Effects of acarbose on serum lipoproteins in healthy individuals during prolonged administration of a fiber-free formula diet

The effects of the disaccharidase inhibitor acarbose on serum lipoprotein lipid concentrations were investigated in healthy subjects during prolonged feeding of a fiber-free formula diet. Acarbose was shown to decrease cholesterol and fasting triglyceride concentrations, whereas the postprandial increment of triglycerides was not diminished. The response of fasting triglycerides to acarbose treatment appeared to be related to dietary fat intake, but not to the drug-induced reduction of postprandial glucose and insulin concentrations. Both the triglyceride and the cholesterol lowering efficacy were less pronounced with a higher amount of saturated fat than with a lower intake of fat mainly composed of polyunsaturated fatty acids. The decrease in total cholesterol was shown to be a consequence of a significant reduction in low density lipoprotein (LDL) cholesterol. Since high density lipoprotein (HDL) cholesterol concentrations remained unaltered, the ratio of HDL/LDL cholesterol changed in a beneficial way.     

Effect of exercise training and diet modification on serum lipids and lipoproteins in coronary artery disease patients treated with thiazides

The effects of chronic exercise training and diet modification on serum lipids and lipoproteins were measured in 17 hypertensive males and 41 normotensive males with documented coronary artery disease (CAD). Exercise consisted of aerobic activities which were performed at approximately 75-85% of the symptom-limited maximum heart rate for 30-40 minutes, three times weekly for 3 months. Each participant's diet was also controlled, the recommended daily intake of fat and cholesterol was no more than 40 g/day and 200 mg/day, respectively. Significant increases in estimated VO2max and total cholesterol/high density lipoprotein (HDL) and a significant decrease in serum triglycerides were documented after training. Significant differences in serum cholesterol and triglycerides between the nondiuretic and diuretic patients were also noted. No significant changes were found in low density lipoprotein (LDL), HDL, or body weight. Vigorous aerobic training and diet modification can favorably modify the deleterious effects of diuretic medications on serum triglycerides and total cholesterol/HDL in patients with documented CAD.     

Influence of 4 weeks' intervention by exercise and diet on low-density lipoprotein subfractions in obese men with type 2 diabetes.

Insulin resistance is associated with dyslipoproteinemia characterized by increased serum triglycerides, reduced high-density lipoprotein 2 (HDL2) cholesterol, and increased small, dense low-density lipoprotein (LDL) subfraction particles. Physical activity and weight reduction are known to improve insulin resistance and dyslipoproteinemia, but their influence on LDL subfractions in diabetic patients is unknown. Therefore, we investigated the effect of a 4-week intervention program of exercise (2,200 kcal/wk) and diet (1,000 kcal/d: 50% carbohydrate, 25% protein, and 25% fat; polyunsaturated/saturated fat ratio, 1.0) on glycemic control and HDL and LDL subfractions in 34 obese patients with non-insulin-dependent diabetes (age, 49 +/- 9 years; body mass index [BMI], 33.1 +/- 5.1 kg/m2). Reductions in body weight (P < .001) and improvements in fasting blood glucose, insulin, fructosamine (P < .001), and free fatty acids (P < .01) by intervention were associated with reductions in serum cholesterol and apolipoprotein B (apo B) concentrations in very-low-density lipoprotein (VLDL) (P < .01), intermediate-density lipoprotein (IDL), and small, dense (>1.040 g/mL) LDL particles (P < .001). These data underlie the positive influence of weight reduction induced by exercise and diet on insulin resistance and lipoprotein metabolism in obese diabetic patients, particularly showing improvements of the LDL subfraction profile with a decrease of small, dense LDL particles. This is of particular importance, as these particles have been shown to be associated with coronary artery disease.     

Efficacy and safety of ezetimibe added to ongoing statin therapy for treatment of patients with primary hypercholesterolemia

Ezetimibe is a lipid-lowering drug that inhibits the intestinal absorption of dietary and biliary cholesterol by blocking passage across the intestinal wall. The efficacy and safety of adding ezetimibe to ongoing statin therapy in patients with primary hypercholesterolemia was evaluated in a randomized, double-blind, placebo-controlled study. The study group included 769 adults (aged > or =18 years) with primary hypercholesterolemia who had not achieved National Cholesterol Education Program (NCEP) Adult Treatment Panel II goals with dietary alteration and statin monotherapy. Patients receiving a stable dose of a statin for > or =6 weeks were randomized to receive concurrent treatment with placebo (n = 390) or ezetimibe (n = 379), 10 mg/day, in addition to continuing their open-label statin for 8 weeks. The primary efficacy variable was the percent change in low-density lipoprotein (LDL) cholesterol from baseline with statin monotherapy to end point after intervention (secondary variables: high-density lipoprotein [HDL] cholesterol and triglycerides). Ongoing statin therapy plus ezetimibe led to changes of -25.1% for LDL cholesterol (HDL cholesterol +2.7%; triglycerides -14.0%) compared with LDL cholesterol -3.7% (p <0.001), HDL cholesterol +1.0% (p <0.05), and triglycerides -2.9% (p <0.001) for placebo added to ongoing statin therapy. Among patients not at LDL cholesterol goal at on-statin baseline, 71.5% receiving statin plus ezetimibe versus 18.9% receiving statin plus placebo reached goal at end point (odds ratio 23.7; p <0.001). The co-administration of statin and ezetimibe was generally well tolerated. Adding ezetimibe to ongoing statin therapy led to substantial additional reduction in LDL cholesterol levels, facilitating attainment of NCEP goals. Ezetimibe offers a new therapeutic option for patients receiving statins who require further reduction in LDL cholesterol.     

Effects of phytosterol ester-enriched margarine on plasma lipoproteins in mild to moderate hypercholesterolemia are related to basal cholesterol and fat intake

Dietary phytosterols have been reported to lower total and low-density lipoprotein (LDL) cholesterol. However, less is known about the influence of cholesterol and fat intake on the cholesterol-lowering effect of esterified phytosterols in mild to moderate hypercholesterolemia. Sixty-three healthy subjects (38 women, 25 men, 42 +/- 11 years, LDL cholesterol > 130 mg/dL) were investigated in a randomized, double-blind, placebo-controlled, cross-over study. A total of 20 g/d of a phytosterol ester-enriched margarine (1.82 g/d of phytosterols) was compared with a control margarine (0.06 g/d of phytosterols). After 3 weeks of intake, participants crossed over to the other margarine. A 3-day dietary recall was performed at the beginning and at the end of the study to assess cholesterol, fat, and energy intake. Phytosterol ester-enriched margarine significantly changed total cholesterol (-3.4%, P <.005), LDL cholesterol (-5.4%, P <.001, 144 +/- 28 v 154 +/- 26 mg/dL), high-density lipoprotein (HDL) cholesterol (+3.4%, P <.05), apolipoprotein B (-4.0%, P <.005), and LDL/HDL cholesterol ratio (-7.8%, P <.001) compared with the control margarine. In the tertiles with the highest dietary intake of cholesterol, energy, total fat, and saturated fatty acids, and with the highest baseline proportion of campesterol to cholesterol, LDL cholesterol reduction was 11.6% (P <.001), 9.5% (P =.001), 9.4% (P =.001), 8.4% (P =.005), and 6.2% (P =.014), respectively. Triglycerides, plasma viscosity, and fibrinogen concentration did not change significantly. The improvements of LDL, HDL, total cholesterol, apolipoprotein B concentrations, and LDL/HDL cholesterol ratio during the daily consumption of a phytosterol ester-enriched margarine were most marked in those subjects with a high dietary intake of cholesterol, energy, total fat, and saturated fatty acids and with high baseline cholesterol absorption.     

Effect of egg yolk feeding on the concentration and composition of serum lipoproteins in man

The effect of egg yolk consumption on the composition of LDL and on the concentration of HDL subclasses was studied in healthy subjects. Six volunteers consumed a diet low in cholesterol for 10 days and then daily added 6 egg yolks to their diet for another 10 days; the experiment was repeated 1 year later with the same subjects. Egg yolk consumption caused the cholesterol intake to increase by 1600 mg/day, and the fat intake by 7 energy % at the expense of carbohydrates; this increase was due almost exclusively to monounsaturated fatty acids. Upon egg yolk feeding the mean level of serum total cholesterol rose by 13%; the bulk of this rise was due to LDL cholesterol, which increased by 21%. VLDL and IDL cholesterol decreased by 19 and 11%, and serum total triglycerides by 17%. Marked relative increases of 35 and 36% were seen in the cholesterol level of the HDL subfractions with densities of 1.055-1.075 g/ml (HDL1) and 1.075-1.100 g/ml (HDL2), respectively. The HDL2/LDL cholesterol ratio increased by 16%. No change in cholesterol in HDL3 (d greater than 1.100 g/ml) was observed. The increase in cholesterol in HDL isolated by density gradient ultracentrifugation significantly exceeded the increase in cholesterol in heparin-Mn2+ soluble HDL. This suggests the formation of apo E-containing HDL, i.e. HDLc, which has HDL density but is not soluble in heparin-Mn2+. The composition of the LDL particles was significantly altered; the core became enriched in esterified cholesterol at the expense of triglycerides, and the ratio of core components to surface components increased by 7%.     

Differential effects of continuous versus intermittent administration of growth hormone to hypophysectomized female rats on serum lipoproteins and their apoproteins

The effects of the plasma pattern of GH on serum and lipoprotein levels of total cholesterol, triglycerides, apolipoprotein A-I (apo A-I), apolipoprotein B 48/100 (apo B), and apolipoprotein E (apo E) were studied in hypophysectomized female Sprague-Dawley rats, which had been given replacement therapy with L-T4 and hydrocortisone. Bovine GH (1 mg/kg.day) was administered sc either continuously by means of osmotic minipumps or by two daily injections. Serum lipoproteins were separated by sequential ultracentrifugation into very low density lipoproteins [density (d) less than 1.006 g/ml], low density lipoproteins (LDL; d 1.006-1.063 g/ml) and high density lipoproteins (HDL; d 1.063-1.21 g/ml). The content of total cholesterol and triglycerides were then determined. Apo A-I, apo B, and apo E were isolated from rat serum and antibodies raised in rabbits. In serum and in lipoprotein fractions, the content of apo A-I, apo-B, and apo E were determined by electroimmunoassay. After hypophysectomy, there occurred a decrease in serum cholesterol and serum levels of apo A-I and apo E, in spite of replacement therapy with T4 and cortisone. Similar changes were also observed in HDL. In contrast, apo B, cholesterol, and triglycerides were increased in LDL. Estradiol treatment had no effect on these changes. Continuous infusion of GH resulted in an increase in cholesterol and apo E in serum and HDL to the levels of intact females. In contrast, GH given twice daily had no effect. Therefore, the sexually dimorphic secretion of GH may be important for the regulation of sex differences in apo E and HDL cholesterol levels. There were no consistent effects of GH treatment on the levels of apo A-I in serum or HDL, but GH treatment resulted in a decrease in apo B and triglycerides in both serum and LDL, regardless of the mode of administration. This suggests that GH regulates the serum and LDL levels of apo B and triglycerides independently of the secretory pattern.     

Effects of a low-fat diet on plasma lipoprotein levels

Lowering the intake of fat to decrease serum cholesterol levels has unknown effects on the proportion of cholesterol in low-density lipoprotein (LDL) and high-density lipoprotein (HDL). Twenty normolipidemic nonvegetarians were given dietary instruction and supervision in a low-fat, semivegetarian diet for three months. Mean consumption of total fat, saturated fat, and cholesterol decreased, whereas intake of carbohydrate increased significantly on a low-fat diet. Plasma LDL levels decreased by 18% and HDL levels by 7% from prestudy baseline levels. The LDL/HDL ratio declined by 11%. Plasma triglyceride levels and body weight were unchanged. In individual subjects, the decrements in consumption of saturated fat and the increments in ingestion of polyunsaturated fat were each significantly correlated with decreases in LDL. One year after the subjects had returned to a self-selected diet, levels of dietary saturated fat and cholesterol and the plasma LDL/HDL ratio remained significantly below prestudy levels. This study and others suggest that a low-fat, high-carbohydrate diet favorably affects the plasma LDL/HDL proportion by decreasing LDL on a percentage basis 2 1/2 to three times more than it decreases HDL.     

Gemfibrozil therapy in primary type II hyperlipoproteinemia: effects on lipids, lipoproteins and apolipoproteins

Gemfibrozil lowers triglycerides, low density lipoprotein (LDL) and very low density lipoprotein (VLDL) cholesterol. It also promotes a significant increase of high density lipoprotein (HDL) cholesterol. It has been established that normalization of apolipoproteins is an important protective factor against atherosclerosis. The present report examines the effectiveness of 12 months of gemfibrozil treatment on plasma lipids and apolipoproteins in types IIa (VLDL 18 +/- 2 mg cholesterol/dL) and IIb (VLDL 58 +/- 7 mg cholesterol/dL) hypercholesterolemic patients. Gemfibrozil lowered plasma triglycerides, VLDL cholesterol and apolipoprotein B (apoB), increased HDL cholesterol and apoAI levels in both groups, and induced a very substantial reduction in LDL cholesterol in type IIa patients only. Even though HDL particles were enriched in cholesterol, indicating improvement in the reverse cholesterol transport and lower risk of atherosclerosis in both groups, it is important to note that production of cholesterol-poor LDL particles and reduction in LDL cholesterol and the LDL/HDL cholesterol ratio were observed only in the normotriglyceride group (type IIa). Due to the initially elevated concentration of plasma triglycerides and VLDL in type IIb patients and the increased catabolism of VLDL to LDL during gemfibrozil therapy, this drug has a more efficient regulating effect on LDL particles in type IIa compared with type IIb hyperlipidemia.     

Clinical results with gemfibrozil

Gemfibrozil has been found to increase high-density lipoprotein (HDL) cholesterol levels in both animal and clinical studies. Although a reduction in saturated fat intake and a concurrent increase in unsaturated fat intake may reduce low-density lipoprotein (LDL) cholesterol values, the only dietary modification known to increase HDL is that resulting from significant weight loss. The framingham study showed that the risk associated with HDL cholesterol (lower values, higher risk) is independent of the risk relative to LDL cholesterol (higher values, higher risk).A multicenter trial in the United States showed a reduction of elevated serum triglyceride levels by more than 40% and of cholesterol to normal or by 20% in 50% of patients who received gemfibrozil, versus 25% of those who received a placebo. Gemfibrozil therapy reduced elevated serum very low density lipoprotein levels concurrently with triglyceride levels. It also increased serum HDL by approximately 20% and the $\text{HDL}\text{total cholesterol}$ ratio by approximately 30%. HDL cholesterol levels continued to increase for up to 2 years in the multicenter study. The increase over baseline levels was seen in all 3 types of hyperlipoproteinemia (IIA, IIB and IV).The most common side effects were minor gastrointestinal symptoms and transient abnormalities in hepatic enzymes, which occurred in less than 3% of the patients. There were no other liver function abnormalities and no evidence that gemfibrozil induced liver toxicity. Gemfibrozil had a safety advantage over clofibrate, especially with regard to lithogenic potential. Gemfibrozil demonstrated a low side-effect profile and a positive influence on regulating lipoprotein levels in patients with hypercholesterolemia and hypertriglyceridemia.     

Quantitative and qualitative serum lipoprotein analysis. Part 1. Studies in healthy men and women.

Preparative ultracentrifugal and electrophoretic analysis of serum lipoproteins was performed in 30-70-year-old healthy, fasting males (N = 80) and females (N = 77), randomly selected from the Uppsala region, Sweden. The concentrations of cholesterol and triglycerides in total serum and in VLDL,LDL and HDL lipoprotein classes are reported. Total serum, VLDL and LDL triglycerides and cholesterol concentrations increased with age, while HDL cholesterol and triglyceride concentrations did not vary with age. Overweight persons had higher total serum triglyceride, higher VLDL cholesterol and triglyceride and lower HDL cholesterol levels. The upper 90% population limit values for non-overweight males/females were: total triglycerides (mmol/l) 2.5/2.0, total cholesterol (mg/100 ml) 298/300, VLDL triglyceride 1.80/1.05, VLDL-cholesterol 32/33, LDL triglyceride 0.69/0.69, LDL cholesterol 210/218, HDL triglyceride 0.32/0.34 and HDL-cholesterol 69/93. The 2 major differences between males and females were that females had lower VLDL but higher HDL concentrations. For VLDL there was a very strong and for LDL a moderately strong positive correlation between cholesterol and triglyceride contents. In HDL however, the mearsured amounts of cholesterol and triglycerides did not correlate at all. Sinking pre-beta lipoproteins was found in about 25% of cases and a second pre-beta band floating at d 1.006, late pre-beta, was found in 35% of male and 25% of female subjects. Subjects with sinking pre-beta lipoprotein did not differ from other subjects with regard to the concentration of cholesterol and triglycerides in the 3 lipoprotein classes. Males, but not females, with the late pre-beta (LPB), had an increased amount of cholesterol in VLDL and a raised cholesterol-triglyceride ratio in this lipoprotein class. Also the LDL triglyceride level was increased in males with the late pre-beta lipoprotein.     

Cholesterol reduction by different plant stanol mixtures and with variable fat intake.

Our aim was to investigate (1) whether different campestanol/sitostanol mixtures in margarine differ in reducing serum cholesterol, and (2) whether sitostanol ester in butter decreases serum cholesterol and alters cholesterol absorption and metabolism. Twenty-three postmenopausal women replaced 25 g dietary fat with (1) sitostanol ester-rich (campestanol to sitostanol ratio 1:11) and (2) campestanol ester-rich (campestanol to sitostanol ratio 1:2) rapeseed oil margarine, (3) butter, and (4) sitostanol ester-rich (campestanol to sitostanol ratio 1:13) butter. The respective scheduled stanol intake was 3.18, 3.16, and 2.43 g/d. The 6-week margarine periods and, after an 8-week washout, 5-week butter periods were double-blind and in random order. Serum cholesterol precursor sterols (indicators of cholesterol synthesis) and plant sterols (indicators of cholesterol absorption) were quantified with gas-liquid chromatography (GLC). Low-density lipoprotein (LDL) cholesterol was reduced by 8% and 10% with the sitostanol and campestanol ester-rich margarines versus baseline (P < .05 for both) and high-density lipoprotein (HDL) cholesterol was increased by 6% and 5% (P < .05), so the LDL/HDL cholesterol ratio was reduced by 15% (P < .05 for both). Sitostanol ester-rich butter decreased LDL cholesterol 12% and the LDL/HDL cholesterol ratio 11% (P < .05 for both) versus the butter period. The serum proportions of plant sterols and cholestanol were similarly reduced and those of cholesterol precursor sterols were similarly increased during all periods (P < .05 for all). Serum proportions of sitostanol and campestanol were slightly increased, indicating that their absorption related to their dietary intake. During all stanol interventions, serum vitamin D and retinol concentrations and alpha-tocopherol to cholesterol ratios were unchanged, whereas those of alpha- and beta-carotenes were significantly reduced. We conclude that varying the campestanol to sitostanol ratio from 1:13 to 1:2 in margarine and in butter similarly decreased cholesterol absorption, LDL cholesterol, and the LDL/HDL cholesterol ratio such that the serum lipids became less atherogenic.     

Treatment of type III hyperlipoproteinemia with four different treatment regimens

The efficacy of clofibrate (CPIB) and nicotinic acid (NA) in the treatment of type III hyperlipoproteinemia was evaluated in 5 male subjects in a randomized cross-over study with clofibrate 1 g b.i.d. and NA 3 g/day (given either b.i.d. or t.i.d.). Following a baseline period of 6 weeks, each drug was given for 12 weeks with samples for lipid and lipoprotein determinations obtained at 6, 9, and 12 weeks. Both clofibrate and NA resulted in a significant reduction from baseline of total cholesterol (23% and 28%), VLDL cholesterol (49% and 56%), total triglycerides (40% and 43%), and VLDL triglycerides (46% and 48%), as well as a significant increase in HDL cholesterol (22% and 28%) and HDL/LDL ratio (31% and 62%). The HDL/LDL ratio was higher on NA than clofibrate (0.47 +/- 0.19 vs. 0.38 +/- 0.09, P less than 0.05). Four subjects were continued in the study and treated sequentially with NA 3.0 g/day (alternate to the previous schedule) and gemfibrozil 1.2 g/d in divided doses. Each of the 4 regimens resulted in a significant change from baseline of each of the measured lipid and lipoprotein determinations except LDL cholesterol. Comparison among the treatment regimens revealed no differences except for significantly higher HDL cholesterol and HDL/LDL ratio with NA given t.i.d.     

The effect on serum lipids and oxidized low-density lipoprotein of supplementing self-selected low-fat diets with soluble-fiber, soy, and vegetable protein foods

An increased intake of soluble fiber and soy protein may improve the blood lipid profile. To assess any additional benefit on serum lipids of providing soy protein and soluble-fiber foods to hyperlipidemic subjects already consuming low-fat, low-cholesterol therapeutic diets, 20 hyperlipidemic men and postmenopausal women completed 8-week test and control dietary treatments in a randomized crossover design as part of an ad libitum National Cholesterol Education Program (NCEP) step 2 therapeutic diet (<7% saturated fat and <200 mg/d cholesterol). During the test phase, foods high in soy, other vegetable proteins, and soluble fiber were provided. During the control phase, low-fat dairy and low-soluble-fiber foods were provided. Fasting blood lipid and apolipoprotein levels were measured at 4 and 8 weeks of each phase. On the test diet, 12 +/- 2 g/d soy protein was selected from the foods chosen. Direct comparison of test and control treatments indicated an elevated high-density lipoprotein (HDL) cholesterol concentration on the test diet (6.4% +/- 2.4%, P = .013) and a significantly reduced total to HDL cholesterol ratio (-5.9% +/- 2.3%, P = .020). The proportion of conjugated dienes in the low-density lipoprotein (LDL) cholesterol fraction was significantly reduced (8.5% +/- 3.3%, P = .020) as a marker of oxidized LDL. A combination of acceptable amounts of soy, vegetable protein, and soluble-fiber foods as part of a conventional low-fat, low-cholesterol therapeutic diet is effective in further reducing serum lipid risk factors for cardiovascular disease.     

Double-blind, placebo-controlled, cross-over trial of probucol in heterozygous familial hypercholesterolaemia

Ten patients with heterozygous familial hypercholesterolaemia (FH) were given probucol 500 mg b.d. or placebo for 3 months in a randomised order in a double-blind cross-over trial. There was a 14% decrease in serum cholesterol concentration due to a reduction in both low density lipoprotein (LDL) cholesterol and high density lipoprotein (HDL) cholesterol. The subfraction of HDL most affected was HDL2. Reductions in serum LDL cholesterol concentration exceeding 20% were obtained in 3 (30%) of the patients. The magnitude of the change in LDL cholesterol concentration was related to the level of serum HDL2 cholesterol without therapy and to the magnitude of its decrease on probucol. Intravenous intralipid tolerance was unaffected by probucol administration. Serum apolipoprotein B concentration decreased less with probucol than did that of serum LDL cholesterol.     

Effects of soybean protein and very low dietary cholesterol on serum lipids, biliary lipids, and fecal sterols in humans

Soy-base texturized vegetable protein (TVP; Archer Daniels Midland, Decatur, IL) has been used to decrease serum cholesterol and as a substitute for animal protein to achieve very low levels of dietary cholesterol. The effect of very low dietary cholesterol and of TVP on biliary lipids and fecal sterols is unclear. The study objective was to determine the effects of very low intake of dietary cholesterol, as well as TVP itself, on serum lipids, biliary lipids, and fecal sterols. We studied eight normal subjects living on a metabolic ward during three randomly ordered 6- to 7-week periods: (1) standard cholesterol diet (190 to 550 mg/d), (2) TVP-low-cholesterol diet (17 to 30 mg/d), and (3) TVP-standard cholesterol diet. By analysis of covariance (ANCOVA), reducing dietary cholesterol to these very low levels significantly decreased serum low-density lipoprotein (LDL) cholesterol (P=.048) but did not affect high-density lipoprotein (HDL) cholesterol or triglyceride. TVP resulted in a borderline significant reduction in LDL cholesterol (P=.058) with a highly significant reduction in HDL cholesterol (P=.004) and an increase in serum triglyceride (P=.010). During TVP ingestion, there was a highly significant increase in the output of fecal neutral sterols (P=.005) and a tendency for a higher output of fecal acidic sterols (P=.100). Fecal sterol balance was significantly more negative (indicating increased cholesterol synthesis) during TVP ingestion (P=.016). Neither TVP nor the very-low-cholesterol diet appreciably affected the gallbladder bile molar percent cholesterol or saturation index. The data are consistent with the hypothesis that to the extent TVP decreases serum LDL cholesterol (an effect of borderline significance in this study), the effect occurs via a reduction in the absorption of cholesterol and perhaps bile acid. However, the potential benefit of decreasing LDL cholesterol in this way seems to be at least partially offset by a concomitant reduction in HDL cholesterol and an increase in serum triglycerides.     

上海地区中国人血脂紊乱类型与胰岛素抵抗

目的：探讨上海地区中国人脂代谢紊乱的类型与胰岛素抵抗的关系。方法：830例年龄≥40岁（男300例,女530例）正常人和血脂紊乱者,后者分为7个亚组,包括单纯低高密度脂蛋白（HDL）组（亚组Ⅰ）、单纯高甘油三酯（TG）组（亚组Ⅱ）、单纯高胆固醇（TC）或高低密度脂蛋白（LDL）组（亚组Ⅲ）、低HDL合并高TG组（亚组Ⅳ）、低HDL合并高TC或高LDL组（亚组Ⅴ）、高TG合并高TC或高LDL组（亚组Ⅵ）、低HDL合并高TG及高TC或高LDL组（亚组Ⅶ）,用稳态模式评估法（HOMA）评价胰岛素抵抗（IR）。结果：校正年龄、性别、体重指数等因素后,伴有高TG的各血脂异常 亚组的胰岛素抵抗指数升高较为明显,总体脂、腹部脂肪对血脂紊乱的影响较为显著;体脂对胰岛素抵抗指数的影响部分是通过TG介导的,结论：TG升高可作为个体存在胰岛纱抵抗的指标。     

The hypolipidemic action of probucol. Drug transport and lipoprotein composition in type IIa hyperlipoproteinemia

In this study Probucol transport and the effect of the drug on lipoprotein composition in 9 cases of type IIa hypercholesterolemia were investigated. Probucol lowered plasma cholesterol by 20%, without affecting triglycerides. HDL cholesterol was decreased and a slight reduction in LDL cholesterol was noted. This was due to a reduction in the number of circulating lipoprotein particles, without modification in the lipid/protein ratio, mainly cholesterol/protein ratio. Probucol was almost entirely removed by lipoproteins; 75% of the drug was found in LDL, the remainder being equally distributed in VLDL and HDL. There was no correlation between the serum Probucol level, or the amount of Probucol bound to lipoproteins, and the decrease in serum or lipoprotein cholesterol. However, there was a significant increase of the EC/TC (esterified cholesterol/total cholesterol) ratio in VLDL and LDL, but not in HDL.     

Clinical use of a carbohydrate-restricted diet to treat the dyslipidemia of the metabolic syndrome

Background: The metabolic syndrome is characterized by an atherogenic dyslipidemia identifiable using lipoprotein subclass analysis. This study assesses the effect of a carbohydrate-restricted diet on the dyslipidemia of the metabolic syndrome in a clinical setting. Methods: This is a retrospective chart review of patients attending a preventive medicine clinic using lipoprotein subclass analysis (by NMR spectroscopy) to identify the atherogenic dyslipidemia. If present, patients were counseled to begin a carbohydrate-restricted diet (< 20 g/day). Patients already on statin therapy were included only if the medication dose was not changed. The outcomes were changes in body weight, fasting serum lipid profiles and serum lipoprotein subclasses. Results: Of 122 patients identified, 80 patients had complete pre- and post-treatment data. The mean (+/-SD) age was 66 +/- 9 years, baseline weight was 85 +/- 12 kg, BMI was 28.1 +/- 3.6, 73% were male, 99% were Caucasian. Sixty-five percent were taking statin medication. Carbohydrate-restriction led to a 13% reduction in total cholesterol, 16% reduction in LDL cholesterol, 38% reduction in triglycerides, and a 13% increase in HDL cholesterol (all p values < 0.001). Carbohydrate-restriction also led to a reduction in LDL particle concentration of 28%, a reduction in small LDL of 82%, a reduction of large VLDL of 62%, and an increase in large HDL of 30% (all p values < 0.001). Conclusions: A carbohydrate-restricted diet recommendation led to improvements in lipid profiles and lipoprotein subclass traits of the metabolic syndrome in a clinical outpatient setting, and should be considered as a treatment for the metabolic syndrome.     

Influence of mild to moderately elevated triglycerides on low density lipoprotein subfraction concentration and composition in healthy men with low high density lipoprotein cholesterol levels

Epidemiologic studies have shown that a dyslipoproteinemia with low concentrations of high density lipoprotein (HDL) cholesterol and elevated serum triglycerides (TG) is associated with a particularly high incidence of coronary artery disease. This lipid profile is associated with increased concentrations of small, dense low density lipoprotein (LDL) particles. To evaluate the role of mild to moderately elevated TG on the LDL subfraction profile in patients with low HDL cholesterol, concentration and composition of six LDL subfractions was determined by density gradient ultracentrifugation in 41 healthy men (31+/-9 years, body mass index (BMI) 25.1+/-3.9 kg/m2) with equally low HDL cholesterol levels < 0.91 mmol/l but different TG levels: TG < 1.13 mmol/l, n = 16; TG = 1.13-2.26 mmol/l, n = 13: TG = 2.26-3.39 mmol/l, n = 12. Those men with moderately elevated TG levels between 2.26 and 3.39 mmol/l had significantly higher concentrations of very low density lipoprotein (VLDL), intermediate low density lipoprotein (IDL), and small, dense LDL apoB and cholesterol than men with TG < 1.13 mmol/l. With increasing serum TG, the TG content per particle also increased in VLDL, IDL as well as total LDL particles while the cholesterol and phospholipid (PL) content decreased in VLDL and IDL, but not in LDL particles. LDL subfraction analysis revealed that only large, more buoyant LDL particles (d < 1.044 g/ml) but not the smaller, more dense LDL, were enriched in TG. Small, dense LDL particles were depleted of free cholesterol (FC) and PL. This study has shown that in men with low HDL cholesterol levels mild to moderately elevated serum TG strongly suggest the presence of other metabolic cardiovascular risk factors and in particular of a more atherogenic LDL subfraction profile of increased concentration of small, dense LDL particles that are depleted in surface lipids.