Changes In Lipoprotein Subfractions Research Articles

Effects of portable pedal machines at work on lipoprotein subfraction profile in sedentary workers – the REMOVE study

BackgroundSedentary behaviour at work is a major cause of atherosclerosis, particularly in tertiary workers. However, no studies have ever assessed the effect of active workstation on lipoprotein subfraction profile. This study aimed to evaluate the effect of 12-week portable pedal machines (PPMs) on lipoprotein subfraction profile among healthy sedentary workers.MethodsHealthy administrative workers were randomized into an intervention group using PPMs for 12 weeks or a control group using normal-desk. Lipoprotein subfractions were assessed using Lipoprint® electrophoresis. Main outcomes were explored using mixed models with sensitivity analyses (four models).ResultsWe included 40 participants (43.7 ± 8.6 years old, 100% women, BMI 23.8 ± 3.4 kg/m2; sedentary time at work 7.7 ± 1.8 h/day). Groups did not differ at baseline in any outcomes. 32 participants finished the trial. Changes in lipoprotein subfractions were especially marked for LDL profile. There was an interaction time x group for all parameters related to LDL and their subfractions: total LDL-cholesterol (p = 0.012), LDL particle size (p = 0.027), large LDL subfractions 1 and 2 (p = 0.001), and small dense LDL subfractions 3 to 7 (p = 0.046), using the crude model. The interaction reflects difference in the direction of changes between groups. The LDL particle size significantly increased in the intervention group (from 271.9 ± 2.5 at t0 to 272.8 ± 1.9 Ångström at t1, p = 0.037) while it did not change in the control group (272.5 ± 1.7 at t0 to 271.8 ± 1.5Å at t1, p = 0.52). All interactions were constantly significant whatever the models. Influencing variables were mainly stress at work that was associated with an increase in total LDL-cholesterol (coefficient 3.15, 95CI 0.20 to 6.11 mg/dl, p = 0.038), and BMI that was associated with Large-LDL, Large-HDL, IDL-C and triglycerides.ConclusionsLipoprotein profile was improved after a 12-week PPMs intervention at work in healthy administrative workers. Changes were mainly showed for LDL and LDL subfractions. Lipoprotein profile was worsened by stress at work, BMI and age.Trial registrationNCT04153214.

Changes in soluble LDL receptor and lipoprotein fractions in response to diet in the DIETFITS weight loss study

Circulating levels of the soluble ligand-binding ectodomain of the LDL receptor (sLDLR) that is proteolytically cleaved from the cell surface have been shown to correlate with plasma triglycerides, but the lipid and lipoprotein effects of longitudinal changes in sLDLR have not been examined. We sought to assess associations between changes in sLDLR and detailed lipoprotein measurements between baseline and 6 months in participants in the DIETFITS (Diet Intervention Examining The Factors Interacting with Treatment Success) weight loss trial who were randomly assigned to the low-fat (n = 225) or low-carbohydrate (n = 236) diet arms. sLDLR was assayed using a proteomic procedure, lipids and apoprotein (apo) B and apoAI were measured by standard assays, and lipoprotein particle subfractions were quantified by ion mobility methodology. Changes in sLDLR were significantly positively associated with changes in plasma cholesterol, triglycerides, apoB, large-sized and medium-sized VLDL, and small and very small LDL, and inversely with changes in large LDL and HDL. The lipoprotein subfraction associations with sLDLR were independent of age, sex, diet, and BMI, but all except for large LDL were reduced to insignificance when adjusted for triglyceride change. Principal component analysis identified three independent clusters of changes in lipoprotein subfractions that accounted for 78% of their total variance. Change in sLDLR was most strongly correlated with change in the principal component that was loaded positively with large VLDL and small and very small LDL and negatively with large LDL and HDL. In conclusion, sLDLR is a component of a cluster of lipids and lipoproteins that are characteristic of atherogenic dyslipidemia.

Improving Cardiovascular Risk in Postmenopausal Women with an (-)-Epicatechin-Based Nutraceutical: A Randomly Assigned, Double-Blind vs. Placebo, Proof-of-Concept Trial.

Age-adjusted rates of cardiovascular disease (CVD) are higher in men than in women. CVD risk-factor outcomes are underrecognized, underestimated, and undertreated in women because the clinical expressions in women differ from those of men. There are no universally accepted recommendations on what to do in women when the values of fasting glucose, blood pressure, and lipids are only slightly altered or at borderline values. We reported the positive effects on CVD risk markers using cacao by-products, showing that alternative approaches can be used to prevent cardiovascular disease in women. The objective was to evaluate the changes in lipoprotein subfractions induced by three months of treatment with an epicatechin-enriched cacao supplement. A double-blind, placebo-controlled proof-of-concept study was developed to evaluate the effects of 3 months of treatment with an (-)-epicatechin-enriched cacao supplement on lipoprotein subfractions. The usual screening workshop for postmenopausal women could be insufficient and misleading. Assessing the effect of a (-)-epicatechin-enriched cacao supplement employing a lipoprotein subfractionation profile analysis suggests a decrease in cardiovascular risk. A simple, low-cost, safe (-)-epicatechin-enriched cacao supplement product can improve the cardiovascular risk in postmenopausal women.

Moderate Alcohol Consumption and Lipoprotein Subfractions: A Systematic Review of Intervention and Observational Studies

<h3>Lead Author's Financial Disclosures</h3> T.W. has received a Ph.D. scholarship partly sponsored by Carlsberg Foundation Semper Ardens grant Remaining Ph.D. scholarship sponsored by National Institute of Alcohol Abuse and Alcoholism (NIAAA). <h3>Study Funding</h3> Ph.D. scholarship sponsored in part by a Carlsberg Foundation Semper Ardens grant on biomarkers to L.O.D., and in part by National Institute of Alcohol Abuse and Alcoholism [grant number U10AA025286 to L.O.D.]. <h3>Background/Synopsis</h3> Moderate alcohol consumption is associated with decreased risk of cardiovascular disease and improvement in cardiovascular risk markers, including lipoproteins1, 2, and lipoprotein subfractions. Changes in lipoprotein subclasses could mediate the potential beneficial effects of moderate drinking on cardiovascular health. <h3>Objective/Purpose</h3> This study aimed to systematically review the relationship between moderate alcohol intake, lipoprotein subfractions, and related mechanisms. Secondarily, to investigate whether results differed by study design and subject health status. <h3>Methods</h3> The review followed the PRISMA guidelines. Studies with alcohol intake at doses up to 60 g/d were included from nine scientific databases. Lipoprotein subfractions and related mechanisms were examined. Eligible studies were human and ex vivo studies in all kinds of study designs, populations, and publication years. The last search was performed in March 2021, and clinicaltrials.gov was screened for unpublished literature. Risk of bias was assessed with The Cochrane Collaboration tool for assessing the risk of bias, The Risk of Bias Assessment tool for non-randomized Studies, and The JBI Critical Appraisal Checklist for Analytical Cross-Sectional Studies. <h3>Results</h3> We included 37 intervention trials and 77 observational studies with a total of 20,510 and 104,773 participants, respectively. Most intervention studies provided an alcohol dose between 20 to 40 g per day. Alcohol intake was positively related to all HDL subfractions measured, independent of study design. Studies on the effects of alcohol on LDL and VLDL subfractions were limited, especially intervention studies. However, some studies of varying design found lower levels of small LDL particles, increased LDL particle size, and complex, non-linear relationships to apoB-containing particles. Hypothesis generating results on the associations of alcohol with lipoprotein subfractions defined by the content of the pro-atherogenic apoC-III were also identified. As for the mechanisms investigated, cholesterol efflux capacity and paraoxonase activity were consistently increased. Most studies included healthy subjects or populations of mixed health status. Several studies were graded to have unclear or high risk of bias, and heterogeneous laboratory methods restricted comparability between studies. <h3>Conclusions</h3> Alcohol intake in doses up to 60 g/day can cause changes in lipoprotein subfractions, such as increased HDL subfractions and decreased smaller LDL particles, which may relate to cardiovascular health. Future studies should investigate effects on apoB-containing lipoproteins and novel biomarkers such as HDL subfractions defined by apolipoproteins like apoC-III. This review is registered at http://www.crd.york.ac.uk/prospero/, no.: 98955.

Moderate alcohol consumption and lipoprotein subfractions: a systematic review of intervention and observational studies.

Moderate alcohol consumption is associated with decreased risk of cardiovascular disease (CVD) and improvement in cardiovascular risk markers, including lipoproteins and lipoprotein subfractions. To systematically review the relationship between moderate alcohol intake, lipoprotein subfractions, and related mechanisms. Following PRISMA, all human and ex vivo studies with an alcohol intake up to 60 g/d were included from 8 databases. A total of 17 478 studies were screened, and data were extracted from 37 intervention and 77 observational studies. Alcohol intake was positively associated with all HDL subfractions. A few studies found lower levels of small LDLs, increased average LDL particle size, and nonlinear relationships to apolipoprotein B-containing lipoproteins. Cholesterol efflux capacity and paraoxonase activity were consistently increased. Several studies had unclear or high risk of bias, and heterogeneous laboratory methods restricted comparability between studies. Up to 60 g/d alcohol can cause changes in lipoprotein subfractions and related mechanisms that could influence cardiovascular health. PROSPERO registration no. 98955.

Effects Of Aerobic And Resistance Training On The Lipoprotein Subclass Profile In Type 2 Diabetics

PURPOSE: Type 2 diabetes (T2D) is associated with dysfunctional lipid metabolism in addition to impaired glucose metabolism. Exercise is widely prescribed in the treatment of T2D; however, the effects of exercise on complex lipoprotein traits in T2D are not fully understood. METHODS: Change in lipoprotein subclass profile was examined in 214 patients with T2D from the HART-D cohort. Patients were randomized to 9 months of either control (n=33), aerobic training (AT, n=62), resistance training (RT, n=55), or combination of aerobic and resistance training (AT/RT, n=64). NMR spectroscopy was used to quantify lipoprotein size, total and subclass concentrations of triglyceride rich lipoproteins, low-density lipoproteins, and high-density lipoproteins (TRL-P, LDL-P, and HDL-P respectively). Paired t-tests were used to assess the effects of exercise within each intervention, and general linear models (GLMs) adjusting for group, sex, race, age, baseline BMI, and baseline trait value were used to compare changes in lipoprotein subfractions in exercise groups to changes in control. RESULTS: AT resulted in nominal (p<0.05) changes in small HDL-P (H2 (7.8nm): -0.69 μmol/L p=0.032, H1 (7.4nm): 0.44 μmol/L, p=0.03), and RT increased medium LDL-P (43.89 nmol/L, p=0.002), while AT/RT failed to produce changes in any lipoprotein subclass. Adjusted GLMs revealed the change in H2 HDL-P was less in AT compared control (p=0.01). Additionally, despite no training response in large LDL-P subclass concentration following AT, change in large LDL-P was less in the AT group compared to control (p=0.01). CONCLUSIONS: Overall, exercise training resulted in minimal changes in the lipoprotein subclass profile in patients with T2D. Further studies are needed to elucidate the potential effects of exercise dose on lipoprotein subfractions to improve upon the clinical utility of exercise prescription in the treatment of T2D.

Relationship between resolution of non-alcoholic steatohepatitis and changes in lipoprotein sub-fractions: a post-hoc analysis of the PIVENS trial.

Dyslipidaemia is frequent in non-alcoholic steatohepatitis (NASH); however, it is unclear if improvement in liver histology is associated with favourable changes in cardiovascular disease (CVD) risk. To evaluate the relationship of NASH resolution and lipoprotein subfraction levels, markers of endothelial dysfunction, and macrophage activation. One hundred and seventeen individuals with NASH who participated in the Pioglitazone vs Vitamin E vs Placebo for the Treatment of Nondiabetic Patients with NASH (PIVENS) trial with paired liver biopsies and serum samples available at baseline and after 96weeks of treatment were included. Participants in the PIVENS trials received vitamin E, pioglitazone, or placebo for 96weeks. Lipoprotein subfraction levels, intracellular adhesion molecule 1 (ICAM-1), vascular cellular adhesion molecule 1 (VCAM-1), E-selectin, and sCD163 levels were assessed at baseline and week 96 and their relationship with NASH resolution was examined. Fifty-seven individuals had NASH resolution and 60 individuals did not have resolution of NASH. NASH resolution was associated with favourable changes in lipoprotein subfraction levels compared to those without NASH resolution. Individuals with resolution of NASH had a significantly increased mean peak LDL diameter (ratio of geometric means [96weeks vs baseline] 1.007 vs 0.996, P=0.004), and higher frequency of LDL phenotype A (58% vs 33%, P=0.003) at week 96, after adjustment for relevant co-variates including treatment group. No differences in VCAM, ICAM, E-selectin, or sCD163 levels by NASH resolution were found. NASH resolution is associated with favourable changes in a subset of serum lipoprotein levels. More studies are warranted to understand if these favourable changes are associated with decreased risk of CVD.

Abstract P064: Weight Loss Induced by Healthy Diets Reduces Atherogenic Lipoproteins that Contain ApoC-III Independent of Dietary Macronutrient Content

Background: Weight-loss improves lipid risk factors for cardiovascular disease risk. However, the effect of weight loss on VLDL, LDL and HDL subtypes that contain apoC-III, newly emerging as important predictors of CVD, is not known. Further, the effects of dietary macronutrient composition on changes in apoC-III-containing lipoproteins in the presence of weight loss have not been studied. Methods: The Pounds Lost Trial randomized 811 overweight and obese subjects to four healthful diets that varied in emphasis of unsaturated fat, protein, and carbohydrate for 24 months. A random 50% subsample was selected for analysis of lipoprotein subfractions (~100 per study diet). Plasma samples were collected at baseline and after 24 months and stored at -80C to await analysis. Whole plasma was fractionated first by apoC-III content and then by density (VLDL, IDL+LDL, HDL) to produce 6 subfractions: VLDL with apoC-III, VLDL without apoC-III, IDL+LDL with apoC-III, IDL+LDL without apoC-III, HDL with apoC-III, HDL without apoC-III. Apolipoprotein and lipid concentrations were measured in these subfractions. The primary aim was to determine whether macronutrient content of diets for weight loss influenced changes after weight loss in concentrations and compositions of the 6 lipoprotein subfractions. A secondary analysis determined the relation between amount of weight-loss and change in the lipoproteins, adjusted for baseline BMI, age, race, and sex. Results: On average, the study population had lost 5% of their body weight at 2 years regardless of randomized diet group. Changes in lipoprotein subfractions from baseline to 2 years were similar among the 4 diet groups. Multiple regression analysis determined that degree of weight loss significantly predicted reductions in apoC-III in VLDL, LDL and HDL. For example, a 5% weight loss corresponded to reductions in apoC-III in VLDL of 14% (95% CI: 8.0%, 19.8%), LDL of 5.5% (0.3%, 8.6%), and HDL of 2.2% (0.1%, 4.4%). Weight loss notably predicted a decrease in the apoB concentration of LDL with apoC-III. The concentration of LDL with apoC-III was the strongest predictor of CVD in several cohorts. In contrast, weight loss predicted increases in apoE in VLDL and LDL. ApoE increases the clearance from plasma of VLDL and LDL and reduces the formation of LDL from VLDL. Conclusion: Weight loss achieved through healthful diets reduces apoC-III and atherogenic LDL with apoC-III but increases apoE in apoB-lipoproteins regardless of macronutrient emphasis. These effects on lipoprotein subfractions represent a novel mechanism by which weight loss may reduce cardiovascular disease risk.

LDL-apheresis: indications and clinical experience in a tertiary cardiac centre

To determine the efficacy and safety of liposorber D low-density lipoprotein (LDL) apheresis system in high-risk cardiac patients. Retrospective analysis of 466 treatments undertaken in eight patients with coronary heart disease. Five patients had severe heterozygous familial hypercholesterolaemia (FH), one had severe hypertriglyceridaemia and two were cardiac transplant recipients with FH intolerant to statins. Acute reductions during single sessions and preprocedural long-term changes in lipoprotein subfractions, laboratory safety parameters, adverse events and clinical outcome were recorded. In 352 treatments performed in seven patients, acute reductions averaged 52.8% (standard deviation: 8.61%) for total cholesterol (TC), 61.8% (10.13%) for LDL-cholesterol (LDL-C), 21.1% (9.66%) for high-density lipoprotein cholesterol (HDL-C), 71.1% (median) for lipoprotein (a) [Lp(a)] and 44.5% (14.42%) for triglycerides (p < 0.05). Long-term reductions of TC, LDL-C, Lp(a) and triglycerides by 18.1%, 21.7%, 9.4% (median) and 19.8%, respectively, were achieved. HDL-C was increased by 7.5%. Results from the patient with severe hypertriglyceridaemia were analysed separately because of markedly elevated TC and triglycerides. Technical and clinical complications were mild and showed an incidence of 16.65% and 12.45% respectively. The most common clinical event was transient hypotension (5.8%), whereas vascular access difficulties (11.3%) represented a common technical problem. All patients demonstrated clinical improvement. However, two patients treated via a central line developed septicaemia, resulting in endocarditis in one of them. Liposorber D is a simple, safe and effective modality in reducing atherogenic lipoproteins in dyslipidaemic high-risk cardiac patients. The treatment via an arteriovenous fistula is the preferred vascular access in this type of patient.

PO9-254 AFFINITY OF C-REACTIVE PROTEIN TOWARDS FCGAMMARI IS STRONGLY ENHANCED BY GAMMA-CHAIN

We studied the effects of exercise (primarily running), calorie restriction (dieting), and a low-fat, high-carbohydrate diet on changes in lipoprotein subfractions in moderately overweight men in a randomized controlled clinical trial. After 1 year, complete data were obtained for 39 men assigned to lose weight through dieting without exercise, 37 men assigned to lose weight through dieting with exercise (primarily running), and 40 nondieting sedentary controls. We instructed both diet groups to consume no more than 30% total fat, 10% saturated fat, and 300 mg/d of cholesterol, and at least 55% carbohydrates, and the controls were instructed to maintain their usual food choices. Analytic ultracentrifugation was used to measure changes in plasma lipoprotein mass concentrations. In addition, the absorbance of protein-stained polyacrylamide gradient gels was used as an index of concentrations for five high-density lipoprotein (HDL) sublcasses that have been identified by their particle sizes, ie, HDL3c (7.2 to 7.8 nm), HDL3b (7.8 to 8.2 nm), HDL3a (8.2 to 8.8 nm), HDL2a (8.8 to 9.7 nm), and HDL2b (9.7 to 12 nm). Relative to controls, weight decreased significantly in men who dieted with exercise (net difference ± SE, −3.3 ± 0.4 kg/m2) and in men who dieted without exercise (−2.0 ± 0.4 kg/m2). Dieting with exercise significantly decreased very-low-density lipoprotein (VLDL)-mass concentrations and significantly increased plasma HDL2-mass, HDL3a, HDL2a, and HDL2b relative to both control and dieting without exercise. There were no significant changes in lipoprotein mass and HDL protein for dieters who did not run. Adjustment for weight loss by analysis of covariance eliminated the significant decrease in VLDL-mass and increases in HDL2-mass and HDL2b in men who both increased exercise and dieted. Thus, the addition of exercise to dieting appears to increase HDL2-mass and HDL2b through metabolic processes associated with weight loss, and to increase HDL2a and HDL3a through processes that are independent of weight loss. Previous exercise studies that report changes in HDL that are independent of weight loss may be measuring increases in HDL2a and HDL3a rather than HDL2b.

A Randomized Study Comparing the Effects of a Low‐Carbohydrate Diet and a Conventional Diet on Lipoprotein Subfractions and C‐reactive Protein Levels in Patients With Severe Obesity

To compare the effects of a low-carbohydrate diet and a conventional (fat- and calorie-restricted) diet on lipoprotein subfractions and inflammation in severely obese subjects. We compared changes in lipoprotein subfractions and C-reactive protein levels in 78 severely obese subjects, including 86% with either diabetes or metabolic syndrome, who were randomly assigned to either a low-carbohydrate or conventional diet for 6 months. Subjects on a low-carbohydrate diet experienced a greater decrease in large very low-density lipoprotein (VLDL) levels (difference =-0.26 mg/dL, p = .03) but more frequently developed detectable chylomicrons (44% vs 22%, p = .04). Both diet groups experienced similar decreases in the number of low-density lipoprotein (LDL) particles (difference = -30 nmol/L, p = .74) and increases in large high-density lipoprotein (HDL) concentrations (difference = 0.70 mg/dL, p = .63). Overall, C-reactive protein levels decreased modestly in both diet groups. However, patients with a high-risk baseline level (>3 mg/dL, n = 48) experienced a greater decrease in C-reactive protein levels on a low-carbohydrate diet (adjusted difference = -2 mg/dL, p = .005), independent of weight loss. In this 6-month study involving severely obese subjects, we found an overall favorable effect of a low-carbohydrate diet on lipoprotein subfractions and on inflammation in high-risk subjects. Both diets had similar effects on LDL and HDL subfractions. ( Am J Med. 2004;117:398-405.).

A randomized study comparing the effects of a low-carbohydrate diet and a conventional diet on lipoprotein subfractions and C-reactive protein levels in patients with severe obesity

To compare the effects of a low-carbohydrate diet and a conventional (fat- and calorie-restricted) diet on lipoprotein subfractions and inflammation in severely obese subjects. We compared changes in lipoprotein subfractions and C-reactive protein levels in 78 severely obese subjects, including 86% with either diabetes or metabolic syndrome, who were randomly assigned to either a low-carbohydrate or conventional diet for 6 months. Subjects on a low-carbohydrate diet experienced a greater decrease in large very low-density lipoprotein (VLDL) levels (difference = -0.26 mg/dL, P = 0.03) but more frequently developed detectable chylomicrons (44% vs. 22%, P = 0.04). Both diet groups experienced similar decreases in the number of low-density lipoprotein (LDL) particles (difference = -30 nmol/L, P = 0.74) and increases in large high-density lipoprotein (HDL) concentrations (difference = 0.70 mg/dL, P = 0.63). Overall, C-reactive protein levels decreased modestly in both diet groups. However, patients with a high-risk baseline level (>3 mg/dL, n = 48) experienced a greater decrease in C-reactive protein levels on a low-carbohydrate diet (adjusted difference = -2.0 mg/dL, P = 0.005), independent of weight loss. In this 6-month study involving severely obese subjects, we found an overall favorable effect of a low-carbohydrate diet on lipoprotein subfractions, and on inflammation in high-risk subjects. Both diets had similar effects on LDL and HDL subfractions.

Reductions in Abdominal Adiposity and its Association with Lipoprotein Subfractions

0543 PURPOSE: The purpose of this study was to determine the relationship between changes in abdominal adiposity (AA) with changes in lipid subfractions and particles sizes in overweight adults undergoing 16-months of supervised, verified exercise with an ad libitum diet. METHODS: Subjects (n = 52, age 18–35, BMI ≥ 25) were randomly assigned to non-exercise control (women, n = 12, men, n = 12) or exercise (women, n = 18, men, n = 10) groups. Aerobic exercise progressed to 45 minutes·day−1, 5 days·week−1 over 6 months and was maintained for an additional 10 months. Controls maintained their normal physical activity. AA was measured by computed topography at baseline and 16-months. Lipid subfractions and particles sizes were isolated from fasting blood samples by nuclear magnetic resonance at baseline and 16-months. RESULTS: For men in the control group there was a significant correlation between changes in visceral abdominal fat (VAF) (r = 0.62), subcutaneous abdominal fat (r = 0.80), and total abdominal fat (r = 0.75) with changes in medium very low density lipoprotein with no other significant correlations. Changes in VAF with change in small high density lipoprotein (r = 0.66) was significant for the control women, with no other significant correlations occurring. There were no significant correlations between changes in lipoprotein subfractions and particle sizes with any measure of AA in the exercising men or women. CONCLUSION: We conclude that reductions in AA may not correspond to improvements in lipid subfractions or particles sizes in young adults participating in long-term exercise. Therefore, other factors other than a reduction in AA may contribute to reducing metabolic risk factors in young adults.

Application of the small-angle X-ray scattering technique for estimating structural changes in lipoprotein subfractions

Application of the small-angle X-ray scattering technique for estimating structural changes in lipoprotein subfractions

Effects of low-fat diet, calorie restriction, and running on lipoprotein subfraction concentrations in moderately overweight men

We studied the effects of exercise (primarily running), calorie restriction (dieting), and a low-fat, high-carbohydrate diet on changes in lipoprotein subfractions in moderately overweight men in a randomized controlled clinical trial. After 1 year, complete data were obtained for 39 men assigned to lose weight through dieting without exercise, 37 men assigned to lose weight through dieting with exercise (primarily running), and 40 nondieting sedentary controls. We instructed both diet groups to consume no more than 30% total fat, 10% saturated fat, and 300 mg/d of cholesterol, and at least 55% carbohydrates, and the controls were instructed to maintain their usual food choices. Analytic ultracentrifugation was used to measure changes in plasma lipoprotein mass concentrations. In addition, the absorbance of protein-stained polyacrylamide gradient gels was used as an index of concentrations for five high-density lipoprotein (HDL) sublcasses that have been identified by their particle sizes, ie, HDL 3c (7.2 to 7.8 nm), HDL 3b (7.8 to 8.2 nm), HDL 3a (8.2 to 8.8 nm), HDL 2a (8.8 to 9.7 nm), and HDL 2b (9.7 to 12 nm). Relative to controls, weight decreased significantly in men who dieted with exercise (net difference ± SE, −3.3 ± 0.4 kg/m 2) and in men who dieted without exercise (−2.0 ± 0.4 kg/m 2). Dieting with exercise significantly decreased very-low-density lipoprotein (VLDL)-mass concentrations and significantly increased plasma HDL 2-mass, HDL 3a, HDL 2a, and HDL 2b relative to both control and dieting without exercise. There were no significant changes in lipoprotein mass and HDL protein for dieters who did not run. Adjustment for weight loss by analysis of covariance eliminated the significant decrease in VLDL-mass and increases in HDL 2-mass and HDL 2b in men who both increased exercise and dieted. Thus, the addition of exercise to dieting appears to increase HDL 2-mass and HDL 2b through metabolic processes associated with weight loss, and to increase HDL 2a and HDL 3a through processes that are independent of weight loss. Previous exercise studies that report changes in HDL that are independent of weight loss may be measuring increases in HDL 2a and HDL 3a rather than HDL 2b.

Dyslipidemia and ischemic heart disease mortality among men and women with diabetes.

We investigated whether the greater increased risk of ischemic heart disease mortality associated with diabetes among women compared with men could be explained by their more pronounced lipoprotein abnormalities. Seventy-six men and 45 women with diabetes and 327 men and 496 women without diabetes were followed for an average of 16 years in a population-based study. Cox proportional hazards models were used to determine the relative hazard of ischemic heart disease mortality for changes in lipoprotein subfractions after adjustment for age, hypertension, obesity, smoking, exercise, alcohol consumption, and estrogen use (among women). The relative hazard of ischemic heart disease mortality among diabetic women was 1.76 (P = .10) for a 10-mg/dL decrement in high-density lipoprotein cholesterol (HDL-C) and 3.13 (P = .01) for a 1-U increment in log very-low-density lipoprotein cholesterol (VLDL-C). The risk of ischemic heart disease mortality among diabetic women relative to nondiabetic women for an HDL-C level of 50 mg/dL and a log(e) VLDL-C of 3 (about 20 mg/dL) were 4.1 and 3.4, respectively (P < .05). These lipoprotein changes were not associated with ischemic heart disease mortality among men or among nondiabetic women. Excess ischemic heart disease mortality among diabetic women is partially explained by deleterious levels of HDL-C and VLDL-C. HDL-C levels of < or = 50 mg/dL and VLDL-C levels of > or = 20 mg/dL appear to predict ischemic heart disease mortality among these women and may help identify women who would benefit most from intervention.

Changes in lipoprotein subfractions during diet-induced and exercise-induced weight loss in moderately overweight men.

We studied separately the effects of weight loss by calorie restriction (dieting) and by calorie expenditure (primarily, running) on lipoprotein subfraction concentrations in sedentary, moderately overweight men assigned at random into three groups as follows: exercise without calorie restriction (n = 46), calorie restriction without exercise (n = 42), and control (n = 42). Plasma lipoprotein mass concentrations were measured by analytic ultracentrifugation for flotation rates (F0(1.20), S0f) within high density lipoprotein (HDL) (F0(1.20) 0-9), low density lipoprotein (LDL) (S0f 0-12), intermediate density lipoprotein (IDL) (S0f 12-20), and very low density lipoprotein (VLDL) (S0f 20-400) particle distributions. Particle diameter and flotation rate of the most abundant LDL species were determined by nondenaturing polyacrylamide gradient gel electrophoresis and analytic ultracentrifugation, respectively. During the 1-year trial, the exercisers ran (mean +/- SD) 15.6 +/- 9.1 km/wk, and the dieters ate 340 +/- 71 fewer kilocalories per day than at baseline. Total body weight was reduced significantly more in dieters (-7.2 +/- 4.1 kg) and exercisers (-4.0 +/- 3.9 kg) than controls (0.6 +/- 3.7 kg). As compared with mean changes in controls, the exercisers and dieters significantly increased HDL2 mass (48.6% and 47.1%, respectively), decreased VLDL mass (-23.9% and -25.5%), and increased LDL peak particle diameter (2.4 and 3.2 A). When adjusted to an equivalent change in body mass index by analysis of covariance, 1) exercise-induced and diet-induced weight loss produced comparable mean changes in the mass of small LDL and VLDL, and in LDL peak particle diameter; 2) the exercisers versus control group difference in HDL2 was attributed to the exercisers' reduced body mass index; and 3) HDL2 increased significantly less in dieters than in exercisers. In dieters, low calorie intake might mitigate the effects of weight loss on HDL2.