Denis Prud’homme

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

BACKGROUNDnThe 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).nnnMETHODS AND RESULTSnResults 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.nnnCONCLUSIONSnIt 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.

The Lipoprotein Lipase HindIII Polymorphism Modulates Plasma Triglyceride Levels in Visceral Obesity

The aim of this study was to investigate the potential interaction between the lipoprotein lipase (LPL) HindIII polymorphism and visceral adipose tissue (AT) accumulation in the modulation of triglyceride levels in visceral obesity. The LPL-HindIII genotype was determined by polymerase chain reaction in 52 min. Twenty-three subjects were heterozygous (+/-) and 28 were homozygous (+/+) for the presence of the restriction site. One subject who was homozygous for the--allele was excluded from analysis. Body mass index (BMI), fasting insulin level, and visceral AT area as measured by computed tomography were positively correlated with triglyceride levels only in subjects homozygous for the + allele. Furthermore, whereas these variables were negatively correlated with plasma HDL2 cholesterol concentrations in the +/+ group, these associations were not found in +/- heterozygotes, with the exception of BMI. To further investigate the interaction of the LPL-HindIII polymorphism with visceral obesity and hyperinsulinemia, the two genotype groups were further subdivided on the basis of BMI (low versus high), fasting insulin level (low versus high), and visceral AT area (low versus high), and their lipoprotein profiles were compared. Elevated levels of abdominal visceral AT were significantly associated with increased triglyceride concentrations in +/+ homozygous men, suggesting that visceral obesity may lead to hypertriglyceridemia in the presence of the +/+ genotype. In the +/- group, variation in the amount of visceral AT was not associated with differences in triglyceride concentration. However, hypertriglyceridemia and an increased cholesterol-to-HDL cholesterol ratio were observed in the hyperinsulinemic state irrespective of LPL-HindIII genotype status.(ABSTRACT TRUNCATED AT 250 WORDS)

Gemfibrozil Reduces Plasma C-Reactive Protein Levels in Abdominally Obese Men With the Atherogenic Dyslipidemia of the Metabolic Syndrome

To the Editor:nnRecent data from Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial (VA-HIT) have recently reported that pharmacological treatment with a fibrate (gemfibrozil) significantly reduced coronary heart disease (CHD) risk among men with a history of CHD who had low HDL-cholesterol and LDL-cholesterol levels at baseline evaluation.1 Moreover, this study also demonstrated that changes in the lipoprotein-lipid profile only partially explained the beneficial effect of gemfibrozil on CHD risk, suggesting that other factors may be responsible for the reduction in the risk of CHD observed among patients undergoing fibrate therapy.2nnOn the other hand, the contribution of inflammation to the development of atherosclerosis and CHD is increasingly recognized, and recent studies have identified some inflammatory markers, such as plasma C-reactive protein (CRP) and cytokines, as CHD risk factors.3,4 ⇓ Recent data have suggested that statins and fibrates may favorably decrease markers of inflammation.5–8 ⇓ ⇓ ⇓nnHowever, the effect of fibrates among abdominally obese men with the atherogenic dyslipidemia of the metabolic syndrome (a condition associated with markedly elevated inflammatory markers) has, to the best of our knowledge, never been reported. Thus, the aim of the present study was to examine the effect of a 6-month fibrate treatment on plasma CRP concentrations and cytokine levels such as interleukin …

Effects of a 6-month caloric restriction induced-weight loss program in obese postmenopausal women with and without the metabolic syndrome: a MONET study

Objective: To compare the effects of a caloric restriction (CR) on body composition, lipid profile, and glucose homeostasis in obese postmenopausal women with and without metabolic syndrome (MetS). Methods: Secondary analyses were performed on 73 inactive obese postmenopausal women (age 57.7u200a±u200a4.8 years; body mass index 32.4u200a±u200a4.6u200akg/m2) who participated in the 6-month CR arm of a study of the Montreal-Ottawa New Emerging Team. The harmonized MetS definition was used to categorize participants with MetS (nu200a=u200a20, 27.39%) and without MetS (nu200a=u200a53, 72.61%). Variables of interest were: body composition (dual-energy X-ray absorptiometry), body fat distribution (computed tomography scan), glucose homeostasis at fasting state and during a euglycemic/hyperinsulinemic clamp, fasting lipids, and resting blood pressure. Results: By design, the MetS group had a worse cardiometabolic profile, whereas both groups were comparable for age. Fifty-five participants out of 73 displayed no change in MetS status after the intervention. Twelve participants out of 20 (or 60.0%) in the MetS group had no more MetS after weight loss (Pu200a=u200aNS), whereas 6 participants out of 53 (or 11.3%) in the other group developed the MetS after the intervention (Pu200a=u200aNS). Overall, indices of body composition and body fat distribution improved significantly and similarly in both groups (P between 0.03 and 0.0001). Furthermore, with the exception of triglyceride levels and triglycerides/high-density lipoprotein cholesterol ratio, which decrease significantly more in the MetS group (Pu200a⩽u200a0.05), no difference was observed between groups for the other variables of the cardiometabolic profile. Conclusions: Despite no overall significant effects on MetS, heteregeneous results were obtained in response to weight loss in the present study, with some improving the MetS, whereas other displaying deteriorations. Further studies are needed to identify factors and phenotypes associated with positive and negative cardiometabolic responses to CR intervention.

Effect of the menopausal transition and physical activity energy expenditure on inflammatory markers: a MONET group study.

Objective:Menopausal transition is usually associated with changes in body composition and a decrease in physical activity energy expenditure. Adipose tissue, especially visceral fat, is an important source of inflammatory markers, which contributes to the development of a proinflammatory state. Conversely, high levels of physical activity and exercise have an anti-inflammatory effect. This study aimed to investigate the impact of menopausal transition and physical activity on inflammatory makers. Methods:One hundred two healthy premenopausal women participated in a 5-year longitudinal study. The present secondary analyses were performed on 58 participants with a full set of data (age: 49.6u200a±u200a1.7u200ay; body mass index: 23.3u200a±u200a2.4u200akg/m2). Measures included body composition, waist circumference, fasting glucose and insulin levels, insulin sensitivity, plasma lipid levels, cardiorespiratory fitness, physical activity energy expenditure, and inflammatory markers. Results:Repeated measure analyses revealed, after the 5-year follow-up, significant increases in ferritin, interleukin-8 (IL-8), and soluble tumor necrosis factor-&agr; receptor 1 and 2 (sTNFR1 and sTNFR2) (Pu200a<u200a0.001), and a significant decrease in serum high-sensitive C-reactive protein (Pu200a<u200a0.05). Positive correlations were observed between change (year 5 to baseline) in waist circumference and changes in high-sensitive C-reactive protein, orosomucoid (ORM), haptoglobin, and apolipoprotein B (ApoB) levels (0.26 ⩽ r ⩽ 0.34; Pu200a<u200a0.05), and between change in peripheral fat and changes in ORM, ApoB, sTNFR2 (0.28 ⩽ r ⩽ 0.39; Pu200a<u200a0.05). On the contrary, negative correlations were found between change in physical activity energy expenditure and changes in ORM as well as ApoB (ru200a=u200a−0.35 and ru200a=u200a−0.36, respectively; Pu200a<u200a0.05). No significant correlations were found between change in cardiorespiratory fitness, glucose, insulin, insulin sensitivity and changes in inflammatory markers. Multiple regression analyses showed that changes in physical activity energy expenditure and waist circumference together explained 23% of the individual variance of change in ORM (Pu200a<u200a0.05). Also, change in physical activity energy expenditure explained 15% (Pu200a<u200a0.05) of the variance of change in ApoB. Fat mass change explained 15% (Pu200a<u200a0.05) of the variance of change in IL-8, and finally change in peripheral fat explained 15% of variance of change in sTNFR2 (Pu200a<u200a0.05). Conclusions:The present study indicates that the menopausal transition is accompanied by an increase in inflammatory markers, namely ferritin, IL-8, sTNFR1, and sTNFR2. The increase in IL-8 and sTNFR2 with menopause could be explained, in part, by changes in fat mass and peripheral fat, respectively.

Body composition, cardiometabolic risk factors, physical activity, and inflammatory markers in premenopausal women after a 10-year follow-up: a Monet study

Objective: Menopausal transition and postmenopause are usually associated with changes in body composition and a decrease in physical activity energy expenditure (PAEE). This study investigated body composition, cardiometabolic risk factors, PAEE, and inflammatory markers in premenopausal women after a 10-year follow-up. Methods: In all, 102 premenopausal women participated in the 5-year observational longitudinal Montreal Ottawa New Emerging Team (MONET) study. This present substudy included 48 participants (age: 60.0u200a±u200a1.7 years; body mass index: 23.2u200a±u200a2.2u200akg/m2) 6.0u200a±u200a0.3 years after completion of the initial MONET study. Measures included body composition, waist circumference (WC), fasting glucose and insulin levels, insulin sensitivity (QUICKI model), plasma lipid levels, PAEE, and inflammatory markers. Results: Compared with baseline measures of the MONET study, analyses revealed no significant increase in body weight, although there were significant increases in WC, fat mass (FM), % FM, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol, haptoglobin, apolipoprotein B, ferritin, adiponectin, and soluble cluster of differentiation 14 (all Pu200a<u200a0.001) after the 10-year follow-up. However, significant decreases were observed for fat-free mass, PAEE, fasting glucose levels, interleukin-8 levels, and soluble tumor necrosis factor receptors 1 and 2 (sTNFR-1 and sTNFR-2) levels (all Pu200a<u200a0.05). To determine the effect of postmenopausal years, data were restructured based on final menstrual period (FMP), and one-way analyses of variance were performed. Waist circumference, % FM, total cholesterol, high-density lipoprotein cholesterol, apolipoprotein B, ferritin, adiponectin, and soluble cluster of differentiation 14 were higher in early and late postmenopausal periods in these women. sTNFR-1 and sTNFR-2 levels were higher at the FMP and early postmenopausal years as compared with the late postmenopausal periods. Finally, interleukin-8 levels were lower in years after FMP. Conclusion: The number of years elapsed since the FMP can affect body composition, cardiometabolic risk factors, and inflammatory markers in healthy premenopausal women going through menopausal transition and postmenopausal periods.