Hypertriglyceridemia and carbohydrate intolerance: interrelations and therapeutic implications.

Atherosclerosis, the most frequent complication of diabetes, could be the result of hyperlipidemia, among other factors. Mounting evidence suggests that reducing the concentration of triglyceride-rich lipoprotein, which influences the production of the possibly atherogenic intermediate density lipoprotein (IDL), might diminish the circulating level of potentially atherogenic lipoproteins. Hypertriglyceridemia, even in the absence of obesity, is associated with insulin resistance. To compensate, pancreatic B cells respond to glucose challenge by producing hyperinsulinemia. If the B cells cannot respond adequately, carbohydrate intolerance ensues. Insulin-treated diabetics may also become hyperinsulinemic because routine insulin injection may not reflect physiologic need and because the insulin is administered peripherally rather than portally. Hyperinsulinemia increases the production of circulating triglyceride. It appears to do this in rats by causing the production of more triglyceride-rich lipoprotein particles rather than by increasing the triglyceride content of each particle. Further, at least in rats, the insulin-induced increase in triglyceride production requires the presence of supplementary dietary fructose. Hyperinsulinemia also increases the activity of adipose tissue lipoprotein lipase and the degradation of very low density lipoprotein (VLDL). The concentration of VLDL depends on balance of production and degradation. Accelerated VLDL degradation leads to an increase in IDL production. Because there is mounting evidence that IDL may be atherogenic, this cycle could accelerate atherogenesis. As such, it is reasonable to postulate that reducing the concentration of triglyceride-rich lipoproteins would break this cycle and would diminish the circulating level of potentially atherogenic lipoproteins.