The effect of diabetic control on very low-density lipoprotein--triglyceride metabolism in patients with type II diabetes mellitus and marked hypertriglyceridemia

We examined the effect of diabetic control on very low-density lipoprotein-triglyceride (VLDL-TG) metabolism in six patients with type II (noninsulin-dependent) diabetes mellitus and marked hypertriglyceridemia. VLDL-TG transport was determined using 3H-glycerol as an endogenous precursor of VLDL-TG, and the resultant kinetic data were evaluated by multicompartmental analysis. Studies were performed in the hypertriglyceridemic diabetic subjects during poor diabetic control and again after 3 months of diabetic treatment, and the results were compared to studies in nondiabetic normolipidemic subjects and nondiabetic subjects with familial forms of hypertriglyceridemia. In the poorly controlled diabetics, mean VLDL-TG synthesis was threefold higher than in the normolipidemic subjects, and the mean fractional catabolic rate (FCR) of VLDL-TG was only one-third of the normals. With diabetic treatment, plasma triglyceride levels fell by more than 50%, but remained fourfold higher than the normals. This was associated with a decrease in mean VLDL-TG synthesis to a level similar to that observed in the genetic hyperlipidemic subjects, but still 2.6-fold higher than the normals. In addition, the mean FCR rose after diabetic control to a level slightly above that of the genetic hyperlipidemic subjects, but remained less than one-half of the normal value. However, the response of VLDL-TG kinetics to diabetic treatment was not uniform. In four subjects, control of hyperglycemia ameliorated the hypertriglyceridemia primarily by decreasing VLDL-TG overproduction. In the other two subjects, diabetic treatment had a greater effect on the FCR than an overproduction of VLDL-TG. Thus, in this select group of diabetic, hypertriglyceridemic subjects, poor diabetic control contributed to both VLDL-TG overproduction and low FCRs. Failure of diabetic treatment to restore VLDL-TG kinetic parameters to normal suggests that the hypertriglyceridemia was due not only to diabetes mellitus but also to an additional abnormality affecting lipoprotein metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)