Postprandial elevation of ApoB-48-containing triglyceride-rich particles and retinyl esters in normolipemic males who smoke

Smokers have an increased risk for coronary artery disease (CAD), which can only partly be explained by fasting lipoprotein changes. Recent studies have indicated that smokers express metabolic abnormalities characteristic of insulin resistance syndrome. A preliminary study reported an increased postprandial triglyceride (TG) response in smokers compared with nonsmokers. To investigate the effect of smoking on postprandial lipemia, a fat-rich mixed meal (837 kcal, 63 g of fat) was served to 12 healthy smokers and 12 controls with similar fasting lipoprotein profiles, body composition, and lifestyles. Blood was drawn before and 3, 4, 6, and 8 hours postprandially, and triglyceride-rich lipoprotein (TRL) fractions (chylomicrons, VLDL1, VLDL2, and IDL) were separated with density gradient ultracentrifugation. Pre- and postprandial TG, retinyl esters (RE), apolipoprotein B-48 (apoB-48) and B-100 (apoB-100) were measured in each fraction. Smokers showed a significantly increased postprandial TG response in chylomicrons, VLDL1, and VLDL2. The areas under the incremental curve (AUIC) of apoB-48 in chylomicrons (2.83 +/- 0.84 versus 0.56 +/- 0.17; P < .05) and VLDL1 (10.17 +/- 1.96 versus 2.95 +/- 2.44; P = < .01) were markedly higher in smokers than in controls. Changes of RE responses of all TRL fractions were consistent with those of apoB-48. Postprandial apoB-100 concentrations and lipolytic enzymes were similar between the two groups. In conclusion, smokers have the syndrome of impaired TG tolerance because of defective clearance of chylomicrons and their remnants. Prolonged residence time of atherogenic remnant particles may constitute a significant risk factor for CAD in smokers.     

Decreased postprandial high density lipoprotein cholesterol and apolipoproteins A-I and E in normolipidemic smoking men: relations with lipid transfer proteins and LCAT activities

We have previously reported that normolipidemic smokers are lipid intolerant due to increased responses of triglyceride-rich lipoproteins (TRL) apolipoprotein B-48, triglyceride (TG), and retinyl esters to a mixed meal compared to non-smokers. To investigate whether postprandial high density lipoprotein (HDL), apolipoprotein A-I (apoA-I), apolipoprotein A-II (apoA-II), and apolipoprotein E (apoE) concentrations or lipid transfer protein activities are affected by cigarette smoking, we investigated 12 male smokers and 12 non-smokers with comparable fasting lipoprotein profile, BMI, and age. Plasma samples obtained after an overnight fast and postprandially were separated by density gradient ultracentrifugation. Postprandial apoA-I, lipoprotein AI-particles (LpA-I), HDL-cholesterol, and HDL apoE concentrations decreased in smokers, but remained unchanged in controls. Concomitantly, cholesterol and apoE concentrations increased significantly in TRL fractions in smokers. Fasting lecithin:cholesterol acyltransferase (LCAT) and phospholipid transfer protein (PLTP) activity levels, as well as esterification rates (EST) and phospholipid transfer rates were comparable between the groups. Cholesteryl ester transfer protein (CETP) activity levels were lower in the smokers. Postprandially EST increased, but CETP and PLTP activities deceased in smokers as compared to controls. We conclude, that even healthy, normolipidemic smokers have altered postprandial high density lipoprotein (HDL) cholesterol and apolipoprotein composition, as well as lipid transfer protein activities. The shift of cholesterol and apoE from HDL to the triglyceride-rich lipoprotein (TRL) fraction, together with decreased plasma apoA-I and LpA-I concentrations during alimentary lipemia may indicate impaired reverse cholesterol transport. Both the postprandial increase in TRL and the lowering of HDL may promote atherogenesis in smokers.     

Sagittal abdominal diameter as a practical predictor of visceral fat

OBJECTIVE: To evaluate the relationships between the supine sagittal abdominal diameter (SAD) and visceral fat, as well as to evaluate intra- and inter-observer reliability of sagittal diameter measurement. PATIENTS: Twenty-eight women ranging in age from 27-78 y with a body mass index (BMI) ranging from 16.9-48.1 kg/m2 and 23 men ranging in age from 32-75 y with BMI ranging from 20-41.6 kg/m2. MEASUREMENT: Body fat distribution was measured by waist circumference, waist to hip ratio (WHR), SAD, anthropometrically assessed and a single slice of computed tomography (CT) at the L4-L5 level. RESULTS: In both genders, a significant association was found between visceral adipose tissue (AT) and SAD, as evaluated by CT (women r = 0.80; men r = 0.83, P < 0.001), and SAD by anthropometry (women r = 0.76; men r = 0.82, P < 0.001), as well as between visceral AT and waist circumference (women r = 0.76, men r = 0.86, P < 0.001) and WHR (women r = 0.57, P < 0.01, men r = 0.80, P < 0.001). A significant association was also found between subcutaneous AT and SAD by anthropometry (women r = 0.79, men r = 0.74, P < 0.001). After adjusting for BMI, the association between subcutaneous AT and SAD was no longer significant in men and only moderately significant in women (r = 0.42, P < 0.05), while the association between visceral AT and SAD by anthropometry remained significant in both genders (women r = 0.63, P < 0.001; men r = 0.66, P < 0.001). When the subjects were divided into two groups according to BMI (lean to moderately overweight women with BMI < 28 and men with BMI < 30 and obese women with BMI > 28 and men with BMI > 30) we found that the relationships between SAD by anthropometry, as well as SAD by CT and visceral AT, were higher in lean to moderately overweight subjects than in those who were obese. High inter-observer correlation was found concerning SAD measurement (r = 0.99, P < 0.001). Intra- and inter-observer precision as evaluated by coefficient of variation and intraclass correlation coefficient for SAD measurement was very high. CONCLUSION: Our study shows the usefulness of SAD by anthropometry to predict visceral fat and its very high inter- and intra-observer precision.     

Zinc and flunitrazepam modulation of GABA-mediated currents in rat suprachiasmatic neurons

We know that upper body obesity is associated with metabolic complications, but we don't know how regional body fat distribution influences postprandial lipemia in obese adults. Thus, this study explored the respective effects of android or gynoid types of obesity and fasting triglyceridemia on postprandial lipid metabolism and especially triglyceride-rich lipoproteins. Twenty-four obese and 6 lean normotriglyceridemic women (control), age 24-57 yr, were enrolled. Among obese women with an android phenotype, 9 exhibited normal plasma triglyceride levels (mean: 1.38 mmol/L) (NTAO), and 7 displayed a frank hypertriglyceridemia (mean: 2.40 mmol/L) (HTAO). The 8 patients with a gynoid phenotype had normal triglyceride levels (mean: 1.00 mmol/L) (GO). All were given a mixed test meal providing 40 g triglycerides. Serum and incremental chylomicron triglycerides 0-7 h areas under the curve (AUCs) as well as triglyceride levels in apoB-48-containing triglyceride-rich lipoprotein (TRLs) or chylomicrons were significantly higher in HTAOs and NTAOs than in GOs and controls postprandially. The size of chylomicron particles was bigger in controls and GOs than in HTAOs and NTAOs postprandially. Android obese subjects showed abnormally elevated fasting apoB-48 and apoB-100 triglyceride-rich lipoprotein (TRL) levels. Most abnormalities that were found correlated to plasma levels of insulin and apoC-III. In conclusion, an abnormal postprandial lipid pattern is a trait of abdominal obesity even without fasting hypertriglyceridemia.     

Liquid chromatographic method for analysis of all-rac-alpha-tocopheryl acetate and retinyl palmitate in milk-based infant formula using matrix solid-phase dispersion

We compared the fasting and postprandial response to a National Cholesterol Education Program (NCEP) II diet with that of a diet high in total (40% of energy) and saturated fat. In free-living conditions, 17 healthy normolipidemic, normoglycemic men and women consumed a high-fat diet, a maintenance diet and the NCEP II diet, for 1 mo each. At the completion of each dietary period, an oral fat load (70 g/m2 body surface area) was administered and plasma triacylglycerol (TAG) determined every 2 h for 8 h. Compared with the high-fat phase, the NCEP II diet was associated with significantly lower energy intake (12.1 +/- 1.1 vs. 7 +/- 0.7 MJ/d) and final body weight (78 +/- 3.8 vs. 76.3 +/- 3.5 kg) (P < 0.01). Plasma high density lipoprotein cholesterol, apolipoprotein (apo) A-I and ApoB concentrations were also significantly lower when subjects consumed the NCEP II diet rather than the high-fat diet (P 相似文献   

Postprandial lipoprotein responses in hypertriglyceridemic subjects with and without cardiovascular disease

Three groups of age- and weight-matched men (aged 40 to 70 years) without diabetes were studied: controls (n = 10), plasma triglycerides (TG) less than 180 mg/dL and no cardiovascular disease (CVD); HTG-CVD (n = 11), hypertriglyceridemic (HTG) (TG > 240 mg/dL) without CVD; and HTG+CVD (n = 10), HTG (TG > 240 mg/dL) with documented CVD. HTG+CVD subjects had higher fasting and post-oral glucose tolerance test insulin levels than the other two groups, respectively. Very-low-density lipoprotein (VLDL)+chylomicrons (CMs), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL), and three high-density lipoprotein (HDL) subfractions (HDL-L, HDL-M, and HDL-D, from least to most dense) were isolated by gradient ultracentrifugation. Fasting lipoproteins were similar in HTG groups, except for higher VLDL lipid to apolipoprotein (apo) B ratios (P < .04) in the HTG+CVD group. Subjects were fed a high-fat mixed meal, and lipoprotein composition was determined at 3, 6, 9, and 12 hours postprandially. Postprandial responses of the core lipids (TG and cholesterol esters [CE]) in all of the lipoprotein subfractions were similar in the two HTG groups at each time point. However, both controls and HTG-CVD subjects had increases in HDL-M phospholipid (PL) at 9 and 12 hours with no change in HDL-D PL. The HTG+CVD group, on the other hand, had no increase in HDL-M PL and had a substantial reduction in HDL-D PL. These changes resulted in significant increases in HDL-M and HDL-D PL to apo A-I ratios in both controls and HTG-CVD subjects between 6 and 12 hours, whereas there was no increase seen in the HTG+CVD group. The HTG-CVD group also had a significantly greater increase in the VLDL+CM PL to apo B ratio (P = .038) at 3 hours than the HTG+CVD group. This diminished amount of surface lipid per VLDL particle may account for the late decrease in the HDL-D PL to apo A-I ratio seen in HTG+CVD patients. There were no other postprandial lipid or apolipoprotein differences between the two HTG groups. We conclude therefore that the major postprandial lipoprotein abnormality in these HTG+CVD patients was a failure to increase the PL content per particle in VLDL+CM, HDL-M, and HDL-D. This abnormality could prevent the usual increase in reverse cholesterol transport seen in postprandial plasma and therefore contribute to their increased incidence of CVD. The greater insulin resistance seen in these patients also appears to contribute significantly to their CVD.     

Evidence that plasma leptin and insulin levels are associated with body adiposity via different mechanisms

OBJECTIVE: Like insulin, the adipocyte hormone, leptin, circulates at levels proportionate to body adiposity. Because insulin may regulate leptin secretion, we sought to determine if plasma leptin levels are coupled to body adiposity via changes in circulating insulin levels or insulin sensitivity and whether leptin secretion from adipocytes is impaired in subjects with NIDDM. RESEARCH DESIGN AND METHODS: We used multiple linear regression to analyze relationships between BMI (a measure of body adiposity) and fasting plasma levels of leptin and insulin in 98 nondiabetic human subjects (68 men/30 women) and 38 subjects with NIDDM (27 men/11 women). The insulin sensitivity index (Si) was also determined in a subset of nondiabetic subjects (n = 38). RESULTS: Fasting plasma leptin concentrations were correlated to both BMI (r = 0.66, P = 0.0001) and fasting plasma insulin levels (r = 0.65, P = 0.0001) in nondiabetic men and women (r = 0.58, P = 0.0009 for BMI; r = 0.47, P = 0.01 for insulin). While the plasma leptin level was also inversely related to Si (r = -0.35; P = 0.03), this association was dependent on BMI, whereas the association between insulin and Si was not. Conversely, the relationship between plasma leptin and BMI was independent of Si, whereas that between insulin and BMI was dependent on Si. The relationship between plasma leptin levels and BMI did not differ significantly among NIDDM subjects from that observed in nondiabetic subjects. CONCLUSIONS: We conclude that 1) body adiposity, sex, and the fasting insulin level are independently associated with plasma leptin level; 2) because NIDDM does not influence leptin levels, obesity associated with NIDDM is unlikely to result from impaired leptin secretion; and 3) insulin sensitivity contributes to the association between body adiposity and plasma levels of insulin, but not leptin. The mechanisms underlying the association between body adiposity and circulating levels of these two hormones, therefore, appear to be different.     

Cholecystokinin and pancreatic polypeptide release in diabetic patients with and without autonomic neuropathy

The present study was undertaken to investigate postprandial responses of cholecystokinin (CCK) and pancreatic polypeptide (PP) and their interrelationship in patients with diabetes mellitus (DM) with and without autonomic neuropathy (AN). Twenty-two patients with DM (seven with AN and 15 without AN) and 14 age-matched healthy controls were studied. AN was diagnosed according to several tests of cardiovascular autonomic function. CCK and PP plasma levels were measured by specific radioimmunoassays before and at several time points after the oral administration of a test meal. Basal CCK plasma levels in DM patients were normal, whereas basal PP plasma levels were increased (139 +/- 18 vs 72 +/- 7 pg/ml; P < 0.01). Integrated postprandial CCK response was increased in DM patients (208 +/- 27 vs 110 +/- 14 pmol/liter/2 hr; P < 0.05), mainly due to the patients with AN. Postprandial PP response was increased in DM patients without AN (37,273 +/- 5241 vs 13,418 +/- 3299 pg/ml/2 hr; P < 0.001) but not in those with AN (8887 +/- 3461 pg/ml/2 hr). Moreover, PP response was closely (P < 0.002) correlated with the degree of AN. A direct and linear correlation between postprandial CCK and PP responses was found in healthy controls (r = 0.78; P < 0.005) but not in DM patients. We conclude that the CCK response to a meal is increased in diabetic patients with AN, whereas the PP response is increased only with an intact autonomic nervous system.(ABSTRACT TRUNCATED AT 250 WORDS)     

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)     

Effect of fluoxetine on the plasma concentrations of clozapine and its major metabolites in patients with schizophrenia

Triglyceride levels and free fatty acid metabolism are influenced by body fat distribution. To test whether the pattern of fat distribution in obese subjects results in distinct insulin mediated suppression of non-esterified fatty acids which could account for differences in plasma triglycerides, we studied 59 obese subjects who were classified according to waist-to-hip ratio. Non-esterified fatty acids and insulin response to a 75 g oral glucose tolerance test were higher in abdominal obesity. Total non-esterified fatty acids response, after adjustment for sex, showed a positive association with waist-to hip ratio (r = 0.292; p < 0.05). The abdominal obese group had higher fasting triglycerides (1.74+/-0.83 versus 1.11+/-0.71 mmol/L; p = 0.003) and lower glucose/insulin ratio (5.2+/-2.3 versus 7.1+/-2.4; p = 0.003). Stepwise multiple regression analysis showed that triglyceride levels are explained by fasting and 120 min non-esterified fatty acids and by glucose/insulin ratio. We conclude that abdominal obesity is associated with a higher resistance to insulin mediated suppression of non-esterified fatty acids in obese subjects. Variation of triglyceride concentrations in obesity is dependent on both fasting and 120 min non-esterified fatty acids as well as on insulin sensitivity to glucose utilization.     

Evidence for an inhibitory effect of physiological levels of insulin on the growth hormone (GH) response to GH-releasing hormone in healthy subjects

It has been previously reported that in healthy subjects, the acute reduction of free fatty acids (FFA) levels by acipimox enhances the GH response to GHRH. In the present study, the GH response to GHRH was evaluated during acute blockade of lipolysis obtained either by acipimox or by insulin at different infusion rates. Six healthy subjects (four men and two women, 25.8 +/- 1.9 yrs old, mean +/- SE) underwent three GHRH tests (50 micrograms iv, at 1300 h) during: 1) iv 0.9% NaCl infusion (1200-1500 h) after oral acipimox administration (250 mg) at 0700 h and at 1100 h; 2) 0.1 mU.kg-1.min-1 euglycemic insulin clamp (1200-1500 h) after oral acipimox administration (250 mg at 0700 h and at 1100 h); 3) 0.4 mU.kg-1.min-1 euglycemic insulin clamp (1200-1500 h) after oral placebo administration (at 0700 and 1100 h). Serum insulin (immunoreactive insulin) levels were significantly different in the three tests (12 +/- 2, 100 +/- 10, 194 +/- 19 pmol/L, P < 0.06), plasma FFA were low and similar (0.04 +/- 0.003, 0.02 +/- 0.005, 0.02 +/- 0.003, not significant), and the GH response to GHRH was progressively lower (4871 +/- 1286, 2414 +/- 626, 1076 +/- 207 micrograms/L 120 min), although only test 3 was significantly different from test 1 (P < 0.05). Pooling the three tests together, a significant negative regression was observed between mean serum immunoreactive insulin levels and the GH response to GHRH (r = -0.629, P < 0.01). Our results indicate that in healthy subjects, acipimox and hyperinsulinemia produce a similar decrease in FFA levels and that at similar low FFA, the GH response to GHRH is lower during insulin infusion than after acipimox. These data suggest that insulin exerts a negative effect on GH release. Because the insulin levels able to reduce the GH response to GHRH are commonly observed during the day, for instance during the postprandial period, we conclude that the insulin negative effect on GH release may have physiological relevance.     

Visceral fat accumulation is an important determinant of PAI-1 levels in young, nonobese men and women: modulation by cross-sex hormone administration

Increased plasminogen activator inhibitor type-1 (PAI-1) levels, leading to impaired fibrinolysis, are associated with increased visceral fat in middle-aged and obese subjects. It is unknown, however, whether this association is independent of other disturbances clustered in the insulin resistance syndrome. We analyzed this association in young, nonobese transsexual men and women before and after administration of cross-sex steroids, which potentially influence many elements of the insulin resistance syndrome, including PAI-1 levels and visceral fat accumulation. We assessed the visceral fat area (by MRI); total body fat; insulin sensitivity (with a glucose clamp technique); and plasma levels of PAI-1, insulin, and triglycerides in young (<37 years old), nonobese (body mass index <28 kg/m2), healthy men (n=18) and women (n=15) before and after 12 months of cross-sex hormone administration. Men were treated with ethinyl estradiol 100 microgram/d plus cyproterone acetate 100 mg/d, and women were treated with testosterone esters 250 mg IM every 2 weeks. At baseline, only visceral fat area was significantly correlated with plasma PAI-1 levels in both men (r=0.57, P=0.03) and women (r=0.59, P=0.03). In multivariate linear regression analysis, this association was independent of total body fat, insulin sensitivity, and plasma levels of triglycerides and insulin. After 12 months of cross-sex hormone administration, the plasma PAI-1 levels were no longer correlated with visceral fat (which had increased). We conclude that in young, nonobese men and women, visceral fat area is an important determinant of plasma PAI-1 levels. After cross-sex hormone administration, this association was no longer demonstrable.     

Renin-angiotensin system: involvement in polycystic ovarian syndrome

OBJECTIVE: To investigate the relationship between renin-angiotensin system (RAS) and polycystic ovarian syndrome (PCOS) METHODS: A pituitary-stimulating test with luteinizing hormone releasing hormone (LRH, 100 micrograms) was performed in two PCOS groups with similar mean testosteron (T) levels of luteinizing hormone/follicular stimulating hormone (LH/FSH) (LH/FSH > or = 3, group 1, n = 15; LH/FSH < 3, group 2, n = 15) and the controls (n = 20) of matched body mass index with group 1. The basal level and LRH-evoked responses of LH, plasma renin activity (PRA), angiotensin II (AT II ) and aldosterone (ALD) were measured by RIA with commercially available kits. In the basal state, a positive correlation was found between T and AT II levels (r = 0. 49, P < 0.05) in all PCOS subjects. After LRH administration, susceptible individuals, especially of group 1 had exaggerated responses of LH, PRA, AT II and ALD as compared with the controls, and a positive correlation was also found between peak levels of LH and AT II (r = 0.54, P < 0.01). CONCLUSIONS: There is enhanced RAS function in PCOS especially in group 1. This may contribute to the excess androgen production and high incidence of ovarian hyperstimulation syndrome in this disorder.     

Association of halofantrine with postprandially derived plasma lipoproteins decreases its clearance relative to administration in the fasted state

The oral bioavailability of halofantrine (Hf), a highly lipophilic phenanthrenemethanol antimalarial, is significantly enhanced when ingested with food. Although food enhances the absorption of Hf, it also alters the intrinsic pharmacokinetics of Hf as the observed postprandial absolute bioavailability was greater than 100% (Humberstone et al., J. Pharm. Sci. 1996, 85, 525-529). In this study, the association of Hf with plasma lipoproteins and the effect of postprandial lipoproteins on the pharmacokinetics of Hf after intravenous administration was examined in beagles. In fasted dogs, approximately 50% of plasma Hf was associated with lipoproteins, with HDL accounting for 42-43%, LDL for 4-5%, and triglyceride rich lipoproteins (TRL) for 2-3%. At 0.5 and 2 h postdosing in the postprandial state, the proportion of Hf present in both TRL and LDL increased to 7-10%. Changes in Hf distribution between lipoprotein fractions reflected the respective postprandial changes in plasma triglyceride (TG) concentrations. In terms of pharmacokinetics, when an equivalent dose of Hf was administered intravenously in a crossover study to fed and fasted beagles, plasma Hf AUC values were significantly higher, and CL and Vss were significantly lower, in the fed state compared to the fasted state (p < 0.05). The mean postprandial increase in plasma AUC values was 19% (range 14-34%), with corresponding decreases in CL (15%) and Vss (21%). A broadly linear relationship between increased postprandial Hf concentrations at specific time points (fed vs fasted) and corresponding postprandial increases in TG concentrations suggested that the decreased postprandial clearance of Hf was a function of increased association with TG-rich plasma lipoproteins. This study confirms that the clearance of Hf is influenced by plasma lipoprotein profiles, and the findings have implications for the design and interpretation of fed/fasted bioavailability studies of lipophilic drugs and determination of their intrinsic pharmacokinetic parameters in subjects or patients with dyslipidemic profiles.     

Alanine germination receptors of Bacillus subtilis

OBJECTIVES: To evaluate total visceral adipose tissue (AT) volumes in relation to single slices of visceral AT area measured at different levels and to other simple anthropometric measurements. DESIGN: Only outpatients examined in a metabolic unit were considered; subjects without conditions known to affect AT distribution who gave their informed consent were recruited. SETTING: All subjects were hospitalized in the Department of Internal Medicine of the University of Messina. SUBJECTS: 90 adult subjects of which 18 men and 42 pre- and 30 post-menopausal women. Ages ranged from 18 to 69 years and body mass indexes ranged from 22 to 50. INTERVENTIONS: The AT volume was calculated by computed tomography from the AT area of five scans and from the distances between these scans. RESULTS: AT area at the level of the 2nd-3rd lumbar vertebra had by itself the highest predictive power in men (s.e. = 6.8%), in post-menopausal women (s.e. = 7.4%) and, together with age, in pre-menopausal women (s.e. = 14%). Of the non-radiological parameters it was waist circumference, together with age, which showed the highest predictive power in men (s.e. = 21%), pre-menopausal women (s.e. = 25%) and, together with height, in post-menopausal women (s.e. = 33%). CONCLUSIONS: A single scan measurement at the lumbar level was confirmed to be representative of total visceral AT volume. Waist circumference was the non-radiological parameter that best correlated with volume.     

Gastric emptying in Mexican Americans compared to non-Hispanic whites

Mexican Americans, a group at high risk for type II diabetes mellitus, have higher postprandial insulin and glucose levels when compared to non-Hispanic whites. A rapid rate of gastric emptying contributes to an increased rate of nutrient absorption and subsequent greater elevation of postprandial glucose and insulin levels. A more rapid rate of gastric emptying and hyperinsulinemia have been observed in patients with recently diagnosed type II diabetes mellitus. In this study, we examined whether Mexican Americans have a more rapid rate of gastric emptying than non-Hispanic whites. Gastric emptying studies were performed on 32 nondiabetic Mexican Americans and on 31 nondiabetic non-Hispanic whites. The rate of gastric emptying following a liquid glucose meal was measured. Serum insulin, plasma glucose, and GIP levels were measured in fasting and postprandial blood samples collected at 15-min intervals for 2 hr. Adjusting for age, body mass index, and gender, the gastric half-emptying time of a glucose meal was significantly (P < 0.05) more rapid for the Mexican American subjects (56.5 +/- 3.4 min) compared to the non-Hispanic white subjects (66.4 +/- 3.5 min). Nondiabetic Mexican Americans empty a liquid glucose meal more rapidly from their stomachs than nondiabetic non-Hispanic whites. Rapid gastric emptying is associated with hyperinsulinemia as a normal physiologic response to increased nutrient availability. The rapid gastric emptying observed in nondiabetic Mexican Americans is associated with hyperinsulinemia and could be a contributing factor for the increased risk of obesity and type II diabetes in this population.     

Fasting hyperinsulinemia and cardiovascular disease risk factors in nondiabetic adults: stronger associations in lean versus obese subjects. Atherosclerosis Risk in Communities Study Investigators

The association between hyperinsulinemia and atherogenic risk factors has not been well studied in blacks and may be different for obese versus lean individuals. To investigate this possibility and to confirm the associations of hyperinsulinemia with cardiovascular disease risk factors in blacks and whites, we analyzed the joint associations of fasting serum insulin and obesity with risk factors in the Atherosclerosis Risk in Communities (ARIC) Study (1,293 black men, 4,797 white men, 2,033 black women, and 5,445 white women). Insulin values > or = 90th percentile (> or = 21 microU/mL) constituted hyperinsulinemia; body mass index (BMI) values > or = 27.3 kg/m2 for women and > or = 27.8 for men constituted obesity. Participants with hyperinsulinemia in all four race-sex groups had more atherogenic levels of most risk factors studied than those with normoinsulinemia. Among black men and women, mean levels of triglycerides, low-density lipoprotein cholesterol (LDL-C), apolipoprotein (apo) B, glucose, and fibrinogen (men only) were higher in hyperinsulinemic lean participants as compared with the normoinsulinemic obese group. Furthermore, most associations between insulin level and risk factors were stronger among lean versus obese subjects. For example, among lean black men, the difference in mean triglyceride concentration between those with hyperinsulinemia and those with normoinsulinemia was 147 - 99 = 48 mg/dL; among obese black men, the difference was 155 - 121 = 34 mg/dL (P < .05 for the interaction). Generally, similar negative interactions between BMI and insulin concentration were also observed among whites.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of visceral fat accumulation on uric acid metabolism in male obese subjects: visceral fat obesity is linked more closely to overproduction of uric acid than subcutaneous fat obesity

We investigated the relationship between uric acid (UA) metabolism and fat distribution in 36 obese men with a mean +/- SD age of 38 +/- 16 years and mean body-mass index (BMI) of 34 +/- 4 kg/m2. Subjects were divided into two groups: subcutaneous fat obesity (SFO) and visceral fat obesity (VFO), according to their abdominal fat distribution based on the results of computed tomography (CT). SFO was defined as having a ratio of visceral fat area (VFA) to subcutaneous fat area (V/S) of less than 0.4, and VFO was defined as having a V/S ratio > or = 0.4. The levels of serum total cholesterol (T-Chol), triglyceride (TG), and fasting plasma glucose (FPG), and the diastolic blood pressure (dBP) were significantly higher in the VFO group than in the SFO group. Serum UA levels were much higher in both the SFO and VFO groups than in the non-obese control group (492 +/- 107 and 474 +/- 90 v 309 +/- 48 micromol/L, respectively). The 24-hour urinary urate excretion (u-UA24h) and the UA clearance (Cua) to creatinine clearance (Ccr) ratio were significantly higher in the VFO group than in the SFO group (3.75 +/- 1.43 v 2.69 +/- 1.12 mmol/d, P < .05; and 5.9% +/- 2.0% v 3.6% +/- 1.7%, P < .001, respectively). The frequency of hyperuricemia was markedly higher in both the SFO and VFO groups compared with the control group (71% and 73% v 0%, respectively). Although the high serum UA level seemed to be related to low u-UA24h in 80% of SFO subjects with hyperuricemia, this was the case in only 10% of VFO subjects. While 44% of VFO subjects with hyperuricemia were designated as an overproduction type. These results suggest that the mechanism of hyperuricemia in obesity may be affected by the difference in body fat distribution and that the assessment of body fat distribution and types of hyperuricemia is crucial for the treatment of obese patients with hyperuricemia.     

Lower androgenicity is associated with higher plasma levels of prothrombotic factors irrespective of age, obesity, body fat distribution, and related metabolic parameters in men

The purpose of this study was to examine the relationships between androgenic status and plasma levels of both prothrombotic and antithrombotic factors in men, irrespective of obesity, body fat distribution, and metabolic parameters. Sixty-four apparently healthy men, 40 with a body mass index (BMI) greater than 25 kg/m2 (overweight and obese [OO]) and 24 non-obese controls with a BMI less than 25, were selected and evaluated for (1) plasma concentrations of plasminogen activator inhibitor-1 (PAI-1) antigen, PAI-1 activity, fibrinogen, von Willebrand factor (vWF) antigen, vWF activity, and factor VII (FVII) as the prothrombotic factors; (2) plasma levels of tissue plasminogen activator (TPA) antigen, protein C, and antithrombin III as the antithrombotic factors; (3) fasting plasma concentrations of insulin and glucose and the lipid pattern (triglycerides [TG] and total and high-density lipoprotein [HDL] cholesterol) as the metabolic parameters; and (4) free testosterone (FT), dehydroepiandrosterone sulfate (DHEAS), and sex hormone-binding globulin (SHBG) serum levels as the parameters of androgenicity. Body fat distribution was evaluated by the waist to hip ratio (WHR). In OO and non-obese subjects taken together, plasma levels of PAI-1 antigen, fibrinogen, and FVII were inversely associated with FT (r = .255, P < .05, r = -3.14, P < .05, and r = -.278, P < .05, respectively), and the negative relationships of both fibrinogen and FVII with FT were maintained after stepwise multiple regression analysis. Plasma concentrations of PAI-1 antigen and PAI-1 activity were also negatively correlated with SHBG (r = -.315, P < .05 and r = -.362, P < .01, respectively), and these associations held irrespective of the other parameters investigated. None of the antithrombotic and fibrinolytic factors were independently related to serum androgen levels. Subjects with a BMI higher than 25 kg/m2 had higher plasma concentrations of PAI-1 antigen, PAI-1 activity, and fibrinogen as compared with non-obese controls (P < .001, P < .001, and P < .01, respectively). In addition, in OO and control subjects as a whole, multiple stepwise regression analysis showed that the associations of BMI with PAI-1 activity, fibrinogen, vWF antigen, and vWF activity were independent of any other metabolic and hormonal parameters. Plasma concentrations of PAI-1 antigen, PAI-1 activity, and fibrinogen were also directly correlated with WHR in all subjects taken together, irrespective of the other parameters investigated. Evaluation of antithrombotic factors showed that OO subjects had higher TPA plasma concentrations than non-obese controls (P < .001), whereas protein C and antithrombin III did not differ in the two groups. TPA was also directly correlated with BMI (r = .415, P < .001) and WHR (r = .393, P < .001) in all subjects. The results of this study indicate that (1) men with lower FT serum levels have higher fibrinogen and FVII plasma concentrations, and those with lower SHBG serum levels also have higher levels of PAI-1 antigen and activity; (2) irrespective of other factors, obesity per se may account for higher concentrations of PAI-1, fibrinogen, and vWF; (3) plasma levels of PAI-1 (antigen and activity) and fibrinogen correlate independently with WHR; and (4) among the investigated antithrombotic factors (TPA antigen, protein C, antithrombin III), only TPA antigen plasma concentrations are higher in men with abdominal obesity. Thus, because of the increase in several prothrombotic factors, men with central obesity, particularly those with lower androgenicity, seem to be at greater risk for coronary heart disease (CHD). Apparently, this risk is not counteracted by a parallel increase in plasma concentrations of antithrombotic factors.     

Association of fasting plasma free fatty acid concentration and frequency of ventricular premature complexes in nonischemic non-insulin-dependent diabetic patients

We investigated the association between free fatty acid (FFA) concentration and ventricular premature complexes (VPCs) in nonischemic patients with non-insulin-dependent diabetes mellitus using 3 approaches: cross-sectional analysis (n = 142), intervention including induction of elevated FFA levels with Intralipid heparin (n = 15), and reduction in FFA levels with Acipimox (n = 34) and a longitudinal follow-up study (n = 59). Patients at the third tertile of fasting plasma FFA concentration had the strongest increase in VPCs. Independently of age, sex, body mass index (BMI), waist/hip ratio, left ventricular mass index, glycated hemoglobin, fasting plasma insulin and triglyceride concentration, and daily physical activity, FFA concentration and VPCs were significantly correlated (r = 0.21 p <0.01). At multiple logistic regression analysis independently of age, sex, BMI, waist/hip ratio, left ventricular mass index, mean arterial blood pressure, glycated hemoglobin, fasting plasma insulin, triglycerides and potassium concentration, fasting plasma low-density lipoprotein/high-density lipoprotein cholesterol ratio, and daily physical activity, plasma FFA concentration was a significant determinant of VPCs (odds ratio 1.2, 95% confidence interval 1.0 to 2.3). Intralipid infusion (10% in 24 hours) (n = 15) and acipimox administration (250 mg, 4 times/day) (n = 34) increased, and decreased fasting plasma FFA concentration, respectively. In those studies, change in VPCs paralleled the effects on plasma FFA. In the longitudinal study (n = 59), plasma FFA concentration predicted the development of VPCs (RR 1.4 95% confidence interval 1.0 to 1.9) independently of age, sex, BMI, waist/hip ratio, left ventricular mass index, mean arterial blood pressure, fasting plasma triglyceride concentration, fasting plasma low-density lipoprotein/high-density lipoprotein cholesterol ratio, and daily physical activity. In conclusion, in nonischemic patients with non-insulin-dependent diabetes mellitus, plasma FFA concentration is associated with the frequency of ventricular premature complexes.