Postprandial concentrations and distribution of apo C-III in type 2 diabetic patients. Effect of bezafibrate treatment

Apo C-III plays a key role in the metabolism of triglyceride-rich lipoproteins. It has recently been implicated as a potential determinant of the triglyceride (TG) lowering effect of fibrates, which down-regulate its expression. This hypothesis has been explored in ten moderately hypertriglyceridemic (TG 4.50±2.40 mmol/l) male type 2 diabetic patients tested with a lipid load before and after 4 weeks of treatment with 400 mg bezafibrate daily. Treatment lowered apo C-III concentrations by 20%, mainly in VLDL. Postprandially, apo C-III was transferred to chylomicrons in proportion to their TG content exclusively from HDL. VLDL retained their apo C-III and the apo C-III:TG ratio decreased as TG contents increased. At the end of the absorptive period (8 h) HDL did not recover the totality of their apo C-III (net loss 19 and 28% respectively before and after treatment, P<0.0001 for time effect). Bezafibrate lowered apo E by 33% (P<0.03). The apo C-III:apo E ratio did not vary significantly under treatment but underwent a postprandial decrease: 13% before and 18% (P=0.01) after treatment. These results indicate that repression of apo C-III expression and lowering of the apo C-III:E ratio are not likely mechanisms for the lipid-lowering effects of fibrates in type 2 diabetic patients. The potent effects on postprandial lipemia are suggestive of an apo C-III-independent stimulation of lipolysis.