Effects of dietary cholesterol and fat saturation on plasma lipoproteins in an ethnically diverse population of healthy young men.

The individual effects of dietary cholesterol and fat saturation on plasma lipoprotein concentrations were determined in an ethnically diverse population of normolipidemic young men (52 Caucasian, 32 non-Caucasian). The experimental diets contained approximately 200 or 600 mg/d of cholesterol, 36-38% of calories as fat, and high or low proportions of saturated and polyunsaturated fat (polyunsaturated/saturated fat ratio approximately 0.8 vs 0.3). At the lower cholesterol intake, the high saturated fat diet had only a modest effect on LDL cholesterol in Caucasians (+ 6 mg/dl-1) and none in non-Caucasians. 600 mg cholesterol with high saturated fat led to a substantial mean increase in LDL cholesterol, which was significantly greater in Caucasian than in non-Caucasian subjects (+ 31 mg/dl vs 16 mg/dl, P < 0.005). 600 mg cholesterol with increased polyunsaturated fat gave a mean LDL increase of 16 mg/dl, lower than found when the same high cholesterol intake was coupled with increased saturated fat. Variation in cholesterol rather than the proportions of saturated and polyunsaturated fat had the most influence on LDL-cholesterol levels. Among non-Caucasians it was the only significant factor.     

Individual Variation in the Effects of Dietary Cholesterol on Plasma Lipoproteins and Cellular Cholesterol Homeostasis in Man: STUDIES OF LOW DENSITY LIPOPROTEIN RECEPTOR ACTIVITY AND 3-HYDROXY-3-METHYLGLUTARYL COENZYME A REDUCTASE ACTIVITY IN BLOOD MONONUCLEAR CELLS

The effects of dietary cholesterol on plasma lipoproteins and cholesterol homeostasis in blood mononuclear cells have been examined in healthy adults. Addition of 1,500 mg of cholesterol to the daily diet of 37 subjects for 14 d was associated with a wide range of response of plasma total cholesterol concentration (from −6 to +75 mg/dl; mean change, +29 mg/dl; P < 0.001). Increases in plasma cholesterol reflected increased cholesterol concentrations in intermediate density lipoprotein (IDL; 1.006-1.019 g/ml), low density lipoprotein (LDL; 1.019-1.063 g/ml), and the HDL₂ subclass (1.063-1.125 g/ml) of high density lipoprotein, which on average accounted for 20, 58, and 22%, respectively, of the total increment. Similar responses occurred in 14 other subjects given 750 mg cholesterol per day for 28 d. Plasma apolipoprotein B concentrations in IDL and LDL also increased.     

A low-fat diet decreases high density lipoprotein (HDL) cholesterol levels by decreasing HDL apolipoprotein transport rates.

Diets that reduce atherosclerosis risk lower levels of HDL cholesterol (HDL-C), but the significance of this is unclear. To better understand the mechanism of this phenomenon we studied the turnover of HDL apolipoproteins A-I and A-II in 13 subjects on two contrasting metabolic diets. Upon changing from high to low intake of saturated fat and cholesterol the mean HDL-C decreased 29% from 56 +/- 13 (SD) to 40 +/- 10 mg/dl, while apo A-I levels fell 23% from 139 +/- 22 to 107 +/- 22 mg/dl (both P less than 0.001). Mean apo A-II levels did not change. The fractional catabolic rate (FCR) of apo A-I increased 11% from 0.228 +/- 0.048 to 0.254 +/- 0.063 pools/d, while its absolute transport rate (TR) decreased 14% from 12.0 +/- 2.7 to 10.3 +/- 3.4 mg/kg per d (both P = 0.005). The decrease in HDL-C and apo A-I levels correlated with the decrease in apo A-I TR (r = 0.79 and 0.83, respectively; P less than 0.001), but not with the increase in apo A-I FCR (r = -0.04 and -0.02, respectively). In contrast, within each diet the HDL-C and apo A-I levels were inversely correlated with apo A-I FCR both on the high-fat (r = -0.85 and -0.77, P less than 0.001 and = 0.002, respectively) and low-fat diets (r = -0.67 and -0.48, P = 0.012 and 0.098, respectively) but not with apo A-I TR. In summary, diet-induced changes in HDL-C levels correlate with and may result from changes in apo A-I TR. In contrast, differences in HDL-C levels between people on a given diet correlate with and may result from differences in apo A-I FCR. Therefore, the mechanism of dietary effects on HDL levels differs substantially from the mechanism explaining the differences in levels between individuals on a fixed diet. In assessing coronary heart disease risk, it may be inappropriate to conclude that diet-induced decreases in HDL are equivalent to low HDL within a given diet.     

Dietary fats do not contribute to hyperlipidemia in children and adolescents with type 1 diabetes

OBJECTIVE: To determine the relative influence of diet, metabolic control, and familial factors on lipids in children with type 1 diabetes and control subjects. RESEARCH DESIGN AND METHODS: We assessed fasting serum cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, lipoprotein(a), apolipoprotein (apo)-A1, and apoB in 79 children and adolescents with type 1 diabetes and 61 age- and sex-matched control subjects, together with dietary intakes using a quantitative food frequency questionnaire. RESULTS: Total cholesterol, LDL cholesterol, apoB, HDL cholesterol, and apoA1 were significantly higher in children with diabetes. Children with diabetes had higher percentage energy intake from complex carbohydrates (P = 0.001) and fiber intake (P = 0.02), and they had lower intake of refined sugar (P < 0.001) and percentage energy from saturated fat (P = 0.045) than control subjects. Total cholesterol (beta = 0.43, P < 0.001), LDL cholesterol (beta = 0.4, P < 0.001), and apoB (beta = 0.32, P = 0.006) correlated independently with HbA(1c) but not dietary intake. HDL cholesterol (beta = 0.24, P = 0.05) and apoA1 (beta = 0.32, P = 0.004) correlated independently with HbA(1c), and HDL cholesterol (beta = -0.34, P = 0.009) correlated with percentage energy intake from complex carbohydrates. Triglycerides correlated independently with percentage energy intake from complex carbohydrates (beta = 0.33, P = 0.01) and insulin dose (beta = 0.26, P = 0.04). Subjects with diabetes and elevated LDL (>3.35 mmol/l, >130 mg/dl), for whom dietary therapy would be recommended, had significantly higher HbA(1c) (P = 0.007), but they had higher intake of complex carbohydrates than subjects with LDL cholesterol <3.35 mmol/l. CONCLUSIONS: Lipid abnormalities remain common in children and adolescents with type 1 diabetes who adhere to current dietary recommendations, and they relate to metabolic control but not dietary intake.     

Massive xanthomatosis and atherosclerosis in cholesterol-fed low density lipoprotein receptor-negative mice.

Mice that are homozygous for a targeted disruption of the LDL receptor gene (LDLR-/- mice) were fed a diet that contained 1.25% cholesterol, 7.5% cocoa butter, 7.5% casein, and 0.5% cholic acid. The total plasma cholesterol rose from 246 to > 1,500 mg/dl, associated with a marked increase in VLDL, intermediate density lipoproteins (IDL), and LDL cholesterol, and a decrease in HDL cholesterol. In wild type littermates fed the same diet, the total plasma cholesterol remained < 160 mg/dl. After 7 mo, the LDLR-/- mice developed massive xanthomatous infiltration of the skin and subcutaneous tissue. The aorta and coronary ostia exhibited gross atheromata, and the aortic valve leaflets were thickened by cholesterol-laden macrophages. No such changes were seen in the LDLR-/- mice on a normal chow diet, nor in wild type mice that were fed either a chow diet or the high-fat diet. We conclude that LDL receptors are largely responsible for the resistance of wild type mice to atherosclerosis. The cholesterol-fed LDLR-/- mice offer a new model for the study of environmental and genetic factors that modify the processes of atherosclerosis and xanthomatosis.     

Effect of digestible carbohydrates on glucose control in insulin-dependent diabetic patients

Recent studies have demonstrated that high-carbohydrate-high-fiber diets may improve the metabolic control in diabetes. To evaluate the influence of dietary carbohydrates separate from dietary fiber on blood glucose control, six insulin-dependent diabetic patients (IDD) were assigned in random order to two weight-maintaining diets for consecutive periods of 10 days. The diets differed in carbohydrate (41% in diet A and 60% in diet B) and fat content (41% and 20%, respectively) but were identical in calories, proteins, simple sugars, and fiber. After each dietary period blood glucose was continuously monitored for 24 h (Biostator GCIIS, Life Science Instruments, Miles Laboratories, Elkhart, Indiana). The M value was 48 +/- 20 after diet A and 96 +/- 27 after diet B (t = 3.83, P less than 0.025); the mean daily blood glucose was 152 +/- 5 mg/dl after diet A and 206 +/- 11 mg/dl after diet B (t = 7.50, P less than 0.001). Similarly, the blood glucose level for the 3-h period after each of the three main meals was lower after diet A than after diet B (analysis of variance: F = 5.2, P less than 0.05). No significant difference in fasting serum cholesterol, triglycerides, or serum lipoprotein composition was observed between the two diets. In order to separate the influence of dietary carbohydrate and fat on postprandial blood glucose concentration, an additional test meal experiment was performed in eight insulin-dependent diabetic patients. In random order on consecutive days they were given two standard meals that were identical in carbohydrate and protein content and differed only in the amount of olive oil added to the meals (12 g versus 36 g).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of replacing saturated fat with complex carbohydrate in diets of subjects with NIDDM

This study examined the safety of an isocaloric high-complex carbohydrate low-saturated fat diet (HICARB) in obese patients with non-insulin-dependent diabetes mellitus (NIDDM). Although hypocaloric diets should be recommended to these patients, many find compliance with this diet difficult; therefore, the safety of an isocaloric increase in dietary carbohydrate needs assessment. Lipoprotein cholesterol and triglyceride (TG, mg/dl) concentrations in isocaloric high-fat and HICARB diets were compared in 7 NIDDM subjects (fat 32 +/- 3%, fasting glucose 190 +/- 38 mg/dl) and 6 nondiabetic subjects (fat 33 +/- 5%). They ate a high-fat diet (43% carbohydrate; 42% fat, polyunsaturated to saturated 0.3; fiber 9 g/1000 kcal; cholesterol 550 mg/day) for 7-10 days. Control subjects (3 NIDDM, 3 nondiabetic) continued this diet for 5 wk. The 13 subjects changed to a HICARB diet (65% carbohydrate; 21% fat, polyunsaturated to saturated 1.2; fiber 18 g/1000 kcal; cholesterol 550 mg/day) for 5 wk. NIDDM subjects on the HICARB diet had decreased low-density lipoprotein cholesterol (LDL-chol) concentrations (107 vs. 82, P less than .001), but their high-density lipoprotein cholesterol (HDL-chol) concentrations, glucose, and body weight were unchanged. Changes in total plasma TG concentrations in NIDDM subjects were heterogeneous. Concentrations were either unchanged or had decreased in 5 and increased in 2 NIDDM subjects. Nondiabetic subjects on the HICARB diet had decreased LDL-chol (111 vs. 81, P less than .01) and unchanged HDL-chol and plasma TG concentrations).(ABSTRACT TRUNCATED AT 250 WORDS)     

A comparison of lipid and glycemic effects of pioglitazone and rosiglitazone in patients with type 2 diabetes and dyslipidemia

OBJECTIVE: Published reports suggest that pioglitazone and rosiglitazone have different effects on lipids in patients with type 2 diabetes. However, these previous studies were either retrospective chart reviews or clinical trials not rigorously controlled for concomitant glucose- and lipid-lowering therapies. This study examines the lipid and glycemic effects of pioglitazone and rosiglitazone. RESEARCH DESIGN AND METHODS: We enrolled subjects with a diagnosis of type 2 diabetes (treated with diet alone or oral monotherapy) and dyslipidemia (not treated with any lipid-lowering agents). After a 4-week placebo washout period, subjects randomly assigned to the pioglitazone arm (n = 400) were treated with 30 mg once daily for 12 weeks followed by 45 mg once daily for an additional 12 weeks, whereas subjects randomly assigned to rosiglitazone (n = 402) were treated with 4 mg once daily followed by 4 mg twice daily for the same intervals. RESULTS: Triglyceride levels were reduced by 51.9 +/- 7.8 mg/dl with pioglitazone, but were increased by 13.1 +/- 7.8 mg/dl with rosiglitazone (P < 0.001 between treatments). Additionally, the increase in HDL cholesterol was greater (5.2 +/- 0.5 vs. 2.4 +/- 0.5 mg/dl; P < 0.001) and the increase in LDL cholesterol was less (12.3 +/- 1.6 vs. 21.3 +/- 1.6 mg/dl; P < 0.001) for pioglitazone compared with rosiglitazone, respectively. LDL particle concentration was reduced with pioglitazone and increased with rosiglitazone (P < 0.001). LDL particle size increased more with pioglitazone (P = 0.005). CONCLUSIONS: Pioglitazone and rosiglitazone have significantly different effects on plasma lipids independent of glycemic control or concomitant lipid-lowering or other antihyperglycemic therapy. Pioglitazone compared with rosiglitazone is associated with significant improvements in triglycerides, HDL cholesterol, LDL particle concentration, and LDL particle size.     

Beneficial effects of a Dietary Approaches to Stop Hypertension eating plan on features of the metabolic syndrome

OBJECTIVE: To determine the effects of a Dietary Approaches to Stop Hypertension (DASH) eating plan on metabolic risks in patients with the metabolic syndrome. RESEARCH DESIGN AND METHODS: This was a randomized controlled outpatient trial conducted on 116 patients with the metabolic syndrome. Three diets were prescribed for 6 months: a control diet, a weight-reducing diet emphasizing healthy food choices, and the DASH diet with reduced calories and increased consumption of fruit, vegetables, low-fat dairy, and whole grains and lower in saturated fat, total fat, and cholesterol and restricted to 2,400 mg Na. The main outcome measures were the components of the metabolic syndrome. RESULTS: Relative to the control diet, the DASH diet resulted in higher HDL cholesterol (7 and 10 mg/dl), lower triglycerides (-18 and -14 mg/dl), systolic blood pressure (SBP) (-12 and -11 mmHg), diastolic blood pressure (-6 and -7 mmHg), weight (-16 and -14 kg), fasting blood glucose (FBG) (-15 and -8 mg/dl), and weight (-16 and -15 kg), among men and women, respectively (all P < 0.001). The net reduction in triglycerides (-17 and -18 mg/dl), SBP (-11 and -11 mmHg), diastolic blood pressure (-5 and -6 mmHg), and FBG (-4 and -6 mg/dl), weight (-16 and -15 kg), and increase in HDL (5 and 10 mg/dl) among men and women, respectively, was higher in the DASH group (all P < 0.05). The weight-reducing diet resulted in significant change in triglycerides (-13 and -10 mg/dl), SBP (-6 and -6 mmHg), and weight (-13 and -12 kg) among men and women, respectively (all P < 0.05). CONCLUSIONS: The DASH diet can likely reduce most of the metabolic risks in both men and women; the related mechanisms need further study.     

High protein diet complements resin therapy of familial hypercholesterolemia.

The intermediate-term effects on plasma lipoprotein lipids of substituting meat and dairy protein for carbohydrate in the diets of five subjects (three women, two men) with familial hypercholesterolemia receiving cholestyramine (mean dose, 18 g/d) were studied. Subjects were randomly allocated to either the high or low protein diets (mean 27 versus 10% of energy as protein, 25% as fat, and 48 versus 65% as carbohydrate) for 4 to 5 weeks and then switched to the other diet for another 4 to 5 weeks. Mean fasting plasma HDL cholesterol rose significantly by 17 +/- 3% (1.11 +/- 0.12 vs 0.95 +/- 0.11 mmol/L, p less than 0.005, n = 5), whereas total triglycerides fell by 23 +/- 2% (1.7 +/- 0.3 vs 2.2 +/- 0.3 mmol/L, p less than 0.005, n = 5), VLDL triglycerides fell by 28 +/- 5% (0.88 +/- 0.15 vs 1.18 +/- 0.19 mmol/L, p less than 0.02, n = 5), VLDL cholesterol fell by 32 +/- 7% (0.39 +/- 0.08 vs 0.56 +/- 0.09 mmol/L, p less than 0.01, n = 5), the ratio of LDL cholesterol: HDL cholesterol by 19 +/- 5% (4.7 +/- 0.7 vs 5.7 +/- 0.7, p less than 0.05) and that of total cholesterol: HDL cholesterol by 16 +/- 5% (6.6 +/- 0.5 vs 8.0 +/- 0.7, p less than 0.05) on the high versus low protein diet. Increasing dietary protein intake at the expense of carbohydrate may be useful in treating hypoalphalipoproteinemia and/or hypertriglyceridemia in patients with familial hypercholesterolemia.     

Favorable effects of pioglitazone and metformin compared with gliclazide on lipoprotein subfractions in overweight patients with early type 2 diabetes

OBJECTIVE: To compare effects of different oral hypoglycemic drugs as first-line therapy on lipoprotein subfractions in type 2 diabetes. RESEARCH DESIGN AND METHODS: Sixty overweight type 2 diabetic patients not on lipid-lowering therapy were randomized to metformin, pioglitazone, or gliclazide after a 3-month dietary run-in. Drug doses were uptitrated for 3 months to optimize glycemia and were kept fixed for a further 3 months. LDL subfractions (LDL(1), LDL(2), and LDL(3)) were prepared by density gradient ultracentrifugation at randomization and study end. Triglycerides, cholesterol, total protein, and phospholipids were measured and mass of subfractions calculated. HDL subfractions were prepared by precipitation. The primary end point was change in proportion of LDL as LDL(3). RESULTS: HbA(1c), triglycerides, glucose, and cholesterol were comparable across groups at baseline and over time. LDL(3) mass and the LDL(3)-to-LDL ratio fell with pioglitazone (LDL(3) mass 36.2 to 28.0 mg/dl, P < 0.01; LDL(3)-to-LDL 19.2:13.3%, P < 0.01) and metformin (42.7 to 31.5 mg/dl, P < 0.01; 21.3:16.2%, P < 0.01, respectively) with no change on gliclazide. LDL(3) reductions were associated with reciprocal LDL(1) increases. Changes were independent of BMI, glycemic control, and triglycerides. Total HDL cholesterol increased on pioglitazone (1.28 to 1.36 mmol/l, P = 0.02) but not gliclazide (1.39 to 1.37 mmol/l, P = NS) or metformin (1.26 to 1.18 mmol/l, P = NS), largely due to an HDL(2) increase (0.3 to 0.4 mmol/l, P < 0.05). HDL(3) cholesterol fell on metformin (0.9 to 0.85 mmol/l, P < 0.01). On pioglitazone and metformin, the HDL(2)-to-HDL(3) ratio increased compared with no change on gliclazide. CONCLUSIONS: For the same improvement in glycemic control, pioglitazone and metformin produce favorable changes in HDL and LDL subfractions compared with gliclazide in overweight type 2 diabetic patients. Such changes may be associated with reduced atherosclerosis risk and may inform the choice of initial oral hypoglycemic agent.     

Effect of energy restriction, weight loss, and diet composition on plasma lipids and glucose in patients with type 2 diabetes.

OBJECTIVE: To determine the optimal diet for improving glucose and lipid profiles in obese patients with type 2 diabetes during moderate energy restriction. RESEARCH DESIGN AND METHODS: A total of 35 free-living obese patients with type 2 diabetes were assigned to one of three 1,600 kcal/day diets for 12 weeks. The diets were high carbohydrate (10% fat, 4% saturated), high monounsaturated fat (MUFA) (32% fat, 7% saturated), or high saturated fat (SFA) (32% fat, 17% saturated). RESULTS: Diet composition did not affect the magnitude of weight loss, with subjects losing an average of 6.6 +/- 0.9 kg. Energy restriction and weight loss resulted in reductions in fasting plasma glucose (-14%), insulin (-27%), GHb (-14%), and systolic (-7%) and diastolic blood pressure (-10%) levels and the glucose response area (-17%) independent of diet composition. Diet composition did affect the lipoprotein profile. LDL was 10% and 17% lower with the high-carbohydrate and high-MUFA diets, respectively, whereas no change was observed with the high-SFA diet (P < 0.001 for effect of diet). HDL was transiently reduced on the high-carbohydrate diet at weeks 1, 4, and 8, whereas higher fat consumption maintained these levels. The total cholesterol:HDL ratio, although significantly reduced on the high-MUFA diet (P < 0.01), was not different from the other two diets after adjustment for baseline differences. CONCLUSIONS: Energy restriction, independent of diet composition, improves glycemic control; however, reducing SFA intake by replacing SFA with carbohydrate or MUFA reduces LDL maximally during weight loss and to a greater degree than has been shown in weight-stable studies.     

Direct adsorption of lipoproteins (DALI) from whole blood: first long-term clinical experience with a new LDL-apheresis system for the treatment of familial hypercholesterolaemia

BACKGROUND: The DALI (direct adsorption of lipoproteins) LDL-apheresis system is a novel device for the removal of lipoproteins from whole blood. METHODS: We report the first long-term treatment experience (16.7 +/- 12.6 months; 57 +/- 43 treatments/patient) using different DALI adsorber sizes (DALI-500, DALI-750, DALI-1000) in seven patients with homozygous (n = 1) and severe heterozygous familial hypercholesterolaemia. For each treatment, 1.6 fold of the calculated blood volume was processed. Treatments were scheduled at weekly or two-weekly intervals. RESULTS: The smallest DALI-500 configuration was unable to achieve sufficient removal of LDL cholesterol, with the adsorber being exhausted already at desorption of 65% of the calculated blood volume. In contrast, both larger adsorber systems effectively removed lipoproteins until the end of treatment. Therefore, the DALI-750 device was used for long-term treatment. LDL cholesterol (mean pretreatment value: 179 +/- 44 mg/dl) was reduced by 73.4 +/- 7.7% and Lp(a) levels (mean pretreatment value: 43 +/- 33 mg/dl) by 69.5 +/- 8.3%. HDL cholesterol (mean pretreatment value: 47 +/- 15 mg/dl) was reduced by 16.3 +/- 8.0% during the treatment. In the long term, LDL cholesterol was reduced by 54.0 +/- 10.5%--from 259 +/- 101 mg/dl to 119 +/- 19 mg/dl. No serious side effects occurred during the treatment. Long-term evaluation of other laboratory parameters showed a reduction in haemoglobin due to treatment-associated blood loss despite frequent iron supplementation. CONCLUSION: Sufficient reductions in LDL cholesterol and Lp(a) were achieved using the DALI-750 system and the treatment was well tolerated. The easy use and short period of 153 +/- 22 minutes required for each treatment are the major advantages of the DALI system as compared to other available LDL-apheresis devices. Potential particle release from the adsorber into the circulation must be ruled out before the system can be introduced in clinical routine.     

Effect of a chicken-based diet on renal function and lipid profile in patients with type 2 diabetes: a randomized crossover trial

OBJECTIVE: To assess the effect of replacing red meat with chicken in the usual diet and the effect of a low-protein diet on glomerular filtration rate (GFR), urinary albumin excretion rate (UAER), and lipid levels in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A randomized, crossover, controlled trial was conducted with 28 patients with type 2 diabetes (seven women; mean age 58.1 years): 15 patients were normoalbuminuric (UAER <20 microg/min), and 13 patients were microalbuminuric (UAER 20-200 microg/min). A chicken-based diet (red meat replaced with chicken) and a low-protein diet were compared with the patients' usual diet. Patients followed each diet for 4 weeks with a 4-week washout period between. GFR ((51)Cr-EDTA single-injection technique), 24-h UAER (immunoturbidimetry), apolipoprotein B, total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides were measured after each diet. RESULTS: Normoalbuminuric and microalbuminuric patients with diabetes were analyzed separately. In normoalbuminuric patients, GFR after the chicken (101.3 +/- 22.9 ml x min(-1) x 1.73 m(-2)) and low-protein diets (93.8 +/- 20.5 ml x min(-1) x m(-2)) was lower than after the usual diet (113.4 +/- 31.4 ml x min(-1) x 1.73 m(-2); P < 0.05). In microalbuminuric patients, apolipoprotein B levels were lower after the chicken (113.5 +/- 36.0 mg/dl) and low-protein diets (103.5 +/- 40.1 mg/dl) than after the usual diet (134.3 +/- 30.7 mg/dl; P < 0.05). Only the chicken diet reduced UAER (median 34.3 microg/min) compared with the low-protein (median 52.3 microg/min) and usual (median 63.8 microg/min) diets (P < 0.05). Glycemic control and blood pressure did not change after the diets. CONCLUSIONS: A normoproteic diet with chicken as the only source of meat may represent an alternative strategy for treatment of patients with type 2 diabetes and microalbuminuria.     

Oat-derived beta-glucan significantly improves HDLC and diminishes LDLC and non-HDL cholesterol in overweight individuals with mild hypercholesterolemia

OBJECTIVE: To investigate the effect of bread formulated with 6 g of beta-glucan (oat soluble fiber) on serum lipids in overweight normotensive subjects with mild to moderate hypercholesterolemia. DESIGN: Thirty-eight male subjects [mean age 59.8 +/- 0.6 yr, mean body mass index (BMI) 28.3 +/- 0.6 kg/m(2)] who were eligible for the study ate an isocaloric diet for a 1-week period. They were then divided into 2 groups: group A (n = 19), who were maintained on American Heart Association (AHA) Step II diet, including whole wheat bread, and group B (n = 19), who were maintained on AHA Step II diet containing high levels of monounsaturated fatty acids plus bread containing 6 g of beta-glucan (Nutrim-OB) for 8 weeks. Plasma lipids and glucose were measured at baseline and after weeks 8 in all subjects. All subjects were advised to walk for 60 minutes every day. RESULTS: There was a significant increase (upward arrow 27.8%) in plasma high density lipoprotein (HDL) cholesterol in the beta-glucan group (group A) from 39.4 +/- 2.0 to 49.5 +/- 2.1 mg/dL (P < 0.001), but there was no change in group B. There was a significant reduction in total cholesterol in the 2 groups to approximately the same extent: group A, from 232.8 +/- 2.7 mg/dL to 202.7 +/- 6.7 mg/dL; P < 0.001; and group B, from 231.8 +/- 4.3 mg/dL to 194.2 +/- 4.3 mg dL; P < 0.001. Plasma low density lipoprotein (LDL) cholesterol also decreased significantly in the two groups: group A, from 160.3 +/- 2.8 mg/dL to 133.2 +/- 5.4 mg/dL; P < 0.001; group B, from 167.9 +/- 4.3 mg/dL to 120.9 +/- 4.3 mg/dL; P < 0.001; however, the beta-glucan fortified diet was significantly more effective (downward arrow 27.3% vs. downward arrow 16.8%; P < 0.04). There was a small and insignificant reduction in plasma very LDL (VLDL) cholesterol and triglycerides in the two groups. Similarly, non-HDL cholesterol levels were also decreased, with beta-glucan diet producing significantly higher effect (downward arrow 24.5% vs. downward arrow 16.1%; P < 0.04). The beta-glucan diet also produced higher reduction in total cholesterol/HDL cholesterol ratio (downward arrow 33.3% vs. downward arrow 8.4%; P < 0.003) and LDL cholesterol/HDL cholesterol ratio (downward arrow 42.1% vs. downward arrow 13.3%; P < 0.001) than the diet without beta-glucan. The beta-glucan diet also decreased fasting plasma glucose (P < 0.4), whereas the other diet had no effect. Interestingly, both diets reduced body weight and BMI significantly, with beta-glucan diet having a greater effect. CONCLUSIONS: Six grams of beta-glucan from oats added to the AHA Step II diet and moderate physical activity improved lipid profile and caused a decrease in weight and, thus, reduced the risk of cardiovascular events in overweight male individuals with mild to moderate hypercholesterolemia. The diet with added beta-glucan was well accepted and tolerated.     

Metabolic effects of dietary fructose in diabetic subjects.

OBJECTIVE--To assess the metabolic effects of chronic dietary fructose consumption in diabetic subjects. RESEARCH DESIGN AND METHODS--Six type I and 12 type II diabetic subjects consumed, in random order, two isocaloric study diets for 28 days. In one diet, 20% of energy was derived from fructose. In the other diet, < 3% of energy came from fructose, and carbohydrate energy was derived primarily from starch. Both study diets were composed of common foods. All meals were prepared in a metabolic kitchen where all foods were weighed during meal preparation. RESULTS--Mean plasma glucose, urine glucose, and serum glycosylated albumin values were lower during the fructose diet than during the starch diet, but the differences achieved only marginal statistical significance. The day-28 value for mean plasma glucose was 12.5% lower (P = 0.03) during the fructose diet than during the starch diet. At days 14, 21, and 28, fasting serum cholesterol and LDL cholesterol were both significantly higher during the fructose diet than during the starch diet. The day-28 values for serum cholesterol and LDL cholesterol during the fructose diet were 6.9% (P = 0.008) and 10.9% (P = 0.002) higher, respectively, than the corresponding values during the starch diet. No differences were observed between the study diets in fasting serum HDL cholesterol, fasting serum triglycerides, peak postprandial serum triglycerides, or fasting serum lactate. Peak postprandial serum lactate was significantly higher during the fructose diet. Type I and type II diabetic subjects responded to the diets in a consistent way, but type I subjects experienced significantly more hypoglycemia during the fructose diet than during the starch diet. CONCLUSIONS--A high-fructose diet may result in reduced glycemia in diabetic subjects but at the expense of increased fasting serum total and LDL cholesterol.     

Transgenic mice expressing high levels of human apolipoprotein B develop severe atherosclerotic lesions in response to a high-fat diet.

We previously generated transgenic mice expressing human apolipoprotein (apo-) B and demonstrated that the plasma of chow-fed transgenic animals contained markedly increased amounts of LDL (Linton, M. F., R. V. Farese, Jr., G. Chiesa, D. S. Grass, P. Chin, R. E. Hammer, H. H. Hobbs, and S. G. Young 1992. J. Clin. Invest. 92:3029-3037). In this study, we fed groups of transgenic and nontransgenic mice either a chow diet or a diet high in fat (16%) and cholesterol (1.25%). Lipid and lipoprotein levels were assessed, and after 18 wk of diet, the extent of aortic atherosclerotic lesions in each group of animals was quantified. Compared with the female transgenic mice on the chow diet, female transgenic mice on the high-fat diet had higher plasma levels of cholesterol (312 +/- 17 vs 144 +/- 7 mg/dl; P < 0.0001) and human apo-B (120 +/- 8 vs 84 +/- 3 mg/dl; P < 0.0001). The higher human apo-B levels were due to increased plasma levels of human apo-B48; the human apo-B100 levels did not differ in animals on the two diets. In mice on the high-fat diet, most of the human apo-B48 and apo-B100 was found in LDL-sized particles. Compared with nontransgenic mice on the high-fat diet, the transgenic animals on the high-fat diet had significantly increased levels of total cholesterol (312 +/- 17 vs 230 +/- 19 mg/dl; P < 0.0001) and non-HDL cholesterol (283 +/- 17 vs 193 +/- 19 mg/dl; P < 0.0001). The extent of atherosclerotic lesion development within the ascending aorta was quantified by measuring total lesion area in 60 progressive sections, using computer-assisted image analysis. Neither the chow-fed transgenic mice nor the chow-fed nontransgenic mice had significant atherosclerotic lesions. Nontransgenic animals on the high-fat diet had relatively small atherosclerotic lesions (< 15,000 microns 2/section), almost all of which were confined to the proximal 400 microns of the aorta near the aortic valve. In contrast, transgenic animals on the high-fat diet had extensive atherosclerotic lesions (> 160,000 microns 2/section) that were widely distributed throughout the proximal 1,200 microns of the aorta. Thus, human apo-B expression, in the setting of a diet rich in fats, causes severe atherosclerosis in mice.     

Effects of two lipid-lowering,carotenoid-controlled diets on the oxidative modification of low-density lipoproteins in free-living humans

This study compares the effects of two lipid-lowering diets [a diet enriched in MUFAs (monounsaturated fatty acids) and a HCLF (high-carbohydrate/low-fat) diet] with a controlled carotenoid content on risk factors for coronary heart disease, including in vitro copper-induced LDL (low-density lipoprotein) oxidation and serum lipid levels. A randomized crossover dietary intervention study, with two diets each consumed for 14-16 days, was conducted in 18 women and 13 men aged 20-70 years, recruited via personal contacts and advertisements in newspapers. Both diets (MUFA-enriched diet and HCLF diet) contained the same basic foods and had a controlled carotenoid content, high in lycopene. The in vitro copper-induced oxidation of isolated LDL showed a longer lag phase (mean difference 7.4 min in women and 7.34 min in men) after the MUFA-enriched diet compared with the HCLF diet. Serum total cholesterol, LDL cholesterol and carotenoid levels were similar after the two diets. Serum triacylglycerol levels were significantly lower and those of HDL (high-density lipoprotein) cholesterol were significantly higher at the end of the MUFA-enriched diet compared with the HCLF diet. It is concluded that the significantly longer lag phase for oxidation of LDL, the higher HDL cholesterol level and the lower triacylglycerol level in subjects following a carotenoid-controlled, MUFA-enriched diet may decrease the risk of coronary heart disease.     

Familial apolipoprotein AI and apolipoprotein CIII deficiency. Subclass distribution,composition, and morphology of lipoproteins in a disorder associated with premature atherosclerosis.

Lipoprotein classes isolated from the plasma of two patients with apolipoprotein AI (apo AI) and apolipoprotein CIII (apo CIII) deficiency were characterized and compared with those of healthy, age- and sex-matched controls. The plasma triglyceride values for patients 1 and 2 were 31 and 51 mg/dl, respectively, and their cholesterol values were 130 and 122 mg/dl, respectively; the patients, however, had no measurable high density lipoprotein (HDL)-cholesterol. Analytic ultracentrifugation showed that patients'' S degrees f 0-20 lipoproteins possess a single peak with S degrees f rates of 7.4 and 7.6 for patients 1 and 2, respectively, which is similar to that of the controls. The concentration of low density lipoprotein (LDL) (S degrees f 0-12) particles, although within normal range (331 and 343 mg/dl for patients 1 and 2, respectively), was 35% greater than that of controls. Intermediate density lipoproteins (IDL) and very low density lipoproteins (VLDL) (S degrees f 20-400) were extremely low in the patients. HDL in the patients had a calculated mass of 15.4 and 11.8 mg/dl for patients 1 and 2, respectively. No HDL could be detected by analytic ultracentrifugation, but polyacrylamide gradient gel electrophoresis (gge) revealed that patients possessed two major HDL subclasses: (HDL2b)gge at 11.0 nm and (HDL3b)gge at 7.8 nm. The major peak in the controls, (HDL3a)gge, was lacking in the patients. Gradient gel analysis of LDL indicated that patients'' LDL possessed two peaks: a major one at 27 nm and a minor one at 26 nm. The electron microscopic structure of patients'' lipoprotein fractions was indistinguishable from controls. Patients'' HDL were spherical and contained a cholesteryl ester core, which suggests that lecithin/cholesterol acyltransferase was functional in the absence of apo AI. The effects of postprandial lipemia (100-g fat meal) were studied in patient 1. The major changes were the appearance of a 33-nm particle in the LDL density region of 1.036-1.041 g/ml and the presence of discoidal particles (12% of total particles) in the HDL region. The latter suggests that transformation of discs to spheres may be delayed in the patient. The simultaneous deficiency of apo AI and apo CIII suggests a dual defect in lipoprotein metabolism: one in triglyceride-rich lipoproteins and the other in HDL. The absence of apo CIII may result in accelerated catabolism of triglyceride-rich particles and an increased rate of LDL formation. Additionally, absence of apo CIII would favor rapid uptake of apo E-containing remnants by liver and peripheral cells. Excess cellular cholesterol would not be removed by the reverse cholesterol transport mechanism since HDL levels are exceedingly low and thus premature atherosclerosis occurs.