stigmastanol and Diabetes-Mellitus--Type-2

The basis for treatment of lipid disorders in patients with non-insulin-dependent diabetes mellitus is weight reduction by diet and exercise, and additional control of glycaemic condition with oral antidiabetics, alone or in combination with insulin. Hypercholesterolaemic, mildly hypertriglyceridaemic non-insulin-dependent diabetes mellitus patients respond to cholesterol malabsorption caused by dietary sitostanol ester margarine, while long-term statin treatment of respective coronary patients significantly lowers the recurrence of coronary events, in addition to improving the lipid disorder. However, no information is available concerning the preventive effect of long-term improvement of lipid disorders in non-insulin-dependent diabetes mellitus patients without coronary heart disease, or in patients with the 'classical' type of diabetic lipid disorder, that is, hypertriglyceridaemia with low HDL and normal-low LDL-cholesterol levels. In this group of patients, beneficial lipid effects can be obtained (although perhaps not normalization) with fibrates alone or, especially, in combination with current statins.

Topics: Anticholesteremic Agents; Diabetes Mellitus, Type 2; Diet; Exercise; Humans; Hyperlipidemias; Hypoglycemic Agents; Hypolipidemic Agents; Sitosterols

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.

Topics: Absorption; Anticholesteremic Agents; Blood Specimen Collection; Cholesterol; Diabetes Mellitus, Type 2; Double-Blind Method; Humans; Hypercholesterolemia; Lipoproteins; Male; Middle Aged; Patient Selection; Pravastatin; Sitosterols; Triglycerides

Cholesterol absorption and metabolism and LDL and HDL kinetics were investigated in 11 hypercholesterolaemic non-insulin-dependent diabetic men off and on a hypolipidaemic treatment with sitostanol ester, (3 g sitostanol daily) dissolved in rapeseed oil margarine, by a double-blind crossover study design. Serum total, VLDL and LDL cholesterol and apoprotein B fell significantly by 6 +/- 2, 12 +/- 6, 9 +/- 3 and 6 +/- 2%, mean +/- SEM, and HDL cholesterol was increased by 11 +/- 4% (p < 0.05) by sitostanol ester. LDL cholesterol and apoprotein B were significantly decreased in the dense (1.037-1.055 g/ml), but not light, LDL subfraction due to a significantly diminished transport rate for LDL apoprotein B, while the fractional catabolic rate was unchanged. HDL kinetics, measured with autologous apoprotein A I, was unaffected by sitostanol ester. Cholesterol absorption efficiency was markedly reduced from 25 +/- 2 to 9 +/- 2% (p < 0.001) during sitostanol ester followed by proportionately decreased serum plant sterol proportions. Cholesterol precursor sterol proportions in serum, fecal neutral sterol excretion, and cholesterol synthesis, cholesterol transport, and biliary secretion were all significantly increased by sitostanol ester. We conclude that the sitostanol ester-induced decrease in cholesterol absorption compensatorily stimulated cholesterol synthesis, had no effect on fractional catabolic rate, but decreased transport rate for LDL apoprotein B so that serum total, VLDL and LDL cholesterol levels were decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Apolipoproteins A; Blood Glucose; Body Mass Index; Brassica; Cholesterol; Cholesterol, Dietary; Cholesterol, HDL; Cholesterol, LDL; Cross-Over Studies; Diabetes Mellitus, Type 2; Double-Blind Method; Energy Intake; Fatty Acids, Monounsaturated; Glycated Hemoglobin; Humans; Hypercholesterolemia; Lipoproteins; Male; Margarine; Middle Aged; Phospholipids; Plant Oils; Rapeseed Oil; Sialic Acids; Sitosterols; Triglycerides; Vitamin E