Natalie Alméras

Hypertriglyceridemic Waist A Marker of the Atherogenic Metabolic Triad (Hyperinsulinemia; Hyperapolipoprotein B; Small, Dense LDL) in Men?

BACKGROUND The present study tested the hypothesis that simple variables, such as waist circumference and fasting plasma triglyceride (TG) concentrations, could be used as screening tools for the identification of men characterized by a metabolic triad of nontraditional risk factors (elevated insulin and apolipoprotein [apo] B and small, dense LDL particles). METHODS AND RESULTS Results of the metabolic study (study 1) conducted on 185 healthy men indicate that a large proportion (>80%) of men with waist circumference values >/=90 cm and with elevated TG levels (>/=2.0 mmol/L) were characterized by the atherogenic metabolic triad. Validation of the model in an angiographic study (study 2) on a sample of 287 men with and without coronary artery disease (CAD) revealed that only men with both elevated waist and TG levels were at increased risk of CAD (odds ratio of 3.6, P<0.03) compared with men with low waist and TG levels. CONCLUSIONS It is suggested that the simultaneous measurement and interpretation of waist circumference and fasting TG could be used as inexpensive screening tools to identify men characterized by the atherogenic metabolic triad (hyperinsulinemia, elevated apo B, small, dense LDL) and at high risk for CAD.

Elevated C-Reactive Protein Another Component of the Atherothrombotic Profile of Abdominal Obesity

Recent studies have suggested that elevated plasma C-reactive protein (CRP) levels are associated with the features of insulin resistance syndrome. In the present study, we have examined the contribution of body composition measured by hydrostatic weighing and of abdominal adipose tissue (AT) accumulation assessed by computed tomography to the variation in plasma CRP levels associated with atherogenic dyslipidemia of the insulin resistance syndrome in a sample of 159 men, aged 22 to 63 years, covering a wide range of adiposity (body mass index values from 21 to 41 kg/m2). Plasma CRP levels showed positive and significant correlations with body fat mass (r =0.41, P <0.0001), waist girth (r =0.37, P <0.0001), and visceral AT accumulation measured by computed tomography at L4 to L5 (r =0.28, P < 0.0003). Although CRP levels were associated with plasma insulin levels measured in the fasting state and after a 75-g oral glucose load, no significant correlations were found with plasma lipoprotein levels. Finally, comparison of body fatness, of abdominal fat accumulation, and of the features of the insulin resistance syndrome across quintiles of CRP revealed major differences in body fatness and in indices of abdominal AT accumulation between the lowest and the highest CRP quintiles, whereas no significant differences were found for variables of the plasma lipoprotein-lipid profile. These results suggest that obesity and abdominal AT accumulation are the critical correlates of elevated plasma CRP levels found in men with atherogenic dyslipidemia of the insulin resistance syndrome.

Acute effects of exercise on energy intake and feeding behaviour

The main objective of the present study was to evaluate the short-term effects of exercise of different intensities on energy intake. Eleven young men were submitted to three randomly assigned sessions (one control and two exercise sessions) in which they ate, ad libitum, foods from a buffet-type meal. The energy cost of exercise was the same in the two exercise sessions. Results showed that there was no significant change in post-exercise subjective levels of hunger and fullness as well as total energy and macronutrient intakes in comparison with the control session. However, when energy intake relative to expenditure was considered by subtracting the surplus of energy expended during exercise from total energy intake, high-intensity exercise exerted a greater reducing effect on this variable compared with the control and low-intensity exercise sessions. These results suggest that for a given level of energy expenditure, high-intensity exercise favours negative energy balance to a greater extent than low-intensity exercise.

Appetite after weight loss by energy restriction and a low-fat diet–exercise follow-up

OBJECTIVE: The aim of the present study was to determine the impact of weight loss on appetite as measured by visual analog scale (VAS).METHODS: Seventeen subjects (10 men and seven women) took part in a 15 week weight loss program which consisted of drug therapy (fenfluramine 60 mg/day) or placebo coupled to an energy restriction (−2930 kJ/day; phase 1) followed by an 18 week low-fat diet–exercise follow-up (phase 2). Subjects were given a standardized breakfast before and after phase 1 as well as after phase 2. Individuals were asked to fill out VAS before and at 0, 10, 20, 30, 40, 50 and 60 min after this test meal. Blood samples were drawn before the meal and at 0, 30 and 60 min postprandially and analyzed for glucose and insulin. Fasting plasma cortisol and leptin were also determined.RESULTS: An increase in the fasting desire to eat, hunger and prospective food consumption (PFC) was observed after phase 1 and to an even greater extent after phase 2 in both men and women. In the fasting state, positive correlations were observed between changes in the desire to eat (r=0.76; P<0.05) as well as changes of PFC (r=0.82; P<0.05) and changes in cortisol at the end of phase 1 for women. In response to phase 1, statistically significant correlations were found between changes of hunger (r=0.64; P<0.05) and desire to eat (r=0.67; P<0.05) as measured by AUC in response to the meal and changes of fasting plasma cortisol in men. The most consistent predictor of changes of baseline desire to eat (r=0.68 P<0.05), fullness (r=−0.78, P<0.05) and PFC (r=0.91, P<0.01) during phase 2 was the change in fasting cortisol in men. Changes of fullness were also associated with changes of fasting leptin in men (r=0.68; P<0.05) during phase 2.CONCLUSION: These results suggest that weight loss is accompanied by an increase of baseline appetite in both men and women and that the most consistent predictor of these changes in appetite seems to be changes in fasting plasma cortisol.

Effect of Rimonabant on the High-Triglyceride/ Low–HDL-Cholesterol Dyslipidemia, Intraabdominal Adiposity, and Liver Fat: The ADAGIO-Lipids Trial

Background—Rimonabant, the first selective cannabinoid type 1 (CB1) receptor antagonist, improves cardiometabolic risk factors in overweight/obese patients. ADAGIO-Lipids assessed the effect of rimonabant on cardiometabolic risk factors and intraabdominal and liver fat. Methods and Results—803 abdominally obese patients with atherogenic dyslipidemia (increased triglycerides [TG] or reduced high-density lipoprotein–cholesterol [HDL-C]) were randomized to placebo or rimonabant 20 mg/d for 1 year. HDL-C and TG were coprimary end points. Intraabdominal (visceral) and liver fat were measured by computed tomography in a subgroup of 231 patients. In total, 73% of rimonabant- and 70% of placebo-treated patients completed the study treatment. Rimonabant 20 mg produced significantly greater changes from baseline versus placebo in HDL-C (+7.4%) and TG levels (−18%; P<0.0001), as well as low-density lipoprotein (LDL) and HDL particle sizes, apolipoprotein A1 and B, HDL2, HDL3, C-reactive protein, and adiponectin levels (all P<0.05). Rimonabant decreased abdominal subcutaneous adipose tissue (AT) cross-sectional area by 5.1% compared to placebo (P<0.005), with a greater reduction in visceral AT (−10.1% compared to placebo; P<0.0005), thereby reducing the ratio of visceral/subcutaneous AT (P<0.05). Rimonabant significantly reduced liver fat content (liver/spleen attenuation ratio; P<0.005). Systolic (−3.3 mm Hg) and diastolic (−2.4 mm Hg) blood pressure were significantly reduced with rimonabant versus placebo (P<0.0001). The safety profile of rimonabant was consistent with previous studies; gastrointestinal, nervous system, psychiatric, and general adverse events were more common with rimonabant 20 mg. Conclusions—In abdominally obese patients with atherogenic dyslipidemia, rimonabant 20 mg significantly improved multiple cardiometabolic risk markers and induced significant reductions in both intraabdominal and liver fat.

Visceral Obesity and Plasma Glucose-Insulin Homeostasis: Contributions of Interleukin-6 and Tumor Necrosis Factor-α in Men

OBJECTIVE This study examined the relationships of two inflammatory cytokines, IL-6 and TNF-alpha, to visceral adiposity and indices of plasma glucose-insulin homeostasis. RESEARCH DESIGN AND METHODS Plasma levels of IL-6 and TNF-alpha were measured in 189 untreated asymptomatic men (aged 43.7 +/- 7.8 yr; body mass index 29.0 +/- 4.3 kg/m(2); waist girth 98.6 +/- 10.3 cm). RESULTS Significant and positive associations were found between both cytokines with adiposity and adipose tissue distribution indices (0.15 < or = r < 0.32; P < 0.05) as well as plasma glucose-insulin homeostasis variables (0.22 < or = r < 0.28; P <0.05). Comparison of two subgroups, each composed of 32 overweight men (> or =25 kg/m(2)) with similar body mass index values (28.7 kg/m(2) in both groups) but with markedly different levels of visceral adipose tissue (< vs. > or = 130 cm(2)), revealed significant differences only for IL-6 levels (1.42 +/- 1.15 vs. 0.86 +/- 0.52 pg/ml; P < 0.02 for men with high vs. low visceral adipose tissue, respectively). Finally, when subjects were stratified on the basis of their respective concentrations of IL-6 and TNF-alpha (using the 50th percentile of their overall distribution), an ANOVA revealed an independent contribution of IL-6 to the variation of fasting insulin (P < 0.01) and each of these two cytokines to the variation of insulin levels measured after a 75-g oral glucose challenge (P <0.01 for IL-6 and P < 0.05 for TNF-alpha). CONCLUSIONS Because IL-6 appeared to be clearly associated with visceral adiposity, TNF-alpha rather showed associations with indices of total body fatness. Thus, TNF-alpha may contribute to the insulin resistance of overall obesity, whereas IL-6 may be one of the mediators of the hyperinsulinemic state specifically related to excess visceral adiposity.

Hypertriglyceridemic waist: A useful screening phenotype in preventive cardiology?

The worldwide increase in the prevalence and incidence of type 2 diabetes represents a tremendous challenge for the Canadian health care system, especially if we consider that this phenomenon may largely be explained by the epidemic of obesity. However, despite the well-recognized increased morbidity and mortality associated with an elevated body weight, there is now more and more evidence highlighting the importance of intra-abdominal adipose tissue (visceral adipose tissue) as the fat depot conveying the greatest risk of metabolic complications. In this regard, body fat distribution, especially visceral adipose tissue accumulation, has been found to be a key correlate of a cluster of diabetogenic, atherogenic, prothrombotic and inflammatory metabolic abnormalities now often referred to as the metabolic syndrome. This dysmetabolic profile is predictive of a substantially increased risk of coronary artery disease (CAD) even in the absence of hyperglycemia, elevated low-density lipoprotein cholesterol or hypertension. For instance, some features of the metabolic syndrome (hyperinsulinemia, elevated apolipoprotein B and small low-density lipoprotein particles--the so-called atherogenic metabolic triad) have been associated with a more than 20-fold increase in the risk of ischemic heart disease in middle-aged men enrolled in the Quebec Cardiovascular Study. This cluster of metabolic complications has also been found to be predictive of a substantially increased risk of CAD beyond the presence of traditional risk factors. These results emphasize the importance of taking into account in daily clinical practice the presence of metabolic complications associated with abdominal obesity together with traditional risk factors to properly evaluate the cardiovascular risk profile of patients. From a risk assessment standpoint, on the basis of additional work conducted by several groups, there is now evidence that the simultaneous presence of an elevated waist circumference and fasting triglyceride levels (a condition that has been described as hypertriglyceridemic waist) may represent a relevant first-step approach to identify a subgroup of individuals at higher risk of being carriers of the features of the metabolic syndrome. Moreover, a moderate weight loss in initially abdominally obese patients is associated with a selective mobilization of visceral adipose tissue, leading to improvements in the metabolic risk profile predictive of a reduced risk of CAD and type 2 diabetes. In conclusion, hypertriglyceridemic waist as a marker of visceral obesity and related metabolic abnormalities is a useful and practical clinical phenotype to screen persons at risk for CAD and type 2 diabetes.

Evidence for the existence of adaptive thermogenesis during weight loss

The present study was performed to further investigate the adaptive component of thermogenesis that appears during prolonged energy restriction. Fifteen obese men and twenty obese women underwent a 15-week weight-loss programme. During this programme, body weight and composition as well as resting energy expenditure (REE) were measured at baseline, after 2 and 8 weeks of energy restriction (-2929 kJ/d) and drug therapy (or placebo), and finally 2-4 weeks after the end of the 15-week drug therapy and energy restriction intervention, when subjects were weight stable. Regression equations were established in a control population of the same age. These equations were then used to predict REE in obese men and women at baseline, after 2 and 8 weeks, as well as after the completion of the programme. In both men and women body weight and fat mass were significantly reduced in all cases) while fat-free mass remained unchanged throughout the programme. At baseline, REE predicted from the regression equation was not significantly different from the measured REE in men, while in women the measured REE was 13 % greater than predicted. After 2 weeks of energy restriction, measured REE had fallen by 469 and 635 kJ/d more than predicted and this difference reached 963 and 614 kJ/d by week 8 of treatment in men and women respectively. Once body-weight stability was recovered at the end of the programme, changes in REE remained below predicted changes in men (-622 kJ/d). However, in women changes in predicted and measured REE were no longer different at this time, even if the women were maintaining a reduced body weight. In summary, the present results confirm the existence of adaptive thermogenesis and give objective measurements of this component during weight loss in obese men and women, while they also emphasize that in women this component seems to be essentially explained by the energy restriction.

Impact of high-intensity exercise on energy expenditure, lipid oxidation and body fatness

OBJECTIVE: Two studies were conducted to assess the potential of an increase in exercise intensity to alter energy and lipid metabolism and body fatness under conditions mimicking real life.METHODS: Study 1 was based on the comparison of adiposity markers obtained in 352 male healthy adults who participated in the Québec Family Study who either regularly participated in high-intensity physical activities or did not. Study 2 was designed to determine the effects of high-intensity exercise on post-exercise post-prandial energy and lipid metabolism as well as the contribution of β-adrenergic stimulation to such differences under a real-life setting.RESULTS: Results from Study 1 showed that men who regularly take part in intense physical activities display lower fat percentage and subcutaneous adiposity than men who never perform such activities, and this was true even if the latter group reported a lower energy intake (917 kJ/day, P<0.05). In Study 2, the high-intensity exercise stimulus produced a greater post-exercise post-prandial oxygen consumption as well as fat oxidation than the resting session, an effect which disappeared with the addition of propranolol. In addition, the increase in post-prandial oxygen consumption observed after the high-intensity exercise session was also significantly greater than that promoted by the low-intensity exercise session.CONCLUSION: These results suggest that high-intensity exercise favors a lesser body fat deposition which might be related to an increase in post-exercise energy metabolism that is mediated by β-adrenergic stimulation.

Visceral Adipose Tissue Indicates the Severity of Cardiometabolic Risk in Patients with and without Type 2 Diabetes: Results from the INSPIRE ME IAA Study

BACKGROUND Visceral adiposity is an important correlate of cardiometabolic risk, yet its association after the diagnosis of type 2 diabetes remains unclear. METHODS Our objective was to assess the independent and combined associations of visceral adiposity and type 2 diabetes to cardiometabolic risk. The INternational Study of Prediction of Intra-abdominal adiposity and its RElationships with cardioMEtabolic risk/Intra-Abdominal Adiposity (INSPIRE ME IAA) is a cross-sectional computed tomography imaging study with data collected from June 2006 to May 2008. General physicians, cardiologists, and diabetologists (n = 297) in 29 countries recruited 4144 (51.8% men) men (39-71 yr) and women (44-71 yr). Patients were categorized according to visceral adiposity tertiles, type 2 diabetes status, and sex. All results were adjusted for age, body mass index, region, and physicians specialty. RESULTS Markers of insulin resistance, lipid/lipoproteins, inflammatory markers, and liver fat increased with visceral adiposity in men and women with and without type 2 diabetes. Prevalent cardiovascular disease increased with visceral adiposity tertiles, regardless of type 2 diabetes status. Visceral adiposity [odds ratio = 1.25 (1.09-1.44) for men and 1.78 (1.50-2.12) for women] was positively associated with type 2 diabetes, whereas liver attenuation (inversely related to liver fat) was negatively associated with type 2 diabetes [odds ratio = 0.66 (0.59-0.75) for men and 0.63 (0.55-0.72) for women]. Subcutaneous adipose tissue was inversely related to type 2 diabetes in women [0.76 (0.0.66-0.88)] and not associated with type 2 diabetes in men [0.97 (0.85-1.11)]. CONCLUSIONS Visceral, but not sc, abdominal adiposity is strongly related to cardiometabolic risk factors and to the prevalence of cardiovascular disease and may be an important driver of cardiometabolic risk in patients regardless of type 2 diabetes status.