Plasma triglyceride transport kinetics in diabetes mellitus

Abstract

Plasma endogenous triglyceride transport has been measured in 74 adult patients with different types of diabetes and compared to similar data obtained in 35 healthy normoglyceridemic control subjects. The diabetic material was divided into subgroups by a number of criteria including ketoacidosis, insulin-dependence, relative body weight, control of blood glucose, and severity of hypertriglyceridemia. In ketoacidosis, a marked elevation of plasma triglyceride production rate was the rule, and this probably accounted for the moderate hypertriglyceridemia even though the fractional transport was simultaneously lowered. In uncontrolled but nonketotic juvenile-type diabetes the mean plasma triglyceride turnover rate and concentration were both significantly increased while the fractional turnover was in most cases within normal range. When the disease was brought into good control by insulin the production rate decreased but not completely in line with blood glucose. Patients with adult-onset-type diabetes showed also an increase of triglyceride turnover rate, and the magnitude of hypertriglyceridemia was consistent with this increment so that most patients were “on line” of the enzyme kinetic Michaelis curves extrapolated from the normal material. On the other hand, of nonketotic diabetics with severe hyperglyceridemia (more than 4.0 m M) some had an increased turnover rate, while others were characterized by a normal production rate. Therefore, it is probable that one minor group of diabetics has a true removal defect, while in other forms of diabetes, the hypertriglyceridemia, if present, is primarily due to enhanced hepatic secretion of triglycerides into plasma. The exogenous fat tolerance was tested in 15 uncontrolled diabetics and 10 control subjects with intravenous intralipid emulsion. The fractional disappearance rate was either normal or decreased in diabetes but, when compared at similar basal plasma triglyceride concentration, there was no difference in the elimination of exogenous particulate fat between diabetics and nondiabetics. The different mechanisms of hypertriglyceridemia associated with diabetes are discussed on the basis of the results obtained in this study. In this connection a new concept on the regulation of removal kinetics by plasma triglyceride production rate is suggested.