THE EFFECT OF AN ANTILIPOLYTIC AGENT (ACIPIMOX) ON THE INSULIN-RESISTANCE OF LIPID AND GLUCOSE-METABOLISM IN HYPERTRIGLYCERIDEMIC PATIENTS

Hypertriglyceridaemia is associated with insulin resistance of both li pid and glucose metabolism. It is not known whether the insulin resist ance affects both glucose oxidation and glycogen formation. To study t he oxidative and non-oxidative pathways of non-esterified fatty acids (NEFA) and glucose metabolism, eight male hypertriglyceridaemic subjec ts were studied during insulin infusion (75 and 340 pmol/m(2).min) in combination with indirect calorimetry and infusions of [3-H-3]glucose and [1-C-14]palmitate before and after 4 weeks of treatment with the a ntilipolytic agent acipimox (250 mg three times daily). Compared with eight healthy subjects the hypertriglyceridaemic subjects were resista nt to the antilipolytic effect of insulin, both in the basal state (P < 0.05) and during insulin infusion (P < 0.05). This was associated wi th impaired insulin-stimulated glucose uptake (P < 0.05), predominantl y in the non-oxidative pathway (P < 0.05). Acipimox decreased basal NE FA concentrations (P < 0.01) and reduced lipid oxidation during low-do se insulin infusion (P < 0.05). Glucose uptake, predominantly glycogen formation, was stimulated by acipimox (P < 0.05). In conclusion, the insulin resistance of glucose metabolism associated with hypertriglyce ridaemia is largely due to a defect in non-oxidative glucose metabolis m. Acipimox improves glucose metabolism both by affecting glucose oxid ation (low-dose insulin) and non-oxidative glucose metabolism (high-do se insulin).