Evidence for multiple causality in the development of diabetic hypertriglyceridaemia.

The relationship between varying degrees of insulin deficiency and hypertriglyceridaemia in rats have been examined. Rats were studied 7--10 days after injection with streptozotocin, and plasma glucose concentrations used to classify rats as having either moderate (200--350 mg/dl) or severe diabetes (< 350 mg/dl). A 2- to 3-fold rise in plasma triglyceride (TG) concentration developed in six week old insulin deficient rats associated with elevated plasma non esterified fatty acid (NEFA) concentrations and decreased very low density lipoprotein secretion. Perfused liver from six week old rats with either moderate or severe diabetes were incapable of increasing hepatic TG secretion when perfusate NEFA concentrations were raised from 0.4 to 1.8 mmol/l. In one year old, spontaneously obese rats, an equivalent degree of hypertriglyceridaemia could be produced with a lesser degree of insulin deficiency, and in this instance very low density lipoprotein secretion was increased over control values. Hepatic TG secretion by perfused livers from these rats with moderate diabetes approximately doubled when perfusate NEFA condentration was raised from 0.40 to 0.85 mmol/l. These results emphasize the complex causality of diabetic hypertriglyeridaemia in situations characterised by comparable degrees of fasting hyperglycaemia.