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. Furthermore, the finding of two types of kinetic response to diabetic treatment suggests that underlying presumably familial abnormalities of lipoprotein transport are important in determining the effect of diabetes on VLDL-TG metabolism.
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism