Use of Dicarboxylic Acids in Type 2 Diabetes

Even number, medium chain dicarboxylic acids (DAs), naturally occurring in high plants, are a promising alternative energy substrate. Contrary to the homologous fatty acids, DAs are soluble in water as salts. They are β-oxidized providing Acetyl-CoAs and Succinyl-CoA, this latter an intermediate of the tricarboxylic acid cycle. Sebacic acid and dodecanedioic acid, DAs with 10 and 12 carbon atoms respectively, provide 6.6 kcal/g and 7.2 kcal/g each; therefore, their energy density is intermediate between glucose and fatty acids. DAs have been proved to be safe in both experimental animal and humans and their use has been recently proposed in diabetes. Studies in animals and humans with type 2 diabetes showed that oral administration of sebacic acid improved glycaemic control, probably by enhancing insulin sensitivity, and reduced hepatic gluconeogenesis and glucose output. Moreover, dodecanedioic acid intake reduced muscle fatigue during exercise in type-2 diabetes subjects, suggesting an improvement of energy utilization and "metabolic flexibility". In this article we will review the natural sources of DAs, their fate in animals and humans and their effect in improving glucose metabolism in type 2 diabetes. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.