The
glycogen storage disorders (GSD)-I, -III, -VI and -VIII are associated with hypertriglyceridaemia or mixed hyperlipidaemia which poses the question whether these patients have an increased risk for
atherosclerosis. The atherogenicity of
triglycerides has remained controversial, while increased plasma
cholesterol levels are generally accepted as a significant risk factor for
coronary heart disease. However, clinical data show that one has to differentiate between metabolic conditions where
triglycerides are atherogenic and those which are not significantly related to early onset of
atherosclerosis but may cause other disorders such as
pancreatitis. Among the disorders of carbohydrate metabolism patients with
diabetes mellitus frequently have enhanced plasma
triglycerides associated with a higher risk for
coronary heart disease, while patients with certain types of
glycogen storage disease have high
triglyceride levels but do not seem to have an enhanced risk for
atherosclerosis. Here we have compared the biochemical abnormalities and the atherogenic risk of three different disorders of
glucose metabolism including GSD-I (glucose-6-phosphatase deficiency),
favism (glucose-6-phosphate dehydrogenase deficiency), and
diabetes mellitus which are related to either hyper- or hypolipidaemia. The available data indicate that
glucose-6-phosphate (Glc-6-P) is a central molecule in cellular
glucose metabolism which critically influences
pentose phosphate cycle activity and, via NADPH2-generation, regulates
glutathione peroxidase activity for radical detoxification and also
cholesterol and
triglyceride synthesis. Radical detoxification is a major protective factor for cell membrane integrity and together with an appropriate renewal of
membrane lipids may protect against the development of
atherosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)