Post-prandial metabolism of triglyceride-rich lipoproteins in non-insulin-dependent diabetic patients before and after bezafibrate treatment

Retarded post-prandial (pp) lipid clearance is potentially a major component of the increased cardiovascular risk incurred by hypertriglyceridaemic non-insulin-dependent diabetic mellitus (NIDDM) patients. The effect of bezafibrate (Bz, 400 mg per day for 5 weeks on chylomicron (CM) and remnant clearance after loads of 100 g of fat and vitamin A was therefore explored in 10 male patients (glycaemia 11.9 ±3.3 TG 4.5 ±2.4 mmol L^–1). In all subjects CM-TG and retinyl palmitate (RP) were reduced by 50%, but 8-h non-CM (remnant) RP decreased only in initially mildly hypertriglyceridaemic subjects (−35%, P  <0.05), while in three patients with very elevated initialTG (ε3/3, ε_3/2 and ε_2/2 genotypes) 8-h remnant RP increased by 100%. The decrease in pp CM-TG correlated with that of fasting Sf 20–400 ( r  = 0.686, P  = 0.026), suggesting that improved lipolysis was a major determinant of hypolipidaemic effect. Apo CIII synthesis is known to be depressed by Bz: concentrations were lower under Bz ( P  <0.05). A positive correlation ( r  =0.880, P  <0.001) with fasting TG before treatment and its disappearance after treatment suggested an involvement of high concentrations with hypertriglyceridaemia. Post-prandial non-esterified fatty acids were decreased by 35 in correlation with a significant (−19%, P  <0.05) improvement in fasting glycaemia ( r  =-.801, P  <0.005). These results suggest that Bz acts both on lipolysis and on removal of CM remnants, but that removal can become saturated when lipolysis is massively improved.