Agnès Pascot

Effect of a low-glycaemic index -low-fat-high protein diet on the atherogenic metabolic risk profile of abdominally obese men

It has been suggested that the current dietary recommendations (low-fat-high-carbohydrate diet) may promote the intake of sugar and highly refined starches which could have adverse effects on the metabolic risk profile. We have investigated the short-term (6-d) nutritional and metabolic effects of an ad libitum low-glycaemic index-low-fat-high-protein diet (prepared according to the Montignac method) compared with the American Heart Association (AHA) phase I diet consumed ad libitum as well as with a pair-fed session consisting of the same daily energy intake as the former but with the same macronutrient composition as the AHA phase I diet. Twelve overweight men (BMI 33.0 (sd 3.5) kg/m2) without other diseases were involved in three experimental conditions with a minimal washout period of 2 weeks separating each intervention. By protocol design, the first two conditions were administered randomly whereas the pair-fed session had to be administered last. During the ad libitum version of the AHA diet, subjects consumed 11695.0 (sd 1163.0) kJ/d and this diet induced a 28 % increase in plasma triacylglycerol levels (1.77 (sd 0.79) v. 2.27 (sd 0.92) mmol/l, P<0.05) and a 10 % reduction in plasma HDL-cholesterol concentrations (0.92 (sd 0.16) v. 0.83 (sd 0.09) mmol/l, P<0.01) which contributed to a significant increase in cholesterol:HDL-cholesterol ratio (P<0.05), this lipid index being commonly used to assess the risk of coronary heart disease. In contrast, the low-glycaemic index-low-fat-high-protein diet consumed ad libitum resulted in a spontaneous 25 % decrease (P<0.001) in total energy intake which averaged 8815.0 (sd 738.0) kJ/d. As opposed to the AHA diet, the low-glycaemic index-low-fat-high-protein diet produced a substantial decrease (-35 %) in plasma triacylglycerol levels (2.00 (sd 0.83) v. 1.31 (sd 0.38) mmol/l, P<0.0005), a significant increase (+1.6 %) in LDL peak particle diameter (251 (sd 5) v. 255 (sd 5) A, P<0.02) and marked decreases in plasma insulin levels measured either in the fasting state, over daytime and following a 75 g oral glucose load. During the pair-fed session, in which subjects were exposed to a diet with the same macronutrient composition as the AHA diet but restricted to the same energy intake as during the low-glycaemic index-low-fat-high-protein diet, there was a trend for a decrease in plasma HDL-cholesterol levels which contributed to the significant increase in cholesterol:HDL-cholesterol ratio noted with this condition. Furthermore, a marked increase in hunger (P<0.0002) and a significant decrease in satiety (P<0.007) were also noted with this energy-restricted diet. Finally, favourable changes in the metabolic risk profile noted with the ad libitum consumption of the low-glycaemic index-low-fat-high-protein diet (decreases in triacyglycerols, lack of increase in cholesterol:HDL-cholesterol ratio, increase in LDL particle size) were significantly different from the response of these variables to the AHA phase I diet. Thus, a low-glycaemic index-low-fat-high-protein content diet may have unique beneficial effects compared with the conventional AHA diet for the treatment of the atherogenic metabolic risk profile of abdominally obese patients. However, the present study was a short-term intervention and additional trials are clearly needed to document the long-term efficacy of this dietary approach with regard to compliance and effects on the metabolic risk profile.

Contribution of visceral obesity to the deterioration of the metabolic risk profile in men with impaired glucose tolerance.

Aims/hypothesis. Impaired glucose tolerance is associated with metabolic alterations which increase cardiovascular disease risk. The contribution of hyperglycaemia to this increased risk is, however, not clear. Abdominal obesity is often observed in subjects with impaired glucose tolerance; our objective was therefore to find the contribution of visceral adipose tissue to the deterioration of the metabolic risk profile noted in subjects with impaired glucose tolerance. Methods. We studied 284 men with a normal glucose tolerance and 66 men with impaired glucose tolerance which was defined as a glycaemia between 7.8 and 11.1 mmol/l 2 h after a 75-g glucose load. Results. Men with impaired glucose tolerance had more visceral adipose tissue and higher concentrations of plasma glucose and insulin in the fasting state and following a 75-g oral glucose load than men with a normal glucose tolerance. They also had higher concentrations of plasma cholesterol, triglycerides, apolipoprotein B and lower concentrations of HDL-cholesterol as well as higher cholesterol:HDL-cholesterol ratios than men with a normal glucose tolerance. The two groups of men were then compared after a statistical adjustment for the amount of visceral adipose tissue. Although men with impaired glucose tolerance still had higher fasting plasma glucose and insulin concentrations after the adjustment for visceral adipose tissue, differences in all the variables of the lipid-lipoprotein profile were eliminated. Conclusion/interpretation. Visceral adipose tissue accumulation is an important factor in the deterioration of the plasma lipid-lipoprotein noted in men with impaired glucose tolerance. [Diabetologia 2000 43: 1126–1135]

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.

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.

The small, dense LDL phenotype as a correlate of postprandial lipemia in men

The atherogenic dyslipidemia of the insulin resistance syndrome is characterized by hypertriglyceridemia (hyperTG), elevated apolipoprotein (apo) B levels, reduced high-density lipoprotein (HDL) cholesterol concentrations and by an increased proportion of small, dense low-density lipoprotein (LDL) particles. Although the hyperTG-low HDL cholesterol dyslipidemia has been associated with an impaired clearance of dietary fat, the contribution of the small, dense LDL phenotype as an independent predictor of postprandial triglyceride (TG) clearance remains uncertain. We have therefore compared the postprandial TG response among three subgroups of men characterized by small, intermediate or large LDL particles in a total sample of 69 men (mean age +/- SD; 45.1 +/- 10.5 years). To identify men with small versus large LDL particles, the first (LDL peak particle diameter < 251.9 A) and the third (> 257.6 A) tertiles of the distribution of LDL particle diameters were used as cutoff points. Men with small, dense LDL particles had the expected fasting dyslipidemic profile (high TG-low HDL cholesterol levels) compared to men with large, buoyant LDL particles. The oral lipid tolerance test revealed that men with small, dense LDL particles had significantly higher total-, large-, and medium-TG-rich lipoprotein (TRL) responses to a fatty meal than men with large LDL particles (P < 0.03). In addition, within a subgroup of normolipidemic men (TG < 2.3 mmol/l and HDL cholesterol > 0.9 mmol/l), those with small, dense LDL particles had higher levels of total-, medium- and small-TRL responses compared to men with large, buoyant LDL particles (P < 0.05). Moreover, normotriglyceridemic men with small, dense LDL had higher levels of small-TRLs measured 8 h after the ingestion of the fat meal (P < 0.05) compared to normolipidemic men with large, buoyant LDL particles. Results of the present study suggest that the dense LDL phenotype may be an additional fasting marker of an exaggerated postprandial TG response and of an impaired clearance of TRLs.

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 (PPARα). The objective of this study was to determine whether the lipid response to gemfibrozil therapy is influenced by the PPARα-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 (HDL2-C) levels compared with a 50.0% increase among carriers of the V162 allele (P = 0.03).Conclusion: These results suggest that the HDL2-C response to gemfibrozil is modulated by the PPARα-L162V polymorphism.

Visceral adipose tissue and low-density lipoprotein particle size in middle-aged versus young men

Age is associated with increased deposition of visceral adipose tissue. We examined whether this age-related change in regional adipose tissue distribution had an impact on low-density lipoprotein (LDL) particle size. For this purpose, the plasma lipoprotein-lipid profile, including LDL peak particle diameter as determined by gradient gel electrophoresis, was assessed in 38 young men (aged 26.4 +/- 4.2 years, mean +/- SD) and compared with 40 middle-aged men (55.9 +/- 6.2 years). Middle-aged men had higher values for total body fat and visceral adipose tissue area as measured by computed tomography than young men (P < .001). Although significant differences were noted between the two age groups for plasma cholesterol, triglyceride (TG), apolipoprotein B (apo B), LDL cholesterol, and LDL apo B, as well as the cholesterol to high-density lipoprotein (HDL) cholesterol ratio (P < .001), no difference was found for LDL peak particle size between young and middle-aged men. While visceral adipose tissue was a significant correlate of plasma lipoprotein levels, the fasting TG concentration was the best predictor of LDL particle size, and the regression of TG levels on LDL peak particle diameter was not different between the two age groups. These results suggest that middle-aged men are characterized by an increased concentration of LDL particles (reflected by increased LDL apo B levels) but not by a reduced LDL peak particle size compared with young men. It is therefore proposed that in the absence of an important age-related change in TG levels, age per se is associated with an increased concentration of atherogenic LDL particles rather than a reduction of LDL particle diameter.

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.