Influence of inoculation site of combined oil-adjuvanted vaccine on the antibody response in chickens

In this study, we evaluated the relationship between resistance to insulin-mediated glucose disposal and hematocrit (Hct) and hemoglobin (Hgb) concentrations in 150 normal, healthy volunteers: 100 men and 50 women. Insulin resistance was defined as the steady-state plasma glucose (SSPG) concentration at the end of a 180-minute infusion of somatostatin, insulin, and glucose. Since the steady-state plasma insulin (SSPI) concentrations are similar in all individuals, the SSPG concentrations provide a direct measure of insulin resistance: the higher the SSPG, the more insulin-resistant the subject. The results indicated that SSPG was significantly (P < .001) related to Hct and Hgb in both men and women, with correlation coefficients (r) ranging from 0.38 to 0.43. A series of other variables were also related to Hct and Hgb, including blood pressure, plasma glucose and insulin responses to oral glucose, and plasma triglyceride and high-density lipoprotein (HDL) concentrations. When multiple regression analysis was used to evaluate these relationships, the only variables that were consistently found to be associated with Hct and Hgb were insulin resistance and plasma insulin response to oral glucose. Thus, these results suggest that Hct and Hgb concentrations be added to the cluster of variables related to insulin resistance and compensatory hyperinsulinemia.     

Schizophrenia and delusional disorder in older age: community prevalence, incidence, comorbidity, and outcome

Obesity is associated with dyslipidaemia characterised by increased fasting triglyceride and decreased high-density lipoprotein (HDL) concentrations. Causes for obesity-associated dyslipidaemia include insulin resistance, excessive caloric intake, increased free fatty acid production and disturbances in the counter-regulatory hormones. We examined the relationships between lipid parameters and obesity before and after adjustment of insulin resistance in 902 Hong Kong Chinese men. After adjustment for age, smoking and insulin resistance, increasing body mass index (BMI) and waist-to-hip ratio (WHR) remained closely associated with increased concentrations of triglyceride and apolipoprotein B (apo B), increased ratios between low-density lipoprotein (LDL) and HDL (LDL/HDL), and that between apo B and LDL (apo B/LDL), increased fasting and 2-h plasma glucose and insulin, as well as decreased concentrations of HDL, HDL2 and apolipoprotein A-I (apo A-I). On stepwise multiple regression analysis using age, BMI, WHR, insulin resistance and fasting plasma glucose as independent variables, BMI and WHR were the major determinants for the variance of triglyceride, HDL and its subfractions, LDL/HDL, apo B and apo B/LDL. Age was the most important predictor for total cholesterol and LDL. Insulin resistance only explained less than 1% of the variance in triglyceride and apo B. This was compared to a variance between 10 and 16% in these parameters as explained by BMI and/or WHR. In conclusion, obesity is associated with dyslipidaemia in Chinese men, characterised by increased plasma triglyceride, apo B, LDL/HDL, apo B/LDL, and decreased HDL, HDL2 and apo A-I concentrations. Obesity independent of insulin resistance, in particular central adiposity as reflected by increased WHR, was the most important independent variable for many of these lipid abnormalities. Our results emphasised the multifactorial linkage between obesity and dyslipidaemia.     

Effects of a quick-release form of bromocriptine (Ergoset) on fasting and postprandial plasma glucose, insulin, lipid, and lipoprotein concentrations in obese nondiabetic hyperinsulinemic women

OBJECTIVE: To assess the effect on various aspects of carbohydrate and lipid metabolism of administering a quick-release formulation of bromocriptine (Ergoset) to obese, nondiabetic, hyperinsulinemic women. RESEARCH DESIGN AND METHODS: Hourly concentrations of prolactin, glucose, insulin, free fatty acid (FFA), and triglyceride were measured for 24 h before and after approximately 8 weeks of treatment with Ergoset. In addition, fasting lipid and lipoprotein concentrations and the steady-state plasma glucose (SSPG) concentration in response to a continuous infusion of somatostatin, insulin, and glucose were determined before and after Ergoset administration. RESULTS: Circulating prolactin concentrations were dramatically decreased (P < 0.001) following treatment, associated with a significant fall (P < 0.05) in 24-h-long plasma glucose, FFA, and triglyceride concentrations. Neither circulating plasma insulin concentrations nor the ability of insulin to mediate glucose disposal changed with treatment. Finally, fasting total cholesterol fell (P < 0.05) and the ratio of total to HDL cholesterol decreased (P = 0.06) in association with Ergoset treatment. CONCLUSIONS: The fact that significant metabolic improvement was seen in the obese nondiabetic hyperinsulinemic women studied suggests that Ergoset could be of therapeutic benefit in clinical conditions of hyperglycemia and/or dyslipidemia.     

Insulin sensitivity in familial hypercholesterolemia

Insulin resistance is found in association with obesity, non-insulin-dependent diabetes mellitus, and essential hypertension, which are all risk factors for atherosclerotic cardiovascular disease. Furthermore, hyperinsulinemia has been reported in familial combined hyperlipoproteinemia and endogenous hypertriglyceridemia. Finally, relatively high serum triglyceride and low high-density lipoprotein (HDL) cholesterol concentrations invariably accompany hyperinsulinemia. Whether insulin sensitivity is affected by the isolated presence of high levels of serum low-density lipoprotein (LDL) cholesterol has not been clearly established. We studied 13 subjects with heterozygous familial hypercholesterolemia (FHC) and 15 normocholesterolemic subjects selected to be free of any other known cause of insulin resistance. Thus FHC patients and controls had normal body weight and fat distribution, glucose tolerance, blood pressure, and serum triglyceride and HDL cholesterol concentrations, but were completely separated on plasma LDL cholesterol concentrations (6.05 +/- 0.38 v 3.27 +/- 0.15 mmol/L, P < .0001). Fasting plasma levels of glucose, insulin, free fatty acids (FFA), and potassium and fasting rates of net carbohydrate and lipid oxidation were superimposable in the two study groups. During a 2-hour euglycemic (approximately 5 mmol/L) hyperinsulinemic (approximately 340 pmol/L) clamp, whole-body glucose disposal rates averaged 30.4 +/- 2.3 and 31.1 +/- 3.0 mumol.kg-1 x min-1 in FHC and control subjects, respectively (P = 0.88). The ability of exogenous hyperinsulinemia to stimulate carbohydrate oxidation and energy expenditure and suppress lipid oxidation and plasma FFA and potassium levels was equivalent in FHC and control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ambulatory blood pressure and Holter monitoring of emergency physicians before, during, and after a night shift

BACKGROUND: Patients with a mutation in the LDL receptor gene (familial hypercholesterolemia, or FH) are characterized by substantial elevations in plasma LDL cholesterol and are at higher risk of developing coronary artery disease (CAD). Correlates of abdominal obesity may also contribute to the risk of ischemic cardiac events. Whether the hyperinsulinemic-insulin-resistant state of abdominal obesity affects coronary atherosclerosis among FH patients has not been determined. METHODS AND RESULTS: The relation of abdominal adiposity and hyperinsulinemia to angiographically assessed CAD was evaluated in a sample of 120 French Canadian men aged <60 years who were heterozygotes for FH and in a group of 280 men without FH. In the present study, the risk of CAD associated with abdominal obesity, as estimated by the waist circumference, was largely dependent on the concomitant variation in plasma lipoprotein and insulin concentrations. In contrast, the association between fasting insulin and CAD was independent of variations in waist girth, triglyceride, HDL, and apolipoprotein B concentrations (odds ratio, 1.86; P=.0005). However, the most substantial increase in the risk of CAD was observed among abdominally obese (waist circumference >95 cm) and hyperinsulinemic FH patients (odds ratio, 12.9; P=.0009). This increase in risk remained significant even after adjustment for LDL cholesterol or apolipoprotein B concentrations. CONCLUSIONS: Results of the present study provide support for the notion that the hyperinsulinemic-insulin-resistant state of abdominal obesity is a powerful predictor of CAD in men, even in a group of patients with raised LDL cholesterol concentrations due to FH.     

Effect of pravastatin treatment on glucose, insulin, and lipoprotein metabolism in patients with hypercholesterolemia

Treatment of patients with type IIA hyperlipoproteinemia (HLP) with pravastatin for 3 months led to significant decreases (p < 0.001) in total cholesterol (7.18 +/- 0.30 to 5.75 +/- 0.30 mmol/L), LDL cholesterol (5.56 +/- 0.33 to 4.02 +/- 0.32 mmol/L), and ratio of total cholesterol to HDL cholesterol (6.5 +/- 0.4 to 4.6 +/- 0.4). Decreases of a similar magnitude were also seen in patients with type IIB HLP. Plasma glucose and insulin concentrations after an oral glucose load and from 8 AM to 4PM in response to meals were higher in patients with Type IIB HLP, who also had higher steady-state plasma glucose concentrations after an infusion of somatostatin, insulin, and glucose (12.4 +/- 1 vs 5.5 +/- 0.8 mmol/L, p < 0.001). Because steady-state plasma insulin concentrations were similar in both groups, patients with type IIB HLP were relatively insulin resistant. Furthermore, day-long plasma glucose concentrations and insulin resistance were modestly, but significantly (p < 0.01), greater after treatment in both groups. In conclusion, LDL cholesterol metabolism improved in hypercholesterolemic subjects treated with pravastatin, but the hypertriglyceridemia, insulin resistance, relative glucose intolerance, and hyperinsulinemia present in patients with type IIB HLP either did not improve with treatment or was somewhat worse.     

Hyperinsulinemia and insulin resistance are associated with multiple abnormalities of lipoprotein subclasses in glucose-tolerant relatives of NIDDM patients. Botnia Study Group

We studied the subclasses of plasma lipoproteins in normolipidemic, glucose-tolerant male relatives of noninsulin dependent diabetic patients (NIDDM), who represented either the lowest (n = 14) or the highest (n = 18) quintiles of fasting plasma insulin. The higher plasma triglyceride level in the high insulin group (1.61 mmol/l vs. 0.87 mmol/l, P < 0.001) was due to multiple differences in triglyceride-rich lipoproteins. The concentrations of larger VLDL1, smaller VLDL2 particles, and IDL particles were 3.8-fold, 2.5-fold, and 1.5-fold higher, respectively, in the high insulin group than in the low insulin group (P < 0.01 or less). In addition, hyperinsulinemic subjects had VLDL1, VLDL2, and IDL particles enriched in lipids and poor in protein. The lower plasma HDL cholesterol level in the high insulin group (1.20 mmol/l vs. 1.44 mmol/l, P < 0.01) compared to the low insulin group was a consequence of a 27% reduction of HDL2a concentration (P < 0.05) and a significantly reduced percentage of cholesterol in HDL3a, HDL3b, and HDL3c subclasses. On the other hand, the percentages of triglycerides in HDL2b, HDL2a, HDL3a, and HDL3b subclasses were 76%, 79%, 61%, and 50% higher, respectively, in the high insulin group than in the low insulin group (P < 0.01 or less). In the combined group, the concentration of VLDL1 and VLDL2 correlated positively with the concentrations of LDL2 and LDL3 and negatively with HDL2b and HDL2a subclasses (P < 0.05 or less). In conclusion, normolipidemic, glucose-tolerant but hyperinsulinemic relatives of NIDDM patients have qualitatively similar lipoprotein abnormalities as NIDDM patients. These abnormalities are not observed in insulin-sensitive relatives, suggesting that they develop in concert with insulin resistance.     

Cutaneous reactions at the site of post-infection gp160 vaccination therapy in HIV-1+ patients. Military Medical Consortium for the Advancement of Military Medicine

OBJECTIVES: To define the pathophysiologic characteristics of patients at high risk for coronary heart disease due to an increased ratio of total cholesterol (TC) to high density lipoprotein-cholesterol (HDL-C). DESIGN: Cross-sectional. SETTING: Clinical Research Center. SUBJECTS: One hundred-20 healthy, non-diabetic, normotensive, volunteers were screened for this study. From this pool, 40 individuals (20 females and 20 males) with the highest and the lowest TC/HDL-C ratios were selected for comparison. MAIN OUTCOME MEASURES: Values for body mass index (BMI), ratio of waist to hip girth (WHR), and blood pressure were obtained on all patients. In addition, measurements were made of fasting lipid and lipoprotein concentrations, plasma glucose and insulin responses to an oral glucose challenge, and insulin resistance as assessed by the insulin suppression test. RESULTS: Age, BMI, and WHR were the same in the two groups. However, the group with a high TC/HDL-C ratio had higher (P < 0.05) systolic and diastolic blood pressures. In addition, patients with a high TC/HDL-C ratio had significantly higher (P < 0.001) very low density (VLDL) and low density lipoprotein (LDL)-cholesterol concentrations and lower HDL-cholesterol concentrations, with significant (P < 0.001) correlations between the TC/HDL-C ratio and VLDL (r = 0.60), LDL (r = 0.54), and HDL (r = -0.73) cholesterol concentrations. Patients with a high TC/HDL-C ratio were also significantly (P < 0.05-0.001) more insulin resistant, glucose intolerant with a greater plasma insulin response to oral glucose, and hypertriglyceridemic. CONCLUSIONS: The results indicate that an increase in LDL-cholesterol concentration is not necessarily the major contributor to a high ratio of TC/HDL-C. Furthermore, individuals with this epidemiologic designation are insulin resistant, and liable to all the other abnormalities associated with this metabolic defect.     

Adverse change in low-density lipoprotein subfractions profile with oestrogen-only hormone replacement therapy

In a prospective longitudinal study in 17 women, we investigated the effects of surgical menopause and subsequent oestrogen-only hormone replacement therapy (HRT) on plasma concentrations of total cholesterol, HDL cholesterol, LDL cholesterol, triglyceride and LDL subfractions profile. Plasma LDL is a heterogeneous population of particles of varying size, density and chemical composition. The predominance of small LDL particles is a newly-recognized risk factor for coronary artery disease. The LDL score is used to describe LDL subfractions profile and the greater the score, the higher the proportion of small LDL particles. Six weeks after hysterectomy and bilateral oopherectomy, total cholesterol and triglyceride concentrations were significantly increased (p < 0.01) as well as the LDL score (p < 0.05). After 6 weeks of oestrogen-only HRT, total cholesterol concentration was significantly lower and HDL cholesterol concentration significantly higher than before the treatment (p < 0.05). At the same time, mean LDL score significantly increased and in none of the women did LDL subfractions profile change favourably.     

Strobilurin M, tetrachloropyrocatechol and tetrachloropyrocatechol methyl ether: new antibiotics from a Mycena species

OBJECTIVE: To describe lipid and lipoprotein perturbations in gestational diabetes mellitus (GDM) and to examine the potential consequences--e.g, increased birth weight and increased placental lipid transfer. STUDY DESIGN: Maternal and cord free fatty acids (FFAs) and total, very low density lipoprotein (VLDL), low density lipoprotein (LDL), high density lipoprotein (HDL) (and maternal HDL2 and HDL3), triglyceride (TG), and cholesterol and dietary intake were determined for women with diet-treated GDM and for healthy pregnant women with normal glucose tolerance. RESULTS: Women with GDM had higher hemoglobin A1c than controls, while body weight gain was significantly lower for women with GDM as compared to controls. Plasma and lipoprotein TG concentrations were greater for women with GDM, and although plasma FFAs were higher in women with GDM versus controls, the difference was not significant. No differences were observed between groups with respect to maternal plasma or lipoprotein cholesterol. Cord plasma and lipoprotein lipids were similar between groups; with the exception of VLDL + LDL TG, which was lower in women with GDM. In controls, there were significant correlations between maternal plasma TG and cord FFAs; maternal HDL2 cholesterol and cord plasma cholesterol; and maternal plasma TG, maternal HDL2 cholesterol, cord FFAs, and infant birth weight. In GDM, maternal plasma cholesterol and cord VLDL + LDL cholesterol correlated. There were no significant correlations between maternal or cord lipids and infant birth weight in women with GDM. CONCLUSION: Hypertriglyceridemia, rather than hypercholesterolemia, is a feature of GDM. However, elevations in maternal plasma and lipoprotein TGs in women with GDM were not related to fetal lipid concentrations or infant birth weight.     

Relationship between insulin-mediated glucose disposal by muscle and adipose tissue lipolysis in healthy volunteers

The present study was performed in 17 nondiabetic subjects and was initiated to determine whether enhanced adipose tissue lipolysis, either basal or catecholamine induced (isoproterenol), and/or resistance to insulin inhibition of isoproterenol-stimulated lipolysis were correlated with resistance to insulin-mediated glucose disposal by muscle. Insulin-mediated glucose disposal was assessed by determining the steady state plasma glucose (SSPG) concentration during the insulin suppression test [180 min infusion of somatostatin (350 micrograms/h), insulin (25 mU/m2min), and glucose (240 mg/m2.min)]. On another occasion, plasma FFA and glycerol concentrations were determined at the end of 3 sequential infusion periods (IP): IP1, somatostatin (350 micrograms/h) plus basal insulin replacement (5 mU/m2.min); IP2, somatostatin (350 micrograms/h), insulin (5 mU/m2.min), and isoproterenol (270 ng/m2.min); and IP3, somatostatin (350 micrograms/h), isoproterenol (270 ng/m2.min), and insulin (10 mU/m2.min). SSPG concentrations correlated with FFA concentrations during all 3 infusion periods after adjustment for age, gender, body mass index, insulin concentration, and ratio of waist to hip girth (IP1:r = 0.61; P < 0.03; IP2: r = 0.70; P < 0.01; IP3: r = 0.65; P < 0.02). Correlations between SSPG and glycerol concentrations were also highly statistically significant (IP1: r = 0.62; P < 0.03; IP2: r = 0.65; P < 0.02; IP3: r = 0.70; P < 0.01). These results demonstrate for the first time that plasma FFA and glycerol concentrations are increased commensurate with the degree of resistance to insulin-mediated glucose disposal at a basal insulin level, in response to isoproterenol stimulation, and after insulin inhibition of isoproterenol-stimulated lipolysis.     

Metabolic abnormalities following heart transplantation in patients with idiopathic cardiomyopathy

The purpose of this study was to evaluate the risk factors for coronary artery disease associated with initiation of immunosuppressive therapy in patients with a pre-heart transplant diagnosis of idiopathic cardiomyopathy. This study was performed in 15 consecutive patients, mean +/- SEM age of 39 +/- 2 years, with a pre-operative diagnosis of idiopathic cardiomyopathy, who underwent cardiac transplantation at the Tri-Services General Hospital, Taipei, Taiwan, from July 1992 to June 1993. All patients were treated with cyclosporine, azathioprine and prednisolone, and the following measurements were performed prior to hospital discharge (mean +/- SEM) 36 +/- 3 days after successful transplantation: 1) fasting plasma lipid and lipoprotein concentrations; 2) plasma glucose and insulin concentrations in response to a 75 g oral glucose challenge; and 3) steady-state plasma insulin (SSPI) and glucose (SSPG) concentrations in response to a continuous infusion of somatostatin, insulin, and glucose. Since the SSPI concentrations are similar in all individuals, the SSPG concentrations provide an estimate of the ability of insulin to stimulate glucose disposal. Only six of the patients had a normal oral glucose tolerance test and the following diagnoses were found in the remaining nine patients: not diagnised (n = 3), impaired glucose tolerance (n = 4), and non-insulin-dependent diabetes (n = 2). Plasma lipid and lipoprotein concentrations were also frequently abnormal in the heart transplant patients; eight of the 15 patients had a plasma cholesterol > 5 mmol/l, nine had a high density lipoprotein (HDL)-cholesterol concentration < 1 mmol/l, and nine had a ratio of total to HDL-cholesterol > 5.0. Finally, the SSPG concentration was greater than 11.0 mmol/l in eight of the 15 patients, a value rarely exceeded in healthy volunteers. In conclusion, significant metabolic abnormalities were present at discharge in patients who had undergone successful cardiac transplantation for idiopathic cardiomyopathy. These metabolic abnormalities were probably caused by the use of immunosuppressive drugs. Given the magnitude of these changes, it would seem prudent to initiate therapeutic programs in patients with cardiac transplants that are not simply aimed at preventing rejection, but also address the metabolic abnormalities associated with the immunosuppressive agents used to prolong allograft survival.     

Relationship between plasma LDL concentrations during treatment with pravastatin and recurrent coronary events in the Cholesterol and Recurrent Events trial

BACKGROUND: Although LDL lowering has been shown to reduce recurrent coronary events in patients with coronary heart disease, little direct information is available on the extent of LDL lowering required to achieve this outcome. METHODS AND RESULTS: The Cholesterol and Recurrent Events (CARE) trial compared pravastatin and placebo in patients who had experienced myocardial infarction (MI) who had average concentrations of total cholesterol <240 mg/dL (baseline mean, 209 mg/dL) and LDL cholesterol (LDL) 115 to 174 mg/dL (mean, 139 mg/dL). Pravastatin reduced coronary death or recurrent MI by 24%. In multivariate analysis, the LDL concentration achieved during follow-up was a significant, although nonlinear, predictor of the coronary event rate (P=.007), whereas the extent of LDL reduction was not significant, whether expressed as an absolute amount (P=.97) or a percentage (P=.76). The coronary event rate declined as LDL decreased during follow-up from 174 to approximately 125 mg/dL, but no further decline was seen in the LDL range from 125 to 71 mg/dL. In multivariate analysis, triglyceride but not HDL concentrations during follow-up were weakly but significantly associated with the coronary event rate. CONCLUSIONS: The LDL concentrations achieved during treatment with pravastatin or placebo were associated with reduction in coronary events down to an LDL concentration of approximately 125 mg/dL. LDL concentrations <125 mg/dL during treatment were not associated with further benefit. Absolute or percentage reduction in LDL had little relationship to coronary events.     

Increases in dietary cholesterol and fat raise levels of apoprotein E-containing lipoproteins in the plasma of man

Previous studies from this laboratory have determined that diets containing the usual amounts of fat to which are added 750-1500 mg/day cholesterol elevate the plasma cholesterol concentration by variable amounts, depending upon the ratio of polyunsaturated to saturated fatty acids (P/S ratio) of the diet. Diets with P/S ratios of 0.25-0.4 are accompanied by elevations of low density lipoprotein (LDL) cholesterol, whereas diets with a P/S ratio of 2.5 produce no significant changes in cholesterol levels. On the low P/S ratio diets, the structure, composition, and interaction with cultured fibroblasts of LDL are not significantly changed. Plasma high density lipoprotein (HDL) cholesterol levels remain constant, but HDL2 increase relative to HDL3. In the present study, not only dietary cholesterol but also total dietary fat was altered. Six normal young men were fed a basal diet consisting of 18% protein, 51% carbohydrate, and 30% fat, containing 250 mg/day cholesterol. After 2 weeks, an experimental diet consisting of 18% protein, 42% carbohydrate, and 39% fat, containing 1760 mg/day cholesterol, was fed for 4 weeks. The P/S ratios of both diets were about 0.4. Plasma samples were taken twice during each dietary period from 12- to 14-h-fasted subjects and analyzed for their contents of lipoprotein lipids. Plasma levels of LDL and HDL cholesterol increased by 30 and 13 mg/dl, respectively; total and very low density lipoprotein (VLDL) triglyceride concentrations were unaltered. The plasma concentrations of apoproteins (apo) B, E. and A-I, but not A-II, were elevated. Plasma samples also were studied by zonal ultracentrifugation, gel permeation column chromatography, and Pevikon electrophoresis. Although on zonal ultracentrifugation the total concentrations of LDL were increased, the flotation properties and chemical compositions of LDL were not changed. By contrast, HDL2 and HDL3L concentrations increased, and HDL2 became enriched with cholesteryl esters. On gel permeation chromatography, with the subjects on the basal diet, plasma cholesterol eluted in two peaks, corresponding to LDL and HDL. The sizes of the peaks increased on the experimental diet. ApoE eluted in two peaks: one at the leading edge of LDL (corresponding to VLDL or IDL) and the other in the area between LDL and HDL, corresponding to HDLC. On the experimental diet, the apoE peak between LDL and HDL increased. On Pevikon electrophoresis apoE migrated between the LDL and HDL bands. This apoE peak was increased on the experimental diet. These findings suggest that increasing the concentrations of both dietary cholesterol and total fat can increase the levels of plasma LDL, HDL2, and HDLC in fasting normal subjects. Thus, the concentrations of some putatively atherogenic as well as antiatherogenic lipoproteins increased in plasma, and the apparent paradox between the epidemiological and metabolic behaviors of some lipoproteins remains. Clearly, more work is needed to resolve the roles of various lipoproteins in plasma in atherosclerosis.     

Dangerousness: a mutating concept passes through the literature

OBJECTIVE: To evaluate whether hyperfibrinogenemia represents a component of the metabolic syndrome. RESEARCH DESIGN AND METHODS: A cross-sectional study was conducted on the relation between fibrinogen and the metabolic syndrome in a working population of 1,252 nondiabetic men, aged 35-64 years, randomly selected among all men participating in a health screening. We measured anthropometric characteristics, blood pressure, fasting plasma fibrinogen, cholesterol (total, LDL, and HDL), triglycerides, glucose, and insulin. Individuals with two or more metabolic abnormalities (defined as being in the highest quartile of the distribution of diastolic blood pressure, plasma glucose, or triglycerides or being in the lowest quartile of HDL cholesterol) were considered to have the metabolic syndrome. RESULTS: Age-adjusted fibrinogen levels correlated significantly with BMI, waist-to-hip ratio, systolic and diastolic blood pressure, plasma total cholesterol, LDL cholesterol, triglycerides, insulin, and HDL cholesterol (inversely). Subjects with the metabolic syndrome had significantly higher plasma fibrinogen levels than those without (285.1 +/- 1.9 vs. 300.2 +/- 3.0 mg/dl, mean +/- SE, P = 0.0001). Plasma fibrinogen concentrations and the prevalence of hyperfibrinogenemia (defined as > or = 350 mg/dl) increased progressively from 279 to 307 mg/dl (P = 0.0001) and from 9 to 22% (P = 0.0024), respectively, across categories with an increasing number of metabolic disorders characterizing the syndrome (only one, any two, three or more). In multivariate analyses, both plasma insulin and the metabolic syndrome were significantly and independently associated with plasma fibrinogen. CONCLUSIONS: The finding suggests that hyperfibrinogenemia may be considered a component of the metabolic syndrome. This may also explain the increased cardiovascular risk associated with hyperinsulinemia/insulin resistance.     

alpha-Tocopherol concentrations in plasma but not in lipoproteins fluctuate during the menstrual cycle in healthy premenopausal women

Because premenopausal women experience cyclic fluctuations of plasma carotenoids and their lipoprotein carriers, it was hypothesized that plasma alpha-tocopherol (A-T) fluctuates by phase of the menstrual cycle. Twelve free-living women, with a confirmed ovulatory cycle, were given a controlled diet for two consecutive menstrual cycles. Blood was drawn during the menses, early follicular, late follicular and luteal phases to simultaneously measure serum hormones, plasma lipoproteins and A-T concentrations, and A-T distribution in the lipoprotein fractions. Plasma A-T concentrations were significantly lower during menses than during the luteal phase by approximately 12% in each controlled diet cycle (P < 0.001). Adjustment for serum cholesterol and triglyceride concentrations did not alter these findings. The distributions of A-T in lipoprotein cholesterol fractions were not significantly different by menstrual phase. From 61 to 62% of A-T was concentrated in the LDL fraction, with another 9-14% in HDL2, 17-22% in HDL3 and the remaining 6-8% in VLDL+ IDL. There were no significant differences in lipoprotein cholesterol fractions by menstrual phase, except for a significant increase (P = 0.03) in HDL2 cholesterol from the early follicular to the late follicular phase. Spearman rank correlations from data during the second controlled diet month showed A-T in HDL2 in the late follicular phase was positively correlated with HDL cholesterol in the early follicular (r = 0.88), late follicular (r = 0.86) and luteal phases (r = 0.86) and with luteal apolipoprotein (ApoA-1) level (r = 0.90), and luteal HDL2 cholesterol (r = 0.83). A-T in HDL3 in the early follicular phase was negatively correlated with HDL2 cholesterol (r = -0.96) and ApoA-1 (r = -0.85), whereas luteal A-T in HDL3 was correlated with luteal HDL3 cholesterol (r = -0.79). Late follicular A-T in VLDL was positively correlated with early follicular HDL3 cholesterol and late follicular HDL3 cholesterol (r = 0.83). Fluctuations of A-T concentrations by phase of the menstrual cycle should be taken into consideration in future research concerning premenopausal women and the risk of chronic disease.     

Modifications in high-density lipoprotein lipid composition and structure alter the plasma distribution of free and liposomal annamycin

Recent studies have shown that changes in lipoprotein cholesterol and triglyceride concentration alters the plasma distribution of free (Ann.) and liposomal annamycin (LAnn) and that the majority of Ann. is associated with high-density lipoproteins (HDL) following the incubation in plasma of LAnn. To demonstrate that alterations in HDL lipid composition and HDL structure may influence the plasma distribution of Ann. and LAnn, Ann. and LAnn (20 micrograms/mL) were incubated in plasma pretreated with dithionitrobenzoate (DTNB, a compound which inhibits the conversion of free cholesterol to esterified cholesterol) 18 h prior to the experiment or in untreated plasma for 60 min at 37 degrees C. In addition, Ann. and LAnn were co-incubated with DTNB in plasma for 60 min at 37 degrees C. Following incubation the plasma was separated into its HDL, low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL), and lipoprotein-deficient plasma (LPDP) fractions by ultracentrifugation and assayed for Ann. by fluorimetry. The HDL plasma cholesterol:triglyceride concentration ratio was significantly decreased following 18 h of DTNB pretreatment compared to untreated plasma controls. No significant differences in LDL/VLDL plasma cholesterol:triglyceride concentration ratio following 18 h of DTNB pretreatment was observed. An increased number of discoidal HDL particles were observed following 18 h of DTNB pretreatment. When Ann. was incubated in plasma pretreated with DTNB for 18 h the percentage of Ann. recovered in the HDL, LDL, and VLDL fractions significantly increased. However, the percentage of Ann. recovered within the LPDP fraction was significantly decreased. When LAnn was incubated in plasma pretreated with DTNB for 18 h the percentage of Ann. recovered in the HDL fraction significantly decreased. The percentage of Ann. recovered in the LPDP fraction significantly increased when LAnn was incubated in plasma pretreated with DTNB for 18 h. No significant differences in Ann. lipoprotein distribution were observed when Ann. and LAnn were co-incubated with DTNB in plasma for 1 h. These findings suggest that the cholesterol:triglyceride concentration ratio and physical structure of HDL maybe important in defining the capacity of HDL to sequester Ann.     

Potencies of lipoproteins in fasting and postprandial plasma to accept additional cholesterol molecules released from cell membranes

To investigate the role of various lipoproteins in plasma to promote cholesterol efflux from cell membranes, potencies of lipoproteins in normolipidemic fasting and postprandial (PP) plasmas to accept additional cholesterol molecules from cell membranes were determined. We used red blood cells (RBCs) and lipoproteins in fresh blood as donors and acceptors of cell membrane cholesterol, respectively. When fresh fasting plasma (n=24) containing active lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer proteins (CETP) was incubated with a 3-fold excess of autologous RBCs at 37 degrees C for 18 hours, plasma cholesterol levels increased by 19.6% (38.5+/-14.2 mg/dL) owing to an exclusive increase in the CE level. Very low density lipoprotein (VLDL), low density lipoprotein (LDL), and high density lipoprotein (HDL) fractions retained 48.1%, 26.3%, and 25.6% of the net cholesterol mass increase in fasting plasma, resulting in 91%, 8%, and 21% increases in their cholesterol contents, respectively. The PP plasma was 1.3-fold more potent than fasting plasma in promoting cholesterol efflux from RBCs by associating excess cholesterol with chylomicrons, resulting in a 356% increase in the cholesterol content of chylomicrons. These increases in lipoprotein cholesterol content indicate that chylomicrons were about 3.9x, 44x, and 17x more potent than fasting VLDL, LDL, and HDL, respectively, in accepting additional cholesterol molecules released from RBCs. The capacity of PP plasma to promote cholesterol efflux from RBCs was significantly correlated with plasma cholesterol levels (r=0.60, P<0.005), triglycerides (r=0.68, P<0.001), chylomicrons (r=0.90, P<0.001), VLDL (r=0.65, P<0.001), and LDL (r=0.47, P<0.025) but not with the levels of HDL (r= -0.34, P<0.20). In fasting plasma containing a low level of VLDL and HDL, isolated chylomicrons supplemented to the plasma were approximately 9x more potent than HDL in boosting the capacity of plasma to promote cholesterol efflux from RBCs. This study indicates that chylomicrons in PP plasma are the most potent ultimate acceptors of cholesterol released from cell membranes and that a low HDL level is not a factor that limits the ability of PP plasma to promote cholesterol efflux from cell membranes. Our data obtained from an in-vitro system suggest that PP chylomicrons may play a major role in promoting reverse cholesterol transport in vivo, since the transfer of cholesterol from cell membranes to chylomicrons will lead to the rapid removal of this cholesterol by the liver. HDL in vivo may promote reverse cholesterol transport by enhancing the rapid removal of chylomicrons from the circulation, since the rate of clearance of chylomicrons is positively correlated with the HDL level in plasma.     

The insulin resistance syndrome in native Hawaiians. Native Hawaiian Health Research (NHHR) Project

OBJECTIVE: To investigate whether fasting hyperinsulinemia is associated with a clustering of cardiovascular disease (CVD) risk factors, manifesting as the insulin resistance syndrome (IRS), in a population of native Hawaiians. RESEARCH DESIGN AND METHODS: A total of 574 native Hawaiians > or = 30 years of age were examined for blood pressure, waist-to-hip ratio (WHR), BMI, oral glucose tolerance, and fasting lipid, insulin, and C-peptide concentrations. All statistical analyses (n = 384) excluded 190 individuals who had NIDDM or who were taking hypertension medication. Using logistic regression analysis, fasting insulin and C-peptide levels were compared with CVD risk factors (glucose intolerance, hypertension, central adiposity, elevated triglyceride levels, and low HDL cholesterol levels) after adjusting for age and obesity. RESULTS: Sixty-six percent of native Hawaiians were overweight or obese, and 70% were found to have central adiposity. Fasting insulin concentrations were correlated with BMI, WHR, blood pressure, and triglyceride, HDL cholesterol, and glucose concentrations. Fasting insulin was also significantly associated with an increasing number of CVD risk factors in each participant (P < 0.001). Fasting insulin and C-peptide concentrations were independently associated with glucose intolerance, high triglyceride levels, and low HDL cholesterol levels. However, only fasting C-peptide concentrations were independently associated with hypertension and central adiposity. Apparent differences in the correlates of fasting insulin and C-peptide may be related to multiple factors and warrant further evaluation. CONCLUSIONS: This study provides cross-sectional data confirming the existence of the IRS in native Hawaiians. However, further longitudinal studies are needed to examine the relationship of insulin resistance and/or surrogate markers to increased rates of NIDDM and CVD mortality in native Hawaiians.     

LDL particle size and LDL and HDL cholesterol changes with dietary fat and cholesterol in healthy subjects

We have conducted a dietary trial in 54 men and 51 women with a wide range of fasting cholesterol values to examine the use of low density lipoprotein (LDL) particle size to predict the lipoprotein response to dietary fat and cholesterol. After a 2-week low fat period, subjects were given two liquid supplements in addition to their low fat diet for 3 weeks each, one containing 31-40 g of fat and 650-845 mg of cholesterol, the other fat free. LDL particle type was determined by 3-15% gradient gel electrophoresis. On multiple regression, LDL type was independently related to plasma triglyceride (P < 0.001), waist circumference (P < 0.01), and high density lipoprotein (HDL) (P < 0.001) accounting for 56% of the variance in LDL type in the whole group. Change in LDL cholesterol with dietary fat and cholesterol was unrelated to LDL particle size in either men or women. However, change in HDL cholesterol in men was strongly related to LDL particle type (r = -0.52, P = 0.001) and change in HDL2 cholesterol in women was related to LDL particle type (r = -0.40, P < 0.01). In conclusion, we are unable to confirm the finding that LDL particle type can predict changes in LDL cholesterol following changes in dietary fat intake. However, LDL particle type can independently predict changes in HDL cholesterol in men and accounts for 27% of the variance.