Abnormal regulation of carbohydrate metabolism in motor neurone disease.

In this study, circulating concentrations of intermediary metabolites were measured in eight non-obese subjects with motor neurone disease in the basal (postabsorptive) state, and after a 75 g oral glucose challenge. Eight healthy subjects of similar age and body mass index served as controls. Basal pyruvate concentration was significantly elevated in the subjects with motor neurone disease (p less than 0.02). After oral glucose ingestion, overall levels of pyruvate (p less than 0.01) and lactate (p less than 0.05) were significantly higher in these subjects. Blood glucose concentrations fulfilled the criteria diagnostic of impaired glucose tolerance in six of the eight subjects with motor neurone disease (WHO, 1985). Cumulative insulin levels were slightly higher in these subjects and peak insulin response was delayed (120 min vs. 60 min) relative to the healthy controls. Circulating concentrations of alanine, glycerol, non-esterified fatty acids and total ketone bodies were similar between groups. These results confirm that impaired glucose tolerance is a common feature of motor neurone disease. Furthermore, our data indicate disordered regulation of both pyruvate and lactate metabolism, consistent with reports of defective skeletal muscle pyruvate oxidation in individuals with this disorder. In contrast, our results indicate that the regulation of lipolysis and ketone body metabolism is unimpaired in motor neurone disease.