerative disorder of unknown cause which affects the motor neurons of the cerebral cortex, brainstem, and spinal cord [1,2,3,4]
To elucidate the molecular mechanisms underlying the extra-neural pathology of Amyotrophic Lateral Sclerosis (ALS), some authors focus on TAR DNA-binding protein 43 kDa (TDP-43) which is found in 90–95%
We describe how the multiple attempts to shed light on the relationship between Diabetes Mellitus (DM) and ALS may be hindered by several shortcomings

Summary

Introduction

Amyotrophic Lateral Sclerosis (ALS) is a degenerative disorder of unknown cause which affects the motor neurons of the cerebral cortex, brainstem, and spinal cord [1,2,3,4]. The primary triggers for motor neuron degeneration in ALS remain elusive, research in patients and in SOD1 mutant mice models has revealed several processes that are likely to contribute to the pathology, including inflammation and toxic glial activation [5,6], mitochondrial dysfunction [7,8], and oxidative stress [9,10]. Several studies demonstrated that two-thirds of ALS patients develop a stable hypermetabolism during the course of the disease [11,14,15,16] which has been linked to a worse. There is no consensus in literature and, several hypothesis were examined, the mechanisms underlying hypermetabolism are still unclear [11,14,18,19,20]

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