Impaired glucose tolerance in patients with amyotrophic lateral sclerosis

Abstract

Our objectives were to analyse carbohydrate metabolism in a series of ALS patients and to examine potential association with parameters of lipid metabolism and clinical features. Glucose tolerance was assessed by the oral glucose tolerance test in 21 non-diabetic ALS patients and compared with 21 age- and sex-matched normal subjects. Lipids and lactate/pyruvate ratio, levels of pro-inflammatory cytokines (tumour necrosis factor-alpha and interleukin-6) and adipocytokines (leptin and adiponectin) were also measured in ALS patients. Mann-Whitney U-tests analysed continuous data and Fisher's exact tests assessed categorical data. Blood glucose determined 120 min after the glucose bolus was significantly higher in patients with ALS (7.41 mmol/l+/-1.68) compared to controls (6.05+/-1.44, p=0.006). ALS patients with impaired glucose tolerance (IGT) according to WHO criteria (n=7, 33%) were more likely to have elevated free fatty acids (FFA) levels compared to patients with normal glucose tolerance (0.77 nmol/l+/-0.30 vs. 0.57+/-0.19, p=0.04). IGT was not associated with disease duration or severity. In conclusion, patients with ALS show abnormal glucose tolerance that could be associated with increased FFA levels, a key determinant of insulin resistance. The origin of glucose homeostasis abnormalities in ALS may be multifactorial and deserves further investigation.

Patients with elevated triglyceride and cholesterol serum levels have a prolonged survival in amyotrophic lateral sclerosis

“…The results also seem to confirm early reports of abnormalities of lipid and carbohydrate metabolism in ALS patients [11][12][13]. Pradat et al [14] also recently observed an impaired glucose tolerance of ALS patients compared to controls. Jawaid et al [15] reported that diabetes mellitus was associated with a 4-year later onset of ALS.…”

Altered Metabolic Homeostasis in Amyotrophic Lateral Sclerosis: Mechanisms of Energy Imbalance and Contribution to Disease Progression

“…The findings of reduced body fat mass (FM) in ALS patients [128] and reduced adipose tissue accumulation in animal models of ALS [17] have sparked the hypothesis that there is altered lipolysis in ALS. This is supported by the finding of elevated plasma FFA in patients with ALS [113,115] as well as an increased rate of lipolysis [129] and reduced FFA uptake and storage [17] in animal models. In addition to accelerated lipolysis, there is evidence to suggest that the use of glycogen (an important alternative fuel reserve stored in liver and skeletal muscle which yields glucose molecules) is decreased in ALS.…”

“…Since the 1960s, there have been reports of impaired glucose tolerance and insulin resistance in ALS [9,11,109,110,111,112,113]. The possibility of impaired function of insulin is of particular interest in ALS because reduced glucose availability could exacerbate neuronal dysfunction, particularly in the CNS, which relies predominantly on glucose as fuel.…”

“…However, the incidence of abnormal glucose tolerance tests in ALS patients ranges from 19-72% [9,113,115,116,117,118], and therefore subtle alterations in glucose handling could occur in ALS. Abnormal glucose metabolism does not appear to affect survival or disease severity [114,119]; however, one Taiwanese study reported an increased risk of ALS in those with DM [120].…”

MicroRNA regulators of cholinergic signaling link neuromuscular, cardiac and metabolic systems

“…Alongside other metabolic features, augmenting glucose intolerance is considered a sign of deteriorating and dysregulated metabolic homeostasis progressing along with the disease (66,72). Interestingly, recent research has identified miR-206's involvement in the downregulation of enzymes involved in metabolism.…”