Abdominal Obesity, Intra-abdominal Adiposity and Related Cardiometabolic Risk:  Part I Jean-Pierre Després, PhD, FAHA Dire...
Relative Risk of Mortality, Coronary Heart Disease (CHD), and Type 2 Diabetes According to Body Mass Index (BMI) <21.0  2...
Is waist circumference better than body mass index to predict cardiometabolic risk?
Saving and Overconsuming Energy
Obesity: Body Mass Index (BMI) BMI =  Adapted from the World Health Organization. Obesity: Preventing  and Managing the Gl...
The “Heavyweights” of Modifiable Cardiovascular Disease (CVD) Risk Factors Cholesterol Diabetes Smoking Hypertension Globa...
Obesity: An Ill-defined Modifiable Cardiovascular Disease (CVD) Risk Factor Obesity BMI Others ? Cholesterol Diabetes Smok...
Android (Apple) vs. Gynoid (Pear) Obesity A Tribute to a Pioneer Jean Vague (1947) Adapted from Vague J. Presse Med 1947; ...
Obesity as a Risk Factor for Type 2 Diabetes: Importance of Abdominal Fat Accumulation Another Pioneer…the Late III II I I...
Risk of Myocardial Infarction Across Quintiles of BMI and WHR: INTERHEART 4.0 3.0 2.5 2.0 1.5 Odds ratio (95% CI) 1.25 1.0...
Abdominal Obesity and Coronary Heart Disease in Women: The Nurses’ Health Study Low Middle High High (81.8 - <139.7) Middl...
<ul><li>Is total adiposity (body mass index, body fat mass) or subcutaneous fat better than intra-abdominal (visceral) fat...
Intra-abdominal (Visceral) Fat: The Dangerous Inner Fat Intra-abdominal adipose tissue Subcutaneous adipose tissue Front A...
Association Between Fat Mass and Intra-abdominal (Visceral) Adipose Tissue in Men and Premenopausal Women Adapted from Lem...
Intra-abdominal (Visceral) Fat Accumulation in Equally Overweight Men Fat mass:   19.8 kg Intra-abdominal fat :  155 cm 2 ...
Individual Variation in Subcutaneous / Intra-abdominal (Visceral) Fat Accumulation in Obese Women Adapted from Després JP ...
Intra-abdominal (Visceral) Fat Increases the Risk of Type 2 Diabetes in Premenopausal Women Time (min.) Glucose (mmol/l)  ...
Intra-abdominal (Visceral) Fat Increases Cardiovascular Risk in Premenopausal Women HDL cholesterol (mmol/l)   Triglycerid...
Features of the Metabolic Syndrome Commonly Found Among Intra-abdominally (Viscerally) Obese Patients Genetic susceptibili...
The Atherogenic Metabolic Triad of Intra-abdominal (Visceral) Obesity Hyperinsulinemia Small, dense LDL particles Elevated...
Risk of Ischemic Heart Disease (IHD) According to the Cumulative Number of “Traditional” and “Nontraditional” Risk Factors...
The Prevalent Form of the Metabolic Syndrome as Defined by NCEP-ATP III and IDF Pro-inflammatory state Elevated blood pres...
Intra-abdominal (Visceral) Adipose Tissue Area and Waist Girth According to C-Reactive Protein (CRP) Quintiles Intra-abdom...
Inflammation and Cardiovascular Disease: Is Abdominal Obesity the Missing Link?   TNF-  IL-6 Atherogenic, insulin resista...
Potential Contribution of Ectopic Fat Deposition to the Cardiometabolic Risk Profile of Intra-abdominally Obese Patients A...
Intra-abdominal (Visceral) Fat: The Dangerous Inner Fat Intra-abdominal adipose tissue Subcutaneous adipose tissue Front A...
Intra-abdominal (Visceral) Fat is an Independent Predictor of All-cause Mortality in Men Subject A Subject B Subject B  is...
Intra-abdominal (Visceral) Fat is an Independent Predictor of All-cause Mortality in Men * Odds ratios are expressed per s...
The Prevalent Form of the Metabolic Syndrome as Defined by NCEP-ATP III and IDF Pro-inflammatory state Elevated blood pres...
<ul><li>www.cardiometabolic-risk.org </li></ul>
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Abdominal obesity, intra-abdominal adiposity and related cardiometabolic risk: part I

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By Jean-Pierre Després, PhD, FAHA, Scientific Director, International Chair on Cardiometabolic Risk, Professor, Division of Kinesiology, Université Laval, Centre de recherche de l’Institut universitaire de cardiologie et de pneumologie de Québec, Québec, QC, Canada.

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  • Although it is well accepted that obesity is a health hazard and a risk factor for cardiovascular disease and type 2 diabetes, physicians have been perplexed by the remarkable heterogeneity seen among equally obese individuals. Some obese patients have no cardiovascular disease risk factors, whereas others with type 2 diabetes have clinical signs of coronary heart disease and are characterized by insulin resistance, an atherogenic dyslipidemia, and a constellation of risk factors. So while we recognize that obesity is harmful to one’s health, why is this condition so heterogeneous in terms of its clinical manifestations?   One of the reasons why obesity needs to be redefined as a clinical entity is because it has so many faces. Evidence published over the last 25 years has established that the subgroup of overweight or obese patients with an excess of abdominal fat, especially elevated intra-abdominal or visceral adipose tissue, has the highest risk of developing type 2 diabetes and cardiovascular disease. Numerous epidemiological studies over the past few decades have investigated the relationship between body weight and mortality, coronary heart disease (CHD), and diabetes. The Nurses’ Health Study showed the association between body mass index (BMI), as a crude marker of total adiposity, and mortality from all causes, CHD risk, and type 2 diabetes.
  • The objective of this educational program is to review some of the evidence that intra-abdominal (visceral) obesity is a dangerous obesity phenotype that must be assessed and managed in clinical practice. Slide 3 presents the first point to be covered.
  • Before addressing the question of which anthropometric index is most appropriate for use in clinical practice to assess the risks associated with obesity, the reason(s) for the current obesity and type 2 diabetes epidemic require some consideration. “Mother Nature” has engineered humans to be quite efficient from an energy standpoint. Our ancestors had to survive in very difficult environments, in which energy from food was sometimes limited yet the energy requirements of daily life were rather high. While the exponential development of technology has made life quite comfortable, our level of energy expenditure has dropped significantly. Moreover, an increasing number of people consume energy dense food of poor nutritional value. For these simple and rather obvious reasons, an obesity epidemic is sweeping the world, and there is no evidence that this phenomenon will plateau in the near future.
  • When a relative index of weight over height is used, a linear or curvilinear relationship is observed between relative weight and the presence of comorbidities such as type 2 diabetes and cardiovascular disease. The most commonly used index is body mass index (BMI), which is expressed as body weight in kg divided by height in metres squared. When populations are examined, higher BMI values are associated with a greater prevalence of comorbidities. However, in clinical practice, physicians have been perplexed by the fact that equally obese individuals may or may not be characterized by the expected comorbidities of obesity. The reason for this heterogeneity has been for a long time unclear.
  • For a long time obesity was not considered among the “heavyweights” of modifiable cardiovascular disease (CVD) risk factors, which have traditionally included smoking, diabetes, dyslipidemia, and hypertension.
  • Although study of potentially important modifiable cardiovascular disease (CVD) risk factors has been intensive and wide-ranging, obesity has failed to qualify as a well-recognized risk factor.
  • A key factor responsible for obesity’s heterogeneity as a clinical entity is body fat distribution. Professor Jean Vague from the University of Marseille in France was the first to suggest, more than half a century ago, that the complications of obesity were not dependent on excess body fat mass per se but were the consequence of the regional distribution of body fat. Vague coined the term “android” or male-type obesity to characterize the form of overweight and obesity observed among his patients with diabetes or clinical signs of cardiovascular disease. He also proposed that “gynoid” or the lower-body form of obesity frequently found in premenopausal obese women was mostly benign. These remarkable clinical observations did not receive immediate attention from the medical community, and more than 35 years passed before Vague’s hypothesis received further support from “modern” prospective epidemiological studies.
  • The group from the University of Gothenburg led by the late Professor Per Björntorp and Professor Lars Sjöström published results showing the overwhelming association between body fat distribution and the comorbidities of obesity. The Gothenburg Prospective Study presented the incidence of type 2 diabetes in a sample of middle-aged men over a 13.5-year follow-up period. When the men were stratified into tertiles of body mass index (BMI) and waist-to-hip ratio (an index of the proportion of abdominal fat), even among lean individuals (men in the first BMI tertile), the highest waist-to-hip ratio tertile was associated with a 6-fold increase in the risk of developing diabetes (from 0.5% incidence to 2.9%). On the other hand, in the absence of an elevated waist-to-hip ratio, the highest BMI tertile was not associated with an increased risk of developing diabetes. Among equally overweight/obese individuals (the three subgroups of men in the highest BMI tertile), the proportion of abdominal fat (waist-to-hip ratio) had a major impact on the risk of developing diabetes. The risk increased 30-fold among overweight individuals from the lowest to the highest waist-to-hip ratio tertiles. This study published some of the early key evidence for measuring beyond BMI to better appreciate the risk (diabetes in this case) associated with overweight and obesity.
  • More recently, the international case-control INTERHEART study has provided additional robust evidence. Among 27,000 participants stratified on the basis of their body mass index (BMI) values, subjects in the highest quintiles of waist-to-hip ratio (WHR) had an increased odds ratio of myocardial infarction. This case-control study found that the proportion of abdominal fat was much more significant in identifying individuals with clinical signs of coronary heart disease than BMI. However, additional evidence from other prospective studies has indicated that both BMI and WHR (proportion of abdominal fat) or waist circumference (absolute amount of abdominal fat) contribute to the risk of diabetes and cardiovascular disease.
  • This notion is supported by the findings of the Nurses’ Health Study. In this study, women were stratified into tertiles of body mass index (BMI) and tertiles of waist circumference. Irrespective of their BMI tertile, women in the highest waist circumference tertile had an increased risk of coronary heart disease over the 8-year follow-up. The worst-case scenario in the Nurses’ Health Study was to have both high BMI and high waist circumference values. These results provide additional evidence that both BMI and waist circumference are important to assess in clinical practice.
  • Waist circumference adds to the information provided by body mass index. It helps physicians identify the subgroup of overweight/obese patients likely to be characterized by a greater accumulation of abdominal fat. However, an increased waist circumference could be the result of increased accumulation of subcutaneous fat or intra-abdominal (visceral) fat. Evidence suggests that one abdominal fat depot is more important than the other in modulating the risk of diabetes and cardiovascular disease.
  • A cross-sectional image of the abdomen is obtained by computed tomography and usually by scanning the abdomen at the L4–L5 level. Two or three decades ago, computed tomography was a specialized tool found mainly in academic centres. It is now used even in regional hospitals, which makes measuring intra-abdominal (visceral) adiposity fairly easy for the patient and physician. Because of differences in the attenuation values of adipose, muscle, and bone tissue, it is very easy to distinguish fat from muscle and bone on the image. The intra-abdominal, or visceral, adipose tissue appears in white. Studies have indicated that in equally overweight or obese individuals, an excess of intra-abdominal, or visceral, adipose tissue predicts an increased risk of the expected abnormalities of obesity.
  • However, the heavier or more obese a patient is, the more likely he/she is characterized by an increased accumulation of intra-abdominal (visceral) fat. There is a relationship between total body fat mass and intra-abdominal adipose tissue. For any given accumulation of total body fat, men, on average, have twice the amount of intra-abdominal fat than premenopausal women. In addition, since both intra-abdominal adipose tissue and fat mass correlate with each other, correlation analyses are not sufficient to understand the specific contribution of intra-abdominal adipose tissue, subcutaneous adipose tissue, or total adiposity to the cardiometabolic risk profile of patients.
  • One simple approach is to compare individuals with the same amount of total body fat but with low and high levels of intra-abdominal (visceral) adipose tissue. Computed tomography can determine whether there is a high or low accumulation of intra-abdominal adipose tissue in the abdominal scans of two male subjects who have the same age, same body mass index, and same amount of total body fat (fat mass). The intra-abdominal adipose tissue is highlighted in white on the right panels of the slide. The subject in the top panel had a greater accumulation of intra-abdominal fat than the subject in the bottom panel, despite the fact that both men had exactly the same amount of total body fat. The subject in the top panel was therefore at greater risk of diabetes and cardiovascular disease, but this elevated risk would not have been detected even by a very precise measurement of total body fatness.
  • As opposed to the previous slide, which showed computed tomography scans of men, this slide shows abdominal scans of four women characterized by very significant obesity. Despite their significant obesity, it is obvious that the subject in the bottom right panel had little intra-abdominal (visceral) adipose tissue. Accordingly, she had a normal metabolic risk profile. However, the woman in the bottom left panel was characterized by a greater accumulation of intra-abdominal fat and by a disturbed metabolic risk profile. Therefore, the woman in the bottom left panel of this slide was at greater risk of diabetes and cardiovascular disease, but this elevated risk would not have been detected even by a very precise measurement of total body fatness.
  • These two graphs show the plasma glucose and insulin responses to a 75 g oral glucose load among three groups of women: lean controls (green), obese women with low levels of intra-abdominal (visceral) fat (yellow), and obese women (same level of obesity as the other obese group) with high levels of intra-abdominal fat (red). Trivial differences in glucose tolerance and insulin response were observed between the lean controls and the obese women with little intra-abdominal fat. However, the intra-abdominally obese women had a greater glycemic response in the presence of marked hyperinsulinemia, suggesting a greater level of insulin resistance in subjects with high levels of intra-abdominal adipose tissue compared to equally obese women with low levels of intra-abdominal fat. Thus, intra-abdominally obese patients form a subgroup that is at much greater risk of developing type 2 diabetes.
  • When two simple indices of the lipid profile were examined in the same three groups of women, only the intra-abdominally obese women were characterized by marked hypertriglyceridemia and by reduced HDL cholesterol levels. Intra-abdominal obesity is associated with insulin resistance and with the high triglyceride/low HDL cholesterol dyslipidemic state. Similar results have been reported in men.
  • Additional metabolic studies conducted around the world have shown that among equally obese patients, subjects with an excess of intra-abdominal (visceral) adipose tissue have the worst metabolic risk profile. These subjects show insulin resistance and compensatory hyperinsulinemia as a sign of insulin resistance. Among genetically susceptible individuals, insulin resistance favours the development of glucose intolerance and eventually leads to type 2 diabetes when the insulin resistant state is accompanied by a relative deficit in insulin secretion. However, even in the absence of glucose intolerance and marked hyperglycemia, the presence of intra-abdominal obesity and insulin resistance have been associated with a very typical dyslipidemic profile that includes hypertriglyceridemia, low HDL cholesterol concentration, elevated apolipoprotein B as a marker of an increased concentration of atherogenic lipoproteins, and an increased concentration of small, dense LDL particles. In addition to the dyslipidemic insulin resistant profile of intra-abdominally obese patients, these individuals are characterized by impaired fibrinolysis, an increased susceptibility to thrombosis, endothelial dysfunction (as an early sign of endothelial damage), and an inflammatory profile.
  • The risk associated with some of the features of intra-abdominal (visceral) obesity has not been examined in many prospective studies because markers of insulin resistance and related abnormalities have not been commonly measured. The Québec Cardiovascular Study, a prospective study conducted in a sample of initially asymptomatic middle-aged men, provided an opportunity to test the hypothesis that fasting hyperinsulinemia, as a basic marker of insulin resistance, could be a relevant marker of coronary heart disease risk. Furthermore, since hyperinsulinemic men are often characterized by elevated apolipoprotein B (apo B) and small LDL particles, the study tested the hypothesis that this atherogenic metabolic triad of abnormalities, which is commonly found in intra-abdominally obese individuals, could increase the risk of coronary heart disease.
  • The Québec Cardiovascular Study demonstrated the 5-year risk of ischemic heart disease (IHD) based on the number of features of the atherogenic metabolic triad often found in patients with intra-abdominal (visceral) obesity. Men who had none of the features of the metabolic triad at baseline were considered as the reference group to whom an IHD odds ratio (OR) of 1.0 was attributed. Men characterized by the 3 previously mentioned abnormalities (atherogenic metabolic triad) had a substantially increased risk of IHD (20.8-fold increase in IHD risk). Adjusting this OR for traditional risk factors and lipid variables such as LDL cholesterol, triglycerides, and HDL cholesterol failed to substantially alter the OR associated with the presence of hyperinsulinemia, elevated apolipoprotein B, and small, dense LDL particles. The ratio remained elevated 18-fold among men with the atherogenic metabolic triad compared to men with none of those abnormalities. In comparison, the presence of the traditional lipid triad (elevated triglycerides, elevated LDL cholesterol, and reduced HDL cholesterol) increased IHD risk 4.4-fold. These results from the Québec Cardiovascular Study provide evidence that more refined markers of the metabolic consequences of intra-abdominal obesity could improve our ability to assess coronary heart disease risk beyond traditional risk factors and lipid variables. Further work is clearly warranted to examine this question.
  • The complications of intra-abdominal (visceral) adiposity appear to increase the risk of coronary heart disease beyond what could be predicted by the presence of traditional risk factors. As an atherogenic dyslipidemia and insulin resistance are conditions frequently observed in clinical practice among patients with abdominal obesity and excess intra-abdominal adipose tissue accumulation, it has been suggested that the most prevalent form of the metabolic syndrome is found among patients with an elevated waistline and an excess of intra-abdominal adipose tissue. In addition to these complications, inflammation has also been examined in the context of abdominal obesity, and studies have shown that it is associated with abdominal fat accumulation.
  • The intra-abdominal adipose tissue accumulation and the waist circumference values were recorded across quintiles of C-reactive protein concentration (CRP) in a sample of middle-age men. High CRP concentrations were associated with an elevated waist circumference and a greater accumulation of intra-abdominal adipose tissue. Multivariate analyses conducted in this study revealed that waist circumference was the best predictor of individual differences in CRP concentration.
  • This close relationship between the expanded waistline and elevated C-reactive protein (CRP) levels could be due to macrophage infiltration of the adipose tissue of abdominally obese patients. These macrophages can produce inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), which can have a local impact on adipose tissue metabolism as well as systemic effects. This can exacerbate the dysmetabolic profile noted among patients with an excess of intra-abdominal adipose tissue. For instance, the TNF-α could make adipose tissue insulin resistant, and it also has an inhibitory effect on the production of adiponectin (an important adipose tissue-derived cytokine that has been suggested to have anti-atherogenic and anti-diabetic properties). In addition, the release of IL-6 by fat cells is known to stimulate the production of CRP through the liver.
  • Although the “portal free fatty acid hypothesis” has been suggested to explain some of the metabolic abnormalities associated with excess adipose tissue accumulation, the hyperlipolytic state of the expanded intra-abdominal (visceral) depot cannot, by itself, explain all of the metabolic abnormalities observed in intra-abdominally obese patients. However, taking into account the exciting new findings indicating that adipose tissue is an important endocrine organ and a site of production for inflammatory cytokines [such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α)] and a potentially protective cytokine (such as adiponectin, which is reduced in intra-abdominal obesity), the comprehensive alterations in the metabolic profile observed in intra-abdominally obese patients can now be reconciled. Therefore, the hyperlipolytic state and pro-inflammatory profile of intra-abdominal obesity could explain the constellation of metabolic abnormalities found in intra-abdominally obese patients.
  • We now have evidence that the intra-abdominal or visceral fat depot is clearly a very significant correlate of metabolic abnormalities observed in overweight and obese patients.
  • Recently, Professor Robert Ross and colleagues from Queen’s University in Kingston, Ontario, Canada, have provided evidence that increased intra-abdominal (visceral) adipose tissue accumulation increases mortality risk.
  • In this study, proper adjustment of the mortality odds ratio associated with intra-abdominal (visceral) fat (1.8) for concomitant variation in subcutaneous fat, waist circumference, or an estimate of liver fat infiltration (CTL/CTS ratio) failed to reduce the odds ratio associated with excess intra-abdominal fat accumulation (as shown in the right panel of the figure).
  • The complications of intra-abdominal (visceral) adiposity appear to increase the risk of coronary heart disease beyond what could be predicted by the presence of traditional risk factors. Since atherogenic dyslipidemia and insulin resistance are conditions frequently observed in clinical practice among patients with abdominal obesity and excess intra-abdominal adipose tissue accumulation, it has been suggested that the most prevalent form of the metabolic syndrome is found among patients with an elevated waistline and an excess of intra-abdominal adipose tissue. Inflammation in the context of abdominal obesity has also been examined, and studies have shown that it is associated with abdominal fat accumulation. The critical role played by the abdominal obesity associated with an excess of intra-abdominal fat justifies the recommendations of the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III) and the recent guidelines of the International Diabetes Federation (IDF). Both organizations have recognized abdominal obesity as the most prevalent form of the metabolic syndrome and both have recommended measuring waist circumference over body mass index to estimate the amount of abdominal fat.
  • Abdominal obesity, intra-abdominal adiposity and related cardiometabolic risk: part I

    1. 1. Abdominal Obesity, Intra-abdominal Adiposity and Related Cardiometabolic Risk: Part I Jean-Pierre Després, PhD, FAHA Director of Research, Cardiology Centre de recherche de l’Institut universitaire de cardiologie et de pneumologie de Québec Scientific Director, International Chair on Cardiometabolic Risk Québec, Canada
    2. 2. Relative Risk of Mortality, Coronary Heart Disease (CHD), and Type 2 Diabetes According to Body Mass Index (BMI) <21.0  29.0 BMI (kg/m 2 ) <22.0  35.0 BMI (kg/m 2 ) <19.0  32.0 BMI (kg/m 2 ) Adapted from Manson JE et al. N Engl J Med 1995; 333: 677–85 | Willett WC et al. JAMA 1995; 273: 461–5 | Colditz GA et al. Ann Intern Med 1995; 122: 481-6 Relative risk of: 2.0 1.5 1.0 0.5 0.0 4.0 3.0 2.0 1.0 0.0 8.0 6.0 4.0 2.0 0.0 Mortality CHD Diabetes
    3. 3. Is waist circumference better than body mass index to predict cardiometabolic risk?
    4. 4. Saving and Overconsuming Energy
    5. 5. Obesity: Body Mass Index (BMI) BMI = Adapted from the World Health Organization. Obesity: Preventing and Managing the Global Epidemic. Geneva: WHO, 2000 Weight (kg) Height (m 2 ) BMI (kg/m 2 ) Risk of Comorbidities Healthy weight 18.5 – 24.9 Normal Overweight 25.0 – 29.9 Increased Obese Class I 30.0 – 34.9 High Obese Class II 35.0 – 39.9 Very High Obese Class III > 40.0 Extremely High
    6. 6. The “Heavyweights” of Modifiable Cardiovascular Disease (CVD) Risk Factors Cholesterol Diabetes Smoking Hypertension Global CVD Risk LDL HDL
    7. 7. Obesity: An Ill-defined Modifiable Cardiovascular Disease (CVD) Risk Factor Obesity BMI Others ? Cholesterol Diabetes Smoking Hypertension LDL HDL Global CVD Risk BMI: body mass index
    8. 8. Android (Apple) vs. Gynoid (Pear) Obesity A Tribute to a Pioneer Jean Vague (1947) Adapted from Vague J. Presse Med 1947; 30: 339–40
    9. 9. Obesity as a Risk Factor for Type 2 Diabetes: Importance of Abdominal Fat Accumulation Another Pioneer…the Late III II I I II III 13.5-year incidence of type 2 diabetes (%) (Overweight) (Lean) Body mass index tertiles Waist-to-hip ratio tertiles Per Björntorp Adapted from Ohlson LO et al. Diabetes 1985; 34: 1055-8
    10. 10. Risk of Myocardial Infarction Across Quintiles of BMI and WHR: INTERHEART 4.0 3.0 2.5 2.0 1.5 Odds ratio (95% CI) 1.25 1.0 0.9 0.8 <20 20–23 23.1–25 25.1–27 27.1–29 >30 BMI (kg/m 2 ) Adapted from Yusuf S et al. Lancet 2005; 366: 1640-9 Copyright 2005, with permission from Elsevier BMI: body mass index WHR: waist-to-hip ratio 3.5
    11. 11. Abdominal Obesity and Coronary Heart Disease in Women: The Nurses’ Health Study Low Middle High High (81.8 - <139.7) Middle (73.7 - <81.8) Low (38.1 - <73.7) (25.2 - <48.8) (22.2 - <25.2) (12.2 - <22.2) Waist girth tertiles (cm) Incidence rate per 100,000 person-years Body mass index tertiles (kg/m 2 ) Adapted from Rexrode KM et al. JAMA 1998; 280: 1843-8 Follow-up of 8 years 140 120 100 80 60 40 20 0
    12. 12. <ul><li>Is total adiposity (body mass index, body fat mass) or subcutaneous fat better than intra-abdominal (visceral) fat to predict cardiometabolic risk? </li></ul>
    13. 13. Intra-abdominal (Visceral) Fat: The Dangerous Inner Fat Intra-abdominal adipose tissue Subcutaneous adipose tissue Front Adapted from Lemieux I et al. Ann Endocrinol 2001; 62: 255-61 Back
    14. 14. Association Between Fat Mass and Intra-abdominal (Visceral) Adipose Tissue in Men and Premenopausal Women Adapted from Lemieux S et al. Am J Clin Nutr 1993; 58: 463-7 Intra-abdominal adipose tissue (cm 2 ) 0 10 20 30 40 50 60 70 Fat mass (kg) 300 250 200 150 100 50 0 Women: r=0.85 Men: r=0.69
    15. 15. Intra-abdominal (Visceral) Fat Accumulation in Equally Overweight Men Fat mass: 19.8 kg Intra-abdominal fat : 155 cm 2 Fat mass: 19.8 kg Intra-abdominal fat : 96 cm 2 Adapted from Després JP et al. In: AF Roche, SB Heymsfield, TG Lohman (eds.), Human Body Composition, Human Kinetics,149-66,1996
    16. 16. Individual Variation in Subcutaneous / Intra-abdominal (Visceral) Fat Accumulation in Obese Women Adapted from Després JP Nutrition 1993; 9: 452-9
    17. 17. Intra-abdominal (Visceral) Fat Increases the Risk of Type 2 Diabetes in Premenopausal Women Time (min.) Glucose (mmol/l) 0 1,2 1,2 1,2 1,2 1,2 1,2 1 30 60 90 120 150 180 10.0 9.0 8.0 7.0 6.0 5.0 4.0 Nonobese controls (1) Obese low intra-abdominal fat (2) Obese high intra-abdominal fat 1000 800 600 400 200 0 Time (min.) 0 30 60 90 120 150 180 Insulin (pmol/l) 1,2 1 1,2 1,2 1,2 1 1 1 1 1 1 From Després JP. In: H Rifkin, JA Colwell, SI Taylor (eds.), Diabetes 1991, Elsevier Science Publishers BV Amsterdam, The Netherlands, 95-9, 1991 Reproduced with permission 1,2: significantly different from the corresponding subgroups 1 1
    18. 18. Intra-abdominal (Visceral) Fat Increases Cardiovascular Risk in Premenopausal Women HDL cholesterol (mmol/l) Triglycerides (mmol/l) 1,2 1 Adapted from Després JP et al. Arteriosclerosis 1990; 10: 497-511 1,2 1.5 1.4 1.3 1.2 1.1 1.0 0.9 0.8 3.0 2.5 2.0 1.5 1.0 0.5 0.0 1,2: significantly different from the corresponding subgroup Nonobese controls (1) Obese low intra-abdominal fat (2) Obese high intra-abdominal fat
    19. 19. Features of the Metabolic Syndrome Commonly Found Among Intra-abdominally (Viscerally) Obese Patients Genetic susceptibility to hypertension, type 2 diabetes, and coronary heart disease ultimately affects the clinical features of the metabolic syndrome Adapted from Lemieux I and Després JP. In: PG Kopelman (ed.), Management of Obesity and Related Disorders, Martin Dunitz, 45-63, 2001 <ul><li>Hypertriglyceridemia </li></ul><ul><li>Insulin resistance </li></ul><ul><li>Low HDL cholesterol </li></ul><ul><li>Hyperinsulinemia </li></ul><ul><li>Elevated apolipoprotein B </li></ul><ul><li>Glucose intolerance </li></ul><ul><li>Small, dense LDL particles </li></ul><ul><li>Impaired fibrinolysis </li></ul><ul><li>Inflammatory profile </li></ul><ul><li>Endothelial dysfunction </li></ul>
    20. 20. The Atherogenic Metabolic Triad of Intra-abdominal (Visceral) Obesity Hyperinsulinemia Small, dense LDL particles Elevated apo B concentrations Beyond LDL cholesterol, blood pressure, type 2 diabetes… The atherogenic metabolic triad
    21. 21. Risk of Ischemic Heart Disease (IHD) According to the Cumulative Number of “Traditional” and “Nontraditional” Risk Factors: The Québec Cardiovascular Study Adapted from Lamarche B et al. JAMA 1998; 279: 1955-61 Odds ratio* * Odds ratios are adjusted for systolic blood pressure, family history of IHD, and medication use 25 20 15 10 5 0 0 1 2 3 1.0 1.0 1.8 4.7 2.8 9.1 (p=0.01) 4.4 (p=0.01) 20.8 (p<0.001) Traditional risk factors: LDL cholesterol, triglycerides and HDL cholesterol Nontraditional risk factors: Insulin, apolipoprotein B and small, dense LDL particles
    22. 22. The Prevalent Form of the Metabolic Syndrome as Defined by NCEP-ATP III and IDF Pro-inflammatory state Elevated blood pressure Insulin resistance Atherogenic dyslipidemia NCEP-ATP III: National Cholesterol Education Program – Adult Treatment Panel III IDF: International Diabetes Federation Abdominal obesity Pro-thrombotic state
    23. 23. Intra-abdominal (Visceral) Adipose Tissue Area and Waist Girth According to C-Reactive Protein (CRP) Quintiles Intra-abdominal adipose tissue (cm 2 ) CRP quintiles 1 1 1 1,3 Waist circumference (cm) CRP quintiles 1 1 1,2 1,2,3 Adapted from Lemieux I et al. Arterioscler Thromb Vasc Biol 2001; 21: 961-7 Legend: 1,2,3: significantly different from the corresponding quintiles (1) (2) (3) (4) (5) (1) (2) (3) (4) (5)
    24. 24. Inflammation and Cardiovascular Disease: Is Abdominal Obesity the Missing Link? TNF-  IL-6 Atherogenic, insulin resistant “dysmetabolic milieu”  CRP ? ?  Risk of acute coronary syndrome ? Adipose tissue Adapted from Després JP Int J Obes 2003; 27: S22-4 Reproduced with permission CRP: C-reactive protein IL-6: interleukin-6 TNF-  : tumor necrosis factor- 
    25. 25. Potential Contribution of Ectopic Fat Deposition to the Cardiometabolic Risk Profile of Intra-abdominally Obese Patients Altered cardiometabolic risk profile  Systemic free fatty acids Coronary atherosclerosis unstable plaque  Intra-abdominal (visceral) adipose tissue  Lipoprotein lipase Insulin resistance  Hepatic lipase Lipid deposition Insulin-resistant subcutaneous adipose tissue ?  Portal free fatty acids  Insulin  Glucose  Triglycerides  Apolipoprotein B Adapted from Després JP. Ann Med 2006; 38: 52-63 Reproduced with permission  Plasminogen activator inhibitor-1  Interleukin-6  Tumor necrosis factor-   Adiponectin Skeletal muscle Liver
    26. 26. Intra-abdominal (Visceral) Fat: The Dangerous Inner Fat Intra-abdominal adipose tissue Subcutaneous adipose tissue Front Adapted from Lemieux I et al. Ann Endocrinol 2001; 62: 255-61 Back
    27. 27. Intra-abdominal (Visceral) Fat is an Independent Predictor of All-cause Mortality in Men Subject A Subject B Subject B is at a 2-fold higher risk for mortality Risk of death Intra-abdominal fat (kg) Intra-abdominal fat is shown in red Adapted from Kuk JL et al. Obesity 2006; 14: 336-41 0 0.5 1.0 1.5
    28. 28. Intra-abdominal (Visceral) Fat is an Independent Predictor of All-cause Mortality in Men * Odds ratios are expressed per standard deviation for each variable Adapted from Kuk JL et al. Obesity 2006; 14: 336-41 Odds ratios for mortality* MODEL 1 1.8 1.4 1.4 0.8 1.8 1.0 0.6 1.3 MODEL 2 Control for age + follow-up time Control for age, follow-up time, abdominal subcutaneous fat, intra-abdominal fat, and liver fat 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 Odds ratios for mortality* Subcutaneous fat CTL / CTS (index of liver fat) Intra-abdominal fat Waist circumference
    29. 29. The Prevalent Form of the Metabolic Syndrome as Defined by NCEP-ATP III and IDF Pro-inflammatory state Elevated blood pressure Insulin resistance Atherogenic dyslipidemia NCEP-ATP III: National Cholesterol Education Program – Adult Treatment Panel III IDF: International Diabetes Federation Abdominal obesity Pro-thrombotic state
    30. 30. <ul><li>www.cardiometabolic-risk.org </li></ul>
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