The links between diabetes mellitus and amyotrophic lateral sclerosis.

ALS etiology and prognostic factors are mostly unknown. Metabolic diseases and especially diabetes mellitus (DM) have been variously related to ALS. However, pieces of evidence have been variegated and often conflicting so far. This review aims to give an overview of recent contributions focusing on the relationship between DM and ALS. DM seems to reduce the risk of developing ALS if diagnosed at a younger age; conversely, when diagnosed at an older age, DM seems protective against ALS. Such a relationship was not confirmed in Asian countries where DM increases the risk of ALS independently of the age of onset. Interestingly, DM does not affect ALS prognosis, possibly weakening the potential causal relationship between the two diseases. However, since most studies are observational, it is difficult to state the exact nature of such a relationship and several hypotheses have been made. A recent study using Mendelian randomization suggested that DM is indeed protective against ALS in the European population. However, these analyses are not without limits and further evidence is needed. DM is usually the core of a larger metabolic syndrome. Thus, other metabolic changes such as dyslipidemia, body mass index, and cardiovascular diseases should be collectively considered. Finally, hypermetabolism usually found in ALS patients should be considered too since all these metabolic changes could be compensation (or the cause) of the higher energy expenditure.