Relationship of regional adiposity to insulin resistance and serum triglyceride levels in nonobese Japanese type 2 diabetic patients

The aim of this study was to investigate the relationships between insulin resistance and regional abdominal fat area, body mass index (BMI), and serum lipid profile in nonobese Japanese type 2 diabetic patients. A total of 63 nonobese Japanese type 2 diabetic patients aged 45 to 83 years were examined. The duration of diabetes was 8.4 +/- 0.8 years. BMI, glycosylated hemoglobin (HbA(1c)) levels, and fasting concentrations of plasma glucose, serum lipids (total cholesterol, high-density lipoprotein [HDL] cholesterol, and triglycerides), and serum insulin were measured. The low-density lipoprotein (LDL) cholesterol level was calculated using the Friedewald formula (LDL cholesterol = total cholesterol - HDL cholesterol - 1/5 triglycerides). Insulin resistance was estimated by the homeostasis model assessment (HOMA-IR). Computed tomography (CT) was used to measure cross-sectional abdominal subcutaneous and visceral fat areas in all the patients. Adipose tissue areas were determined at the umbilical level. Subcutaneous and visceral abdominal fat areas were 136.5 +/- 6.0 and 86.0 +/- 4.1 cm(2), respectively. Univariate regression analysis showed that insulin resistance was positively correlated with subcutaneous (r =.544, P <.001) and visceral (r =.408, P =.001) fat areas, BMI (r =.324, P =.009), HbA(1c) (r =.254, P =.001), serum triglycerides (r =.419, P <.001), and serum LDL cholesterol (r =.290, P =.019) levels and was negatively correlated with serum HDL cholesterol level (r =.254, P =.041). Multiple regression analyses showed that insulin resistance was independently predicted by the areas of subcutaneous (F = 6.76, P <.001) and visceral (F = 4.61, P <.001) abdominal fat and serum triglycerides (F = 8.88, P <.001) level, which explained 36.9% of the variability of insulin resistance. Moreover, the present study demonstrated that whereas BMI was positively correlated with visceral (r =.510, P <.001) and subcutaneous (r =.553, P <.001) fat areas, serum triglyceride level was positively associated with visceral (r =.302, P =.015), but not with subcutaneous (r =.222, P =.074) fat area. From these results, it can be suggested that (1) both subcutaneous and visceral abdominal fat areas are independently associated with insulin resistance and (2) visceral fat area, but not the subcutaneous one, is associated with serum triglyceride levels in our nonobese Japanese type 2 diabetic patients.     

Interrelationships of spontaneous growth hormone axis activity, body fat, and serum lipids in healthy elderly women and men

Aging is associated with decreased growth hormone (GH) secretion and plasma insulin-like growth factor-I (IGF-I) levels, increased total and abdominal fat, total and low-density lipoprotein (LDL) cholesterol, and triglycerides, and reduced high-density lipoprotein (HDL) cholesterol. Similar changes in lipids and body composition occur in nonelderly GH-deficient adults and are reversed with GH administration. To examine whether GH/IGF-I axis function in the elderly is related to the lipid profile independently of body fat, we evaluated GH secretion, serum IGF-I and IGF binding protein-3 (IGFBP-3) levels, adiposity via the body mass index (BMI), waist to hip ratio (WHR), dual-energy x-ray absorptiometry (DEXA), and magnetic resonance imaging (MRI), and circulating lipids in 101 healthy subjects older than 65 years. Integrated nocturnal GH secretion (log IAUPGH) was inversely related (P < .005) to DEXA total and abdominal fat and MRI visceral fat in both genders. Log IAUPGH was inversely related to visceral fat in women (P < .005) and men (P < .0001), but was not significantly related to total fat in either gender. In women, log IAUPGH was related inversely to total and LDL cholesterol and positively to HDL cholesterol (P < .008). In men, log IAUPGH was inversely related to total cholesterol and triglycerides (P < .005). In women, HDL cholesterol was inversely related to the WHR (P < .005). In men, triglycerides were positively related (P < .001) to the WHR and DEXA abdominal and MRI visceral fat. Multivariate regression revealed log IAUPGH, but not DEXA total body fat, to be an independent determinant of total (P < .001 for women and P = .01 for men) and LDL (P < .007 and P = .05) cholesterol in both sexes and of HDL cholesterol (P < .005) and triglycerides (P < .03) in women. Log IAUPGH, but not DEXA abdominal fat, was related to total (P < .005 and P < .03) and LDL (P < .03 and P = .05) cholesterol in both genders and to HDL in women (P < .05). Log IAUPGH, but not MRI visceral fat, was related to total cholesterol (P < .03 and P = .05) in women and men. Age, IGF-I, and IGFBP-3 were not significantly related to any body fat or lipid measures, except for a positive correlation of IGF-I with triglycerides in men. Thus, endogenous nocturnal GH secretion predicts total, LDL, and HDL cholesterol levels independently of total or abdominal fat, suggesting that it is an independent cardiometabolic risk factor in healthy elderly people.     

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.     

Consumption of an oil composed of medium chain triacyglycerols,phytosterols, and N-3 fatty acids improves cardiovascular risk profile in overweight women

Medium chain triacylglycerols (MCT) have been suggested as efficacious in weight management because they possess greater thermogenic qualities relative to long chain triacylglycerols; however, MCT may also increase circulating lipid concentrations, possibly increasing risk of cardiovascular disease (CVD). The present objective was to examine the effect of a diet supplemented with a functional oil (FctO) composed of energy expenditure-enhancing MCT (50% of fat), cholesterol-lowering phytosterols (22 mg/kg body weight), and triacylglycerol-suppressing n-3 fatty acids (5% of fat), versus a beef tallow-based diet (BT), on plasma lipid and aminothiol concentrations. In a randomized, single-blind, crossover design, partially-inpatient trial, 17 overweight women consumed each oil as part of a controlled, supervised, targeted energy balance diet for 27 days, with 4 or 8 weeks of washout between phases. Mean plasma total cholesterol concentration was lower (P <.0001), by 9.1%, on FctO (4.37 +/- 0.20 mmol/L) versus BT (4.80 +/- 0.20 mmol/L). Mean plasma low-density lipoprotein (LDL) cholesterol was also lower (P <.0001) following FctO (2.39 +/- 0.15 mmol/L) versus BT (2.86 +/- 0.16 mmol/L), representing a 16.0% difference between diets. High-density lipoprotein (HDL) cholesterol and circulating triacylglycerol concentrations remained unaffected by treatment. Ratios of HDL:LDL and HDL:total cholesterol were higher (P <.01) by 22.0% and 11.0%, respectively, on FctO versus BT. Plasma total homocysteine remained unchanged with FctO, but decreased (P <.05) with control, hence higher (P <.05) end points were observed with FctO (6.95 +/- 0.33 micromol/L) versus BT (6.27 +/- 0.28 micromol/L). Plasma glutathione increased (P <.05) by 0.44 micromol/L with FctO supplementation. In conclusion, despite equivocal effects on homocysteine levels, consumption of a functional oil composed of MCT, phytosterols, and n-3 fatty acids for 27 days improves the overall cardiovascular risk profile of overweight women.     

Endurance exercise training raises high-density lipoprotein cholesterol and lowers small low-density lipoprotein and very low-density lipoprotein independent of body fat phenotypes in older men and women

Endurance exercise training improves plasma lipoprotein and lipid profiles and reduces cardiovascular disease risk. However, the effect of endurance exercise training, independent of diet and body fat phenotypes, on plasma lipoprotein subfraction particle concentration, size, and composition as measured by nuclear magnetic resonance (NMR) spectroscopy is not known. We hypothesized that 24 weeks of endurance exercise training would independently improve plasma lipoprotein and lipid profiles as assessed by both conventional and novel NMR measurement techniques. One hundred sedentary, healthy 50- to 75-year-olds following a standardized diet were studied before and after 24 weeks of aerobic exercise training. Lipoprotein and lipid analyses, using both conventional and NMR measures, were performed at baseline and after 24 weeks of exercise training. Relative and absolute maximum oxygen consumption increased 15% with exercise training. Most lipoprotein and lipid measures improved with 24 weeks of endurance exercise training, and these changes were consistently independent of baseline body fat and body fat changes with training. For example, with exercise training, total cholesterol, triglycerides, and low-density lipoprotein cholesterol (LDL-C) decreased significantly (2.1+/-1.8 mg/dL, P=.001; -17+/-3.5 mg/dL, P<.0001; and -0.7+/-1.7 mg/dL, P<.0001, respectively), and high-density lipoprotein cholesterol subfractions (HDL3-C and HDL2-C) increased significantly (1.9+/-0.5 mg/dL, P=.01, and 1.2+/-0.3 mg/dL, P=.02, respectively). Particle concentrations decreased significantly for large and small very low-density lipoprotein particles (-0.7+/-0.4 nmol/L, P<.0001, and -1.1+/-1.7 nmol/L, P<.0001, respectively), total, medium, and very small LDL particles (-100+/-26 nmol/L, P=.01; -26+/-7.0 nmol/L, P=.004; and -103+/-27 nmol/L, P=.02, respectively), and small HDL particles (-0.03+/-0.4 micromol/L, P=.007). Mean very low-density lipoprotein particle size also decreased significantly (-1.7+/-0.9 nm, P<.0001) and mean HDL particle size increased significantly with exercise training (0.1+/-0.0 nm, P=.04). These results show that 24 weeks of endurance exercise training induced favorable changes in plasma lipoprotein and lipid profiles independent of diet and baseline or change in body fat.     

Combined effect of vegetable protein (soy) and soluble fiber added to a standard cholesterol-lowering diet.

Dietary treatment of hyperlipidemia focuses on reducing saturated fat and dietary cholesterol. Other aspects of diet are not emphasized at present, despite growing evidence that a number of plant components decrease serum cholesterol. We therefore determined whether a combination of two plant components, vegetable protein and soluble fiber, further reduce serum lipids when incorporated into the currently advocated low-saturated-fat diet. Thirty-one hyperlipidemic men and women ate two 1-month low-fat (<7% of total energy from saturated fat), low-cholesterol (<80 mg cholesterol/d) metabolic diets in a randomized crossover study. The major differences between test and control diets were an increased amount of vegetable protein (93% v 23% of total protein), of which 33 g/d was soy, and a doubling of soluble fiber. Fasting blood samples were obtained at the start and end of each phase. On the last 3 days of each phase, fecal collections were obtained. Compared with the low-fat control diet, the test diet decreased total cholesterol (6.2% +/- 1.2%, P < .001), low-density lipoprotein (LDL) cholesterol (6.7% +/- 1.7%, P < .001), apolipoprotein B (8.2% +/- 1.2%, P < .001), and the ratios of LDL to high-density lipoprotein (HDL) cholesterol (6.3% +/- 2.0%, P = .004) and apolipoprotein B to A-I (5.4% +/- 1.5%, P = .001). A combination of vegetable protein and soluble fiber significantly improved the lipid-lowering effect of a low-saturated-fat diet. The results support expanding the current dietary advice to include increased vegetable protein and soluble fiber intake so that the gap in effectiveness between a good diet and drug therapy is reduced.     

C-reactive protein and insulin resistance in non-obese Japanese type 2 diabetic patients

The aim of the present study was to investigate the relationship between C-reactive protein (CRP) and insulin resistance in non-obese Japanese type 2 diabetic patients. A total of 135 non-obese Japanese type 2 diabetic patients (96 men and 39 women, aged 36 to 83 years, with a body mass index [BMI] of 16.2 to 26.8 kg/m2) were studied. BMI, glycosylated hemoglobin (HbA(1c)), fasting concentrations of plasma glucose, serum lipids (triglycerides, low-density lipoprotein [LDL] cholesterol, high-density lipoprotein [HDL] cholesterol, and total cholesterol), CRP, and fibrinogen were measured. LDL cholesterol was calculated using the Friedewald formula. Insulin resistance was estimated by the insulin resistance index of homeostasis model assessment (HOMA-IR). Univariate regression analysis showed that CRP value was positively correlated to age (r = 0.218, P =.012), BMI (r = 0.239, P =.006), HOMA-IR (r = 0.397, P <.0001), triglycerides (r= 0.310, P <.005), LDL cholesterol (r= 0.179, P =.038), and fibrinogen (r = 0.371, P <.0001) levels and inversely correlated to HDL cholesterol (r = 0.174, P =.044) level in our diabetic patients. Multiple regression analysis showed that CRP was independently predicted by HOMA-IR (P<.0001, F = 11.6) and fibrinogen (P<.0001, F = 34.2), which explained 23.5% of the variability of CRP in our non-obese Japanese type 2 diabetic patients. These results indicate that insulin resistance and fibrinogen level are independent predictors of CRP in non-obese Japanese type 2 diabetic patients.     

Platelet count is independently associated with insulin resistance in non-obese Japanese type 2 diabetic patients

The aim of the present study was to investigate the relationship between platelet count and insulin resistance in non-obese Japanese type 2 diabetic patients. A total of 163 non-obese Japanese type 2 diabetic patients (112 men and 51 women, aged 36 to 84 years, body mass index [BMI] 16.2 to 26.9 kg/m(2)) were studied. In conjunction with BMI, glycosylated hemoglobin (HbA(1c)), fasting concentrations of plasma glucose and serum lipids (triglycerides, low-density lipoprotein [LDL] cholesterol, high-density lipoprotein [HDL] cholesterol, and total cholesterol), and hematological parameters (platelets, white blood cell count, red blood cell count, hematocrit, hemoglobin) were measured. LDL cholesterol was calculated using the Friedewald formula. Insulin resistance was estimated by the insulin resistance index of homeostasis model assessment (HOMA-IR). Univariate regression analysis showed that HOMA-IR was positively correlated to BMI (r = 0.465, P <.0001), HbA(1c) (r = 0.423, P <.0001), platelet count (r = 0.310, P <.0001), triglycerides (r = 0.277, P <.0005), white blood cell count (r =.222, P =.005), red blood cell count (r = 0.210, P =.008), hematocrit (r = 0.156, P =.047), total cholesterol (r = 0.178, P =.023), and systolic (r = 0.216, P =.011) and diastolic (r = 0.263, P =.002) blood pressure, and inversely correlated to HDL cholesterol (r = -0.312, P <.0001) level in our diabetic patients. Multiple regression analysis showed that HOMA-IR was independently predicted by BMI (P <.0001, F = 22.45), HbA(1c) (P <.0001, F = 16.15), platelet count (P <.0001, F = 10.75), and serum triglycerides (P <.0001, F = 10.47) levels, which explained 34% of the variability of HOMA-IR in non-obese Japanese type 2 diabetic patients. These results indicate that not only BMI, HbA(1c), and triglycerides levels but also platelet counts are independent predictor of insulin resistance in non-obese Japanese type 2 diabetic patients.     

Intake of trans fatty acids and low-density lipoprotein size in a Costa Rican population

Intervention studies show that dietary composition altered low-density lipoprotein (LDL) particle size, but population studies are scarce, and the potential effects of trans fatty acids (FA) on LDL size are unknown. Trans FA intake has been associated with a more atherogenic lipid profile and increased coronary heart disease (CHD). We examined the association between dietary intake, including trans FA and LDL size, in 414 randomly selected subjects living in Puriscal, Costa Rica. Dietary intake was assessed by a validated food frequency questionnaire (FFQ). Women had larger LDL size (A) compared with men (263 v 261), and large LDL particles were correlated with increased intake (% energy) of protein (P =.005), animal fat (P =.041), trans FA (P <.0001), and decreased intake of carbohydrate (P =.052) in sex-, age-, and total energy intake-adjusted models. The correlation between trans FA intake and large LDL was significant in multivariate models that included dietary and nondietary factors; a 1% difference in trans FA was associated with a 2.44 A increase in LDL size (P =.004). In sum, it is possible that the effects of dietary factors, such as intake of trans FA on CHD are mediated through their effects on LDL size.     

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.     

Naturally-occurring phytosterols in the usual diet influence cholesterol metabolism in healthy subjects

Background and aimsModulation of cholesterol absorption is potentially an effective way of lowering blood cholesterol levels and decreasing inherent cardiovascular risk in the general population. It is well established that cholesterol absorption efficiency can be modified by the intake of foods enriched with gram-doses of phytosterols, but little is known about the effects of phytosterols in the usual diet, even though moderate doses have been reported to affect whole-body cholesterol metabolism. A way to indirectly measure cholesterol synthesis and absorption rates is by quantification of serum non-cholesterol sterols. The aim of this study was to investigate the role of naturally occurring phytosterol intake on cholesterol absorption and serum cholesterol concentrations in a Spanish free-living population.Methods and resultsA total of 85 healthy volunteers were studied regarding their dietary habits (using a validated food frequency questionnaire), lipid profile and surrogate markers of cholesterol metabolism. Subjects were classified into tertiles of total phytosterol intake, and differences in lipid profile and markers of cholesterol metabolism were assessed by multivariate linear regression models adjusted for various confounders. The estimated daily intake of phytosterols and cholesterol was 489 (median) and 513 (mean) mg, respectively. Both serum low-density lipoprotein (LDL)-cholesterol concentration and sitosterol-to-cholesterol ratio adjusted by sitosterol intake (a surrogate marker of intestinal cholesterol absorption) decreased significantly (p < 0.05, both) across tertiles of phytosterol intake.ConclusionModerate doses of phytosterols in the habitual diet might have a protective effect on the lipid profile via decreasing cholesterol absorption.     

Associations between the fatty acid content of triglyceride, visceral adipose tissue accumulation, and components of the insulin resistance syndrome

Many factors are involved in the development of the insulin resistance syndrome, such as visceral obesity and the type of dietary fat. The main purpose of this study was to investigate the relationships between fatty acid content of triglyceride (TG), visceral adipose tissue (AT) accumulation, and metabolic components of the insulin resistance syndrome in a group of 97 Caucasian men with a mean age of 45.1 +/- 7.2 years (29 to 63 years). To reach these objectives, Spearman correlations, group comparisons, and stepwise multiple regression analyses were performed. The proportion of palmitic acid (16:0) in the TG fraction was positively associated with plasma fasting insulin (r =.25, P =.03), diastolic (r =.45, P <.001), and systolic (r =.29, P =.003) blood pressure. On the other hand, the proportion of alpha-linolenic acid (18:3n-3) was associated negatively with apolipoprotein (apo) B (r = -.29, P =.005) and positively with low-density lipoprotein (LDL) diameter (r =.29, P =.007), while the proportion of gamma-linolenic acid (18:3n-6) was associated negatively with plasma TG (r = -.33, P =.003), diastolic (r = -.29, P =.01), and systolic (r = -.35, P =.002) blood pressure and plasma fasting insulin (r = -.37, P =.0005) and positively with high-density lipoprotein (HDL)(2)-cholesterol (r =.27, P =.01) and LDL diameter (r =.25, P =.02). Stepwise multiple regression analyses were conducted to determine the contribution of visceral AT, body fat mass, and the fatty acid content of TG to the variance of metabolic variables studied. It was found that visceral AT contributed significantly to the variance in plasma TG (R(2) = 20.7%, P <.0001), apo B (R(2) = 9.0%, P =.007), HDL(2)-cholesterol (R(2) = 17.9%, P <.0001), LDL diameter (R(2) = 4.9%, P =.02), and area under the glucose curve (AUC-glucose) (R(2) = 8.2%, P =.006). On the other hand, body fat mass contributed significantly to the variance in fasting insulin (R(2) = 19.7%, P <.0001) and diastolic (R(2) = 6.8%, P =.007) and systolic (R(2) = 10.5%, P =.01) blood pressure. At least one fatty acid made a significant contribution to the variance of each metabolic variable studied. In fact, the proportion of 18:3n-6 contributed significantly to the variance in both TG (R(2) = 8.9%, P = 0.007) and HDL(2)-cholesterol (R(2) = 6.0%, P =.01). Moreover, 18:3n-3 contributed to the variance of apo B (R(2) = 7.0%, P =.02), while 18:3n-6 made the largest contribution to the variance of LDL diameter (R(2) = 7.6%, P =.02). Finally, 16:0 significantly contributed to the variance of AUC-glucose (R(2) = 11.4%, P =.0003), diastolic (R(2) = 25.2%, P <.0001), and systolic (R(2) = 6.8%, P =.002) blood pressure. In summary, results of this study suggest that the fatty acid content of TG is associated with many metabolic variables of the insulin resistance syndrome independently of body fat mass or visceral AT accumulation.     

Apolipoprotein E polymorphism modulates the association between obesity and dyslipidemias during young adulthood: The Bogalusa Heart Study

To elucidate to what extent apolipoprotein (apo) E polymorphism modulates obesity-induced dyslipidemias during young adulthood, longitudinal data on 759 individuals (72% white/28% black; initial and follow-up mean age, 25.9 and 32.7 years) were examined. Among both races and the total sample, the apo E2 group (with E2/2 or E2/3 phenotype) had significantly lower and the apo E4 (with E4/4 or E3/4 phenotype) group higher low-density lipoprotein (LDL) cholesterol than the apo E3 (with E3/3 phenotype) group at both examinations. In addition, the apo E2 group displayed higher high-density lipoprotein (HDL) cholesterol in the total sample. No allele-specific effect was noted for the longitudinal changes (Delta). An increase in Delta adiposity, measured as Delta body mass index (BMI), was accompanied by higher increase in Delta LDL cholesterol in the e4 carriers than the e2 carriers among the whites (P <.05) and the total sample (P <.01); an increase in Delta triglycerides and decrease in Delta HDL cholesterol in the e2 carriers than the e4 carriers among all the groups (P <.05 to.001). Among the apo E phenotype groups, the incidence of high (>75th percentile specific for race and sex) LDL cholesterol at follow-up was in the order E4 > E3 > E2 both in the obese (BMI > 30; P for trend =.033) and the nonobese (BMI < 25; P for trend =.035) groups. Although the increase of low (<25th percentile specific for race and sex) HDL cholesterol or high triglycerides showed no apo E phenotype-specific trend, the incidence of high triglycerides without high LDL cholesterol was in the order E2 > E3 > E4 only in the obese group (P for trend =.025). The prevalence trend for dyslipidemias at follow-up among the persistently obese and nonobese groups also gave similar results. Thus, apo E gene locus influences not only the levels of certain lipoprotein variables during young adulthood, but also modulates the association between obesity and dyslipidemias.     

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.     

Impact of cardiac rehabilitation on coronary risk factors, inflammation, and the metabolic syndrome in obese coronary patients

Obesity is a coronary heart disease (CHD) risk factor and is prevalent in patients with CHD. The authors reviewed data in 235 consecutive patients before and after formal cardiac rehabilitation and exercise training (CRET) programs and analyzed data in 72 lean patients (body mass index [BMI] <25 kg/m(2)) vs 73 obese patients (BMI>or=30 kg/m(2)). At baseline, obese patients were significantly younger (P<.0001); had higher percentage of body fat (P<.0001) and more dyslipidemia, including higher triglycerides (TG; P<.01), lower high-density lipoprotein (HDL) cholesterol (P<.0001), and higher TG/HDL ratio (P<.0001); and had higher prevalence of metabolic syndrome (61% vs 26%; P<.01) compared with lean patients. Following CRET, obese patients had small, but statistically significant, improvements in obesity indices, including weight (P<.01), BMI (P<.01), and percentage of fat (P=.03), and had more significant improvements in peak exercise capacity (P<.001), HDL cholesterol (P<.001), C-reactive protein (P<.01), behavioral characteristics, and quality of life (P<.0001). The prevalence of metabolic syndrome fell (62% to 51%; P=.1). These results support the benefits of CRET to reduce overall risk in obese patients with CHD.     

Clinical evaluation of plasma high-density lipoprotein subfractions (HDL2, HDL3) in non-insulin-dependent diabetics with coronary artery disease

STATEMENT OF THE PROBLEM: Low levels of high-density lipoprotein cholesterol (HDL-C) have a strong association with coronary artery disease (CAD) in patients with non-insulin-dependent diabetes mellitus (NIDDM). In this study, we tried to evaluate whether one or both of the major HDL subclasses (HDL2, HDL3) is strongly associated with the risk of CAD in NIDDM subjects. METHODS: The separation of HDL subclasses was carried out by ultracentrifugation in a Beckman Airfuge. HDL2 subclass was isolated from the supernatant and its cholesterol content was measured enzymatically. Plasma HDL3 cholesterol was calculated as the difference between results for total HDL cholesterol and HDL2 cholesterol. RESULTS: NIDDM patients with CAD had significantly higher triglyceride levels compared to either control (217.09+/-55.04 versus 89.62+/-31.29 mg/dl, P=.001) or CAD patients without NIDDM (217.09+/-55.04 versus 156.28+/-46.39 mg/dl, P<.05). However, in the diabetic patients with CAD, there was a statistically significant decrease in HDL cholesterol (39.63+/-8.59 versus 55.86+/-13.49 mg/dl, P<.01), HDL2 cholesterol (8.74+/-3.28 versus 16.95+/-5.73 mg/dl, P<.001), and HDL3 cholesterol (31.23+/-7.41 versus 38.91+/-8.93 mg/dl, P<.05) in comparison to nondiabetic controls. Moreover, in the comparison between non-insulin-dependent diabetics with CAD and CAD subjects without NIDDM, HDL cholesterol (39.63+/-8.59 versus 46.13+/-6.33 mg/dl, P<.05) and HDL2 cholesterol (8.74+/-3.28 versus 11.84+/-4.01 mg/dl, P<.02) were significantly reduced, while HDL3 cholesterol levels were (31.23+/-7.41 versus 34.29+/-7.94 mg/dl, P=.92) unaltered. Additionally, the percentage reduction of cholesterol in HDL2 fraction was proportionately greater than the decrease in HDL3 subclass in both comparisons. Moreover, in NIDDM with CAD, HDL cholesterol was reduced by 29% and 14%, HDL2 cholesterol by 48% and 26%, and HDL3 cholesterol by 20% and 9%, compared relatively to controls and CAD subjects without NIDDM. CONCLUSIONS: In conclusion, HDL2 is the more variable subclass and reflects changes in HDL. This suggests that the protective role of total HDL against CAD is mainly mediated through HDL2 fraction. Therefore, HDL2 might be a better predictor of coronary heart disease than total HDL, in non-insulin-dependent diabetes mellitus.     

Release of cholesterol from cell membranes to postprandial plasma from mildly hypercholesterolemic subjects: the effect of meals rich in olive and safflower oils

Triglyceride-rich lipoproteins increase net transport of cell cholesterol to postprandial plasma from healthy subjects after a meal rich in fat and cholesterol. The aim of the present study was to determine the effect of meals rich in polyunsaturated fats (PUFA) and monounsaturated fats (MUFA) and low in cholesterol on net in vitro transport of cholesterol from red blood cells (RBCs) to postprandial plasma from 21 men with mild to moderate hypercholesterolemia in a randomized, crossover trial. Cholesterol concentration increased by 12% due to accumulation of cell cholesterol in fasted hypercholesterolemic plasma incubated with a 2/1 (vol/vol) excess of RBCs at 37 degrees C for 18 hours. The increase in cell cholesterol in plasma was mainly localized in the low-density lipoprotein (LDL) fraction (64%) and the remainder was approximately equally divided between the very-low-density lipoprotein (VLDL) and high-density lipoprotein (HDL) fractions. Accumulation of cell cholesterol in the LDL fraction prevented the significant decrease in LDL cholesterol in plasma incubated alone. When RBCs were incubated with postprandial plasma isolated 4 hours and 6 hours after liquid meals rich in safflower and olive oils, the accumulation of cell cholesterol in plasma increased significantly (11%, P <.004) above values for fasted plasma and irrespective of the type of fat in the meal. Also, the content of cell cholesterol increased significantly (70%, P <.001) in triglyceride (TG)-rich lipoproteins and decreased significantly (P =.006) in the LDL fraction, which remained the main ultimate destination of cell cholesterol in postprandial plasma. The increased loss of cell cholesterol to fasted and postprandial plasma was closely correlated (r > 0.823, P <.001) with the concomitant increase in plasma cholesteryl esters (CE) generated by lecithin cholesterol acyltransferase (LCAT) activity. There was a small (5%), significant (P <.001) increase in plasma cholesterol esterification in postprandial plasma. These data suggest that high-fat meals rich in MUFA and PUFA and low in cholesterol may produce a small postprandial increase in the capacity of plasma to accept cell membrane cholesterol that is limited by a concomitant small increase in plasma cholesterol esterification, in hypercholesterolemic subjects. Thus, low-fat, lipid-lowering diets may have a minimal effect on this capacity but will reduce levels of atherogenic LDL cholesterol that appear to be maintained by diffusion of cell cholesterol to plasma.     

Effects of short- and long-term growth hormone replacement on lipoprotein composition and on very-low-density lipoprotein and low-density lipoprotein apolipoprotein B100 kinetics in growth hormone-deficient hypopituitary subjects

In this study, we concurrently examined the effects of 8 and 40 weeks of growth hormone replacement (GHR) on lipids, lipoprotein composition, low-density lipoprotein (LDL) size, very-low-density lipoprotein (VLDL) apolipoprotein (apo)B kinetics and LDL apoB kinetics. Eight weeks of GHR did not alter lipid profiles. Forty weeks of GHR increased high-density lipoprotein-cholesterol (HDL-C) concentration (P =.01), nonsignificantly reduced LDL-C (P =.06), and reduced the HDL/LDL-C ratio (P =.04). Forty weeks of GHR increased HDL free cholesterol (P =.03), total cholesterol (P =.01), and cholesterol ester (P <.01) concentrations. No other significant changes in VLDL, LDL, or HDL composition or LDL size were noted at any time. Eight weeks of GHR reduced VLDL apoB absolute secretion rate (ASR, P =.03), with nonsignificant reductions in fractional secretion rate (FSR, P =.09) and pool size (P =.09). After 40 weeks of GHR, the VLDL apoB ASR, FSR, and pool size were not significantly different from baseline. Forty weeks of GHR increased both LDL apoB FSR (P =.02) and LDL apoB ASR (P =.04), with a small decrease in pool size. Thus, GHR may have important antiatherogenic effects; HDL-C increased, LDL-C was nonsignificantly reduced, the total/HDL-C ratio was reduced, VLDL apoB production was reduced, and LDL apoB turnover was increased.     

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.     

Reduction of the plasma LDL-cholesterol level among young healthy men as a result of the change from butter to soft margarine in the unbalanced diet

The aim of the study was to evaluate the level of lipid profile on 83 healthy males consuming soft type margarine instead of butter, in their unbalanced diet. For this purpose double blind, cross-over methodology was applied. After stabilization period of consuming the diet, the whole sample was randomly divided into two subgroups (A n--37; B n--46). First group was consuming 15 g of the butter twice a day (30 g in total) and the second identically packed soft type margarine (also twice a day 15 g; 30 g in total) containing high level (33.3 g/100 g) of polyunsaturated fatty acids. After four weeks, the diet of subgroups was mutually exchanged--group consuming margarine consumed butter and the opposite. The feeding pattern of both groups was monitored with the aid of FOOD 2 computer programme. The group under investigation consisted of healthy males at the age 23.3 +/- 2.5, BMI 24.4 +/- 3.9 kg/m2; WHR 0.82 + -0.06 and normal blood pressure. Exchange of butter into soft margarine caused the increase of P/S ratio from 0.30 to 0.78 in their diet. Both investigated groups shoved average decrease of 10.7% of blood cholesterol content (in group A 13.8%), LDL cholesterol of about 9.8% and triglycerides ca 12.7% (higher decrease in group B--16.7%). Both groups while on margarine diet shoved small decrease of HDL cholesterol (3.9%). It can not be the matter of serious concern due to average HDL content in both groups was ca 52 mg/dl (ca 1.4 mmol/l)--it means considerably excessive the limited risk (35 mg/dl; 0.90 mmol/l). Application of the margarine diet in group A caused the decrease the ratios of total cholesterol to HDL cholesterol from 3.84 into 3.52; whereas in group B from 4.15 into 3.75. It was also concluded, that the low trans isomer margarine show no effect on lipoprotein Lp(a). Back to the diet with butter after 4 weeks carry down the beneficial effects of diet with margarine on lipid profile. The results indicate that for lipid profile the consumption of soft margarine was more beneficial than butter, even for unbalanced diet.