Postprandial hyperlipidemia: another correlate of the "hypertriglyceridemic waist" phenotype in men.

Fasting hypertriglyceridemia has been reported to be predictive of an exaggerated triglyceride (TG) response to an oral fat load. Abdominal obesity has also been associated with postprandial hyperlipidemia. The objective of the present study was to quantify the contribution of abdominal obesity and fasting hypertriglyceridemia to the magnitude of postprandial lipemia. For that purpose, potential differences in postprandial TG-rich lipoprotein (TRL) levels were examined among men characterized by the absence/presence of the "hypertriglyceridemic waist" phenotype following a standardized breakfast with a high fat content (64% calories as fat). Sixty-nine men (mean age +/- S.D.: 45.1 +/- 10.5 years) were classified according to waist girth (< 90 or >/ or = 90 cm) and fasting TG concentrations (< 2.0 or > or = 2.0 mmol/l). Subjects characterized by "hypertriglyceridemic waist" (waist > or = 90 cm and fasting TG > or = 2.0 mmol/l) showed the highest TRL-TG concentrations (P < 0.0001) throughout the entire postprandial period (8 h) as well as elevated concentrations of apolipoprotein (apo) B-48 and apo B-100 in all TRL fractions (large, medium and small) compared to subjects with low fasting TG levels who had waist girth values either above or below 90 cm. These higher postprandial TRL-TG levels among carriers of the "hypertriglyceridemic waist" phenotype also led to significantly greater postprandial TG-total area under the curve (AUC) in total TRLs resulting mainly from the increased concentrations of large- and medium-sized TRLs. Furthermore, subjects characterized by the "hypertriglyceridemic waist" phenotype displayed higher fasting insulin concentrations and postprandial insulin AUC compared to men with low fasting plasma TG levels and low waist girth values. In conclusion, results of the present study indicate that postprandial hyperlipidemia is associated with the simultaneous presence of abdominal obesity and elevated fasting TG concentrations: a condition that we have described as the "hypertriglyceridemic waist" phenotype.

Impact of postprandial variation in triglyceridemia on low-density lipoprotein particle size.

The fasting atherogenic dyslipidemia of visceral obesity, which includes the presence of small, dense low-density lipoprotein (LDL) particles, is predictive of an increased risk of coronary heart disease (CHD). It has also been suggested that progression of atherosclerosis may be accelerated in the presence of postprandial hyperlipidemia independently from the fasting dyslipidemic state. Studies have shown that the best predictor of postprandial hyperlipidemia and of the small, dense LDL phenotype is fasting triglyceride (TG) concentration. In the present study, we evaluated the impact of postprandial hypertriglyceridemia on the variation in LDL particle size. Fasting (0 hour) and postprandial changes (2, 4, 6, and 8 hours) in LDL particle size were measured by nondenaturing 2% to 16% polyacrylamide gel electrophoresis in a sample of 49 men (mean age +/- SD: 46.6 +/- 9.2 years) who underwent a standardized breakfast with a high-fat (64% calories as fat) content. The postprandial increase in TG levels was associated with a transient reduction in LDL particle size, the most substantial reduction being observed 4 hours (-1.0 +/- 2.4 A) after the oral fat load. Although there were strong correlations between TG-rich lipoprotein (TRL)-TG levels and LDL particle size in the fasting state (r=-0.71, P<.0001) as well as 4 hours after the oral fat load (r=-0.70, P<.0001), changes in TRL-TG concentrations during the postprandial state (from time 0 to 4 hours) were not associated with changes in LDL particle size during this period (r=-0.04, not significant [NS]). However, among subgroups of men matched for similar fasting TRL-TG levels (n=12), subjects with the highest total area under the curve (AUC) of TRL-TG after the fat load were characterized by smaller LDL particle size at 6 and 8 hours compared with men with the lowest AUC TRL-TG (P<.02). Men displaying the highest postprandial AUC TRL-TG were also characterized by the greatest accumulation of visceral adipose tissue (AT) (P<.05). These results indicate that the hypertriglyceridemic (hyperTG) state induced by a high-fat meal is associated with a transient reduction in LDL peak particle diameter, which is not proportionate, however, to the level of TG achieved in the postprandial state. Furthermore, despite similar TG levels at baseline, viscerally obese men with an impaired postprandial lipemia had smaller LDL particles at the end of the oral fat load than obese men with a lower accumulation of visceral AT.

Contribution of visceral adiposity to the exaggerated postprandial lipemia of men with impaired glucose tolerance.

OBJECTIVE: Impaired glucose tolerance (IGT) has been associated with alterations in numerous coronary heart disease risk factors, including postprandial hyperlipidemia. An excess visceral adipose tissue accumulation is also predictive of IGT and of an exaggerated postprandial lipemia. The objective of the present study was therefore to compare the respective contributions of visceral adipose tissue accumulation versus IGT with the variation in postprandial lipemia. RESEARCH DESIGN AND METHODS: Potential differences in postprandial triglyceride (TG)-rich lipoprotein (TRL) levels following a standardized breakfast with a high fat content were examined among men characterized by normal glucose tolerance (NGT) or IGT. Sixty-seven men were classified according to their glucose tolerance status (<7.8 mmol/l [NGT] or between 7.8 and 11.1 mmol/l [IGT] 2 h after a 75-g oral glucose test). RESULTS: Men with IGT showed the highest TRL-TG concentrations (P < 0.05) at the 4-, 6-, and 8-h time points compared with men with NGT. These higher postprandial TRL-TG levels among men with IGT were also accompanied by a greater postprandial TG total area under the incremental curve in all TRL fractions (large, medium, and small) (P < 0.05). Furthermore, subjects characterized by IGT had also the highest visceral adipose tissue accumulation (P < 0.009). When subgroups of IGT and NGT men were individually matched (n = 11) for similar visceral adipose tissue accumulation, no significant difference was found in postprandial responses of all TRL-TG fractions between the two groups. CONCLUSIONS: These results provide evidence that visceral adipose tissue accumulation is an important factor involved in the deterioration of postprandial lipemia noted among men with IGT.

Effects of prednisone withdrawal on the new metabolic triad in cyclosporine-treated kidney transplant patients.

BACKGROUND: Cardiovascular disease is a major cause of morbidity and mortality after renal transplantation. Prednisone (Pred) maintenance therapy is associated with risk factors for atherosclerosis. Therefore, we were interested in quantifying the effects of Pred withdrawal on body weight and waist circumference as well as on metabolic markers of coronary heart disease risk. METHODS: Twenty-six cyclosporine-treated renal transplant patients (13 men and 13 women) were evaluated before and after at least 11 months (16 +/- 2.9 months) of Pred withdrawal. A complete fasting lipoprotein-lipid profile as well as anthropometric measurements were obtained from each patient. RESULTS: Pred withdrawal was associated with a 6.0% reduction of body weight (-4.34 +/- 5.40 kg; P < 0.05) and with a 7.7% decrease in waist girth (-7.13 +/- 5.75 cm; P < 0.005) in women, whereas no change in these variables were observed in men. In both genders, plasma low-density lipoprotein (LDL) cholesterol and triglyceride concentrations were unaffected by Pred withdrawal, whereas plasma high-density lipoprotein (HDL) cholesterol levels decreased by 14.0% in women (-0.22 +/- 0.22 mmol/L; P < 0.005) and 22.0% in men (-0.36 +/- 0.28 mmol/L; P < 0.005). Pred withdrawal was associated with a significant reduction in plasma apolipoprotein B concentrations in both women (-0.28 +/- 0.15 g/L; -24.6%; P < 0.0001) and men (-0.22 +/- 0.19 g/L; -20.5%; P < 0.005). A significant reduction in fasting insulin was observed in both women (-27.8 +/- 27.9 pmol/L; -25.3%; P < 0.005) and men (-25.0 +/- 32.8 pmol/L; -21.4%; P < 0.05), whereas the LDL peak particle size was unaffected by Pred withdrawal. CONCLUSIONS: Pred withdrawal modifies several anthropometric and metabolic cardiovascular risk factors in renal transplant patients. Furthermore, female patients may derive further benefits of Pred withdrawal resulting from the concomitant loss of body weight and abdominal fat.

Influences of the PPAR alpha-L162V polymorphism on plasma HDL(2)-cholesterol response of abdominally obese men treated with gemfibrozil.

PURPOSE: The effect of gemfibrozil is mediated by the activation of peroxisome proliferator-activated receptor alpha (PPAR alpha). The objective of this study was to determine whether the lipid response to gemfibrozil therapy is influenced by the PPAR alpha-L162V polymorphism. METHODS: Sixty-three abdominally obese men were randomly assigned to a 6-month-intervention program with either receiving a placebo (N = 31) or gemfibrozil (N = 32). RESULTS: In response to gemfibrozil therapy, L162-homozygotes exhibited a 5.5% increase in high-density lipoprotein 2 cholesterol (HDL(2)-C) levels compared with a 50.0% increase among carriers of the V162 allele (P = 0.03). CONCLUSION: These results suggest that the HDL(2)-C response to gemfibrozil is modulated by the PPAR alpha-L162V polymorphism.

Evidence for impaired lipolysis in abdominally obese men: postprandial study of apolipoprotein B-48- and B-100-containing lipoproteins.

BACKGROUND: Abdominal obesity has been associated with postprandial hypertriglyceridemia. The contribution of intestinally and hepatically derived lipoproteins to this exaggerated postprandial lipemic response is not known. OBJECTIVE: We examined the associations between body fatness, fat distribution, and postprandial apolipoprotein (apo) B-48 and apo B-100 concentrations measured in triacylglycerol-rich lipoproteins (TRLs). DESIGN: Dietary fat tolerance was investigated in 50 men aged 28-67 y. The subjects were given a test meal containing 60 g fat/m(2) body surface area and providing 64% of energy from fat, 18% from carbohydrates, and 18% from protein. The meal provided 7524-9196 kJ, depending on body surface area. Blood samples were collected every 2 h over an 8-h period. RESULTS: The increase in plasma triacylglycerol after the meal resulted from increases in both apo B-48- and apo B-100-containing lipoproteins. The apo B-100 concentration was the strongest contributor (R(2) = 69.6%, P = 0.0001) to postprandial triacylglycerol in total TRLs; the postprandial increase in triacylglycerol was best predicted by the apo B-48 concentration (R(2) = 32.7%, P = 0.0001). Visceral abdominal fat was significantly associated with high postprandial TRL apo B-48 and apo B-100 concentrations (r = 0.30-0.44, P < 0.05). After the meal, the apo B-100 concentration in small TRLs decreased in 12 subjects. These men showed features of the insulin resistance-dyslipidemic syndrome, including more visceral fat (P = 0.07) and an altered fasting metabolic profile. CONCLUSION: A lower lipolytic capacity may contribute to the exaggerated and prolonged postprandial lipemia among abdominally obese men.

Determinants of HDL particle size in patients with the null (P207L) or defective (D9N) mutation in the lipoprotein lipase gene: the Québec LipD Study.

The aim of the present study was to examine the impact of the defective D9N and the null P207L mutations in the lipoprotein lipase (LPL) gene on high density lipoprotein (HDL) particle size in relation to specific environmental factors such as obesity, gender and menopausal status. Analyses were carried out in 118 heterozygous carriers of the D9N mutation and 88 heterozygous for the P207L mutation. HDL particle size was measured on whole plasma by non-denaturing 4-30% polyacrylamide gradient gel electrophoresis. Although carriers of the P207L mutation presented a more deteriorated lipoprotein-lipid profile compared with carriers of the D9N mutation, there was no difference in HDL particle size between the P207L and D9N carriers (81.9+/-4.5 vs. 82.7+/-4.4 A, respectively, P=0.2). Multivariate analyses indicated that waist circumference (P=0.001) and HDL cholesterol levels (P<0.001) were independent predictors of HDL particle size among carriers of the defective D9N mutation. On the other hand, gender (P=0.03), plasma cholesterol (P=0.01) and TG (P=0.04) levels were significant predictors of HDL particle size among carriers of the null P207L mutation in multivariate analyses. These results suggest that the nature of the mutation in the LPL gene modifies the relationship of HDL particle size to other metabolic variables and secondary factors such as abdominal obesity and gender.

HDL particle size: a marker of the gender difference in the metabolic risk profile.

A low plasma HDL-cholesterol concentration is an important risk factor for coronary heart disease (CHD) and is often accompanied by increased triglyceride concentrations. Women have generally higher HDL-cholesterol and lower triglyceride concentrations and concomitantly are at lower risk of CHD than men. As HDL particle size is a new and potentially important marker of CHD risk, we have examined the potential gender difference in HDL particle size, assessed by nondenaturing 4-30% polyacrylamide gradient gel electrophoresis, in a sample of men (n=231) and women (n=183). Overall, men were characterized by a less favorable lipoprotein--lipid profile, which was accompanied by smaller HDL particle size compared to women. However, when men and women were matched for HDL particle size and compared for their metabolic profile, it was found that both genders were characterized by similar plasma lipoprotein--lipid profile despite the fact that women were characterized by higher levels of total body fat but lower waist girth than men. In summary, HDL particle size is a strong marker of the gender-related difference in the determination of the metabolic risk profile.