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 initial TG (epsilon3/3, epsilon3/2 and epsilon2/2 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 = 0.801, 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.
Attia
N
N
Groupe Lipoproteines, Faculte de Medecine X., Paris, France.
Durlach
V
V
Roche
D
D
Paul
J L
JL
Soni
T
T
Zahouani
A
A
Landron
F
F
Labrousse
F
F
Leutenegger
M
M
Girard-Globa
A
A
D000368:Aged; D053305:Apolipoprotein C-III; D001056:Apolipoproteins C / Q000097:blood / Q000187:drug effects / Q000378:metabolism; D001629:Bezafibrate / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism; D002914:Chylomicrons / Q000097:blood / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D004041:Dietary Fats / Q000097:blood / Q000378:metabolism*; D004224:Diterpenes; D005230:Fatty Acids, Nonesterified / Q000097:blood; D006801:Humans; D008074:Lipoproteins / Q000097:blood / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period / Q000187:drug effects* / Q000502:physiology; D000084562:Retinyl Esters; D014280:Triglycerides / Q000097:blood / Q000378:metabolism*; D014801:Vitamin A / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism
D053305:Apolipoprotein C-III; D001056:Apolipoproteins C; D001786:Blood Glucose; D002914:Chylomicrons; D004041:Dietary Fats; D004224:Diterpenes; D005230:Fatty Acids, Nonesterified; D008074:Lipoproteins; D000084562:Retinyl Esters; D014280:Triglycerides; D014801:Vitamin A; C014794:retinol palmitate; D001629:Bezafibrate