Effects of inhibiting cholesterol absorption and synthesis on cholesterol and lipoprotein metabolism in hypercholesterolemic non-insulin-dependent diabetic men.
Effectiveness of a simultaneous inhibition of cholesterol absorption and synthesis, caused by sitostanol ester margarine and pravastatin, was studied to control mild hypercholesterolemia in men with non-insulin-dependent diabetes mellitus (NIDDM) (n = 8). Margarine, 24 g daily, was a basal dietary treatment. Four 7-week intervention periods included margarine, sitostanol (3 g/day) ester margarine, pravastatin (40 mg/day), and sitostanol ester margarine plus pravastatin in a random order. Pravastatin lowered serum total (-32%) and LDL cholesterol (-38%) and apolipoprotein B (-39%) because of enhanced removal (+20%) and decreased production (-26%) of LDL apolipoprotein B, and reduced synthesis (-9%) and turnover (-8%) of cholesterol, which resulted in reduced biliary cholesterol seretion (-18%). Even though serum triglycerides were lowered by 28%, VLDL, IDL, and light and dense LDL became triglyceride-enriched. Despite increasing cholesterol synthesis, sitostanol lowered LDL cholesterol (-14%) by inhibiting cholesterol absorption (-68%) and LDL apolipoprotein B production rate (-20%). Combination of pravastatin and sitostanol ester lowered serum total, VLDL, IDL, and LDL cholesterol and LDL apolipoprotein B by the highest rate, 35%, 50%, 35%, 44%, and 45% from the control margarine period, respectively, because of reduced apolipoprotein B transport rate (but unchanged removal), in both the total and dense LDL subfractions. HDL cholesterol and apolipoprotein A-I kinetics were unchanged. In spite of decreased absorption, cholesterol synthesis was not compensatorily increased. In conclusion, simultaneous inhibition of cholesterol absorption and synthesis lowers LDL cholesterol and apolipoprotein B by 44-45% solely through inhibition of LDL apolipoprotein B production rate in hypercholesterolemic NIDDM patients. A combination of statin to sitostanol ester margarine-resistant patients offers a safe and effective measure to normalize abnormally high cholesterol values, probably with a lowered statin dose.
Gylling
H
H
Department of Medicine, University of Helsinki, Finland.
Miettinen
T A
TA
D000042:Absorption; D000924:Anticholesteremic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001800:Blood Specimen Collection; D002784:Cholesterol / Q000097:blood* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000188:drug therapy; D004311:Double-Blind Method; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy / Q000503:physiopathology*; D008074:Lipoproteins / Q000097:blood* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D017035:Pravastatin / Q000494:pharmacology / Q000627:therapeutic use; D012855:Sitosterols / Q000494:pharmacology / Q000627:therapeutic use; D014280:Triglycerides / Q000097:blood / Q000378:metabolism
D000924:Anticholesteremic Agents; D008074:Lipoproteins; D012855:Sitosterols; D014280:Triglycerides; D002784:Cholesterol; C021255:stigmastanol; D017035:Pravastatin