[Lipid metabolism and insulin resistance--clinical aspects and pathobiochemistry]

About 3 decades ago insulin resistance has been described as the pathogenetic factor leading from abnormal fat metabolism to diabetes mellitus. Within the metabolic syndrome insulin resistance is related to the upper body (android) type of obesity, hypertriglyceridaemia, hypertension, and diabetes mellitus ("deadly quartet"). It precedes the development of arterial hypertension and the metabolic disorders. The pathomechanisms leading from obesity and hypertriglyceridaemia to insulin resistance may be described by the glucose fatty acid cycle of Randle et al. According to their metabolic scheme increased supply of fatty acids results in reduced glucose oxidation. Concomittantly hepatic glucose production is increased. On the other hand insulin resistance combined with hyperinsulinaemia may lead to an elevation of VLDL-triglycerides and to a decrease of HDL-cholesterol in blood, thus creating a vicious cycle, in which elevated VLDL-triglycerides reinforce insulin resistance via the glucose fatty acid cycle. Interventions to improve insulin sensitivity and thereby lower plasma insulin should reduce obesity and hypertriglyceridaemia by dietary treatment. They usually improve promptly diabetic metabolism. New developments in pharmacological inhibition of fatty acid oxidation are discussed.