LIPID-METABOLISM AND INSULIN-RESISTANCE - CLINICAL OBSERVATIONS AND PATHOBIOCHEMISTRY

About 3 decades ago insulin resistance has been described as the patho genetic factor leading from abnormal fat metabolism to diabetes mellit us. Within the metabolic syndrome insulin resistance is related to the upper body (android) type of obesity, hypertriglyceridaemia, hyperten sion, and diabetes mellitus (''deadly quartet''). It preceds the devel opment of arterial hypertension and the metabolic disorders. The patho mechanisms leading from obesity and hypertriglyceridaemia to insulin r esistance may be described by the glucose fatty acid cycle of Randle e t al. According to their metabolic scheme increased supply of fatty ac ids results in reduced glucose oxidation. Concomittantly hepatic gluco se production is increased. On the other hand insulin resistance combi ned with hyperinsulinaemia may lead to an elevation of VLDL-triglyceri des and to a decrease of HDL-cholesterol in blood, thus creating a vic ious cycle, in which elevated VLDL-triglycerides reinforce insulin res istance via the glucose fatty acid cycle. Interventions to improve ins ulin sensitivity and thereby lower plasma insulin should reduce obesit y and hypertriglyceridaemia by dietary treatment. They usually improve promptly diabetic metabolism. New developments in pharmacological inh ibition of fatty acid oxidation are discussed.