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Journal ArticleDOI

Impact of Abdominal Visceral and Subcutaneous Adipose Tissue on Cardiometabolic Risk Factors: The Jackson Heart Study

TL;DR: The results from this study suggest that relations with cardiometabolic risk factors are consistent with a pathogenic role of abdominal adiposity in participants of African ancestry.
Abstract: Objective: Obesity is a major driver of cardiometabolic risk. Abdominal visceral adipose tissue (VAT) and sc adipose tissue (SAT) may confer differential metabolic risk profiles. We investigated the relations of VAT and SAT with cardiometabolic risk factors in the Jackson Heart Study cohort. Methods: Participants from the Jackson Heart Study (n = 2477; 64% women; mean age, 58 yr) underwent multidetector computed tomography, and the volumetric amounts of VAT and SAT were assessed between 2007 and 2009. Cardiometabolic risk factors were examined by sex in relation to VAT and SAT. Results: Men had a higher mean volume of VAT (873 vs. 793 cm3) and a lower mean volume of SAT (1730 vs. 2659 cm3) than women (P = 0.0001). Per 1-sd increment in either VAT or SAT, we observed elevated levels of fasting plasma glucose and triglyceride, lower levels of high-density lipoprotein-cholesterol, and increased odds ratios for hypertension, diabetes, and metabolic syndrome. The effect size of VAT in women was larger than tha...
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Journal ArticleDOI
TL;DR: In clinical practice, measuring waist circumference in addition to the body mass index could be helpful for the identification and management of a subgroup of overweight or obese patients at high cardiometabolic risk.
Abstract: Excess intra-abdominal adipose tissue accumulation, often termed visceral obesity, is part of a phenotype including dysfunctional subcutaneous adipose tissue expansion and ectopic triglyceride storage closely related to clustering cardiometabolic risk factors. Hypertriglyceridemia; increased free fatty acid availability; adipose tissue release of proinflammatory cytokines; liver insulin resistance and inflammation; increased liver VLDL synthesis and secretion; reduced clearance of triglyceride-rich lipoproteins; presence of small, dense LDL particles; and reduced HDL cholesterol levels are among the many metabolic alterations closely related to this condition. Age, gender, genetics, and ethnicity are broad etiological factors contributing to variation in visceral adipose tissue accumulation. Specific mechanisms responsible for proportionally increased visceral fat storage when facing positive energy balance and weight gain may involve sex hormones, local cortisol production in abdominal adipose tissues, endocannabinoids, growth hormone, and dietary fructose. Physiological characteristics of abdominal adipose tissues such as adipocyte size and number, lipolytic responsiveness, lipid storage capacity, and inflammatory cytokine production are significant correlates and even possible determinants of the increased cardiometabolic risk associated with visceral obesity. Thiazolidinediones, estrogen replacement in postmenopausal women, and testosterone replacement in androgen-deficient men have been shown to favorably modulate body fat distribution and cardiometabolic risk to various degrees. However, some of these therapies must now be considered in the context of their serious side effects. Lifestyle interventions leading to weight loss generally induce preferential mobilization of visceral fat. In clinical practice, measuring waist circumference in addition to the body mass index could be helpful for the identification and management of a subgroup of overweight or obese patients at high cardiometabolic risk.

1,970 citations

Journal ArticleDOI
TL;DR: It has been proposed that medical progress at tackling CVD could be offset, at least to a certain extent, by the dramatic consequences of the authors' toxic lifestyle, which includes poor nutrition or excess caloric consumption and a sedentary lifestyle, both leading to obesity and type 2 diabetes mellitus.
Abstract: Epidemiological, clinical, and mechanistic preclinical studies conducted in the field of cardiovascular medicine have led to remarkable progress in our understanding of nonmodifiable and modifiable risk factors for cardiovascular disease (CVD). For instance, although the prevalence of CVD had reached devastating levels in the 1950s, proper focus on the major CVD risk factors first identified at the time, such as smoking, hypertension, and high cholesterol levels, has allowed these risk factors to be targeted both at the clinical level and through public health policies.1 As a consequence, coronary heart disease mortality has decreased by ≈50% over the past 50 years.2 Ford et al2 have suggested that better screening and medical management of these CVD risk factors and the medical procedures developed to treat the various acute manifestations of CVD have had a favorable impact on its related mortality rates. However, the current overconsumption of processed and energy-dense food products of poor nutritional value combined with our sedentary lifestyle have contributed to the emergence of new drivers of CVD risk: obesity and type 2 diabetes mellitus (Figure 1).3,4 It has been proposed that our medical progress at tackling CVD could be offset, at least to a certain extent, by the dramatic consequences of our toxic lifestyle, which includes poor nutrition or excess caloric consumption and a sedentary lifestyle, both leading to obesity and type 2 diabetes mellitus.2 Figure 1. Some of the alterations in the metabolic risk profile that have been found to be related to abdominal obesity assessed by anthropometry and later to excess visceral adiposity/ectopic fat assessed by imaging techniques. This constellation of metabolic abnormalities increases the risk of type 2 diabetes mellitus and of various cardiovascular outcomes. CVD indicates cardiovascular disease; HDL, high-density lipoprotein; LDL, low-density lipoprotein. Thus, the mosaic of modifiable …

984 citations

Journal ArticleDOI
TL;DR: The evidence reviewed in this paper suggests that adipose tissue quality/function is as important, if not more so, than its amount in determining the overall health and CV risks of overweight/obesity.

919 citations

Journal ArticleDOI
19 Sep 2012-JAMA
TL;DR: Excess visceral fat and insulin resistance, but not general adiposity, were independently associated with incident prediabetes and type 2 diabetes mellitus in obese adults in a multiethnic, population-based cohort of obese adults.
Abstract: Context The risk of type 2 diabetes mellitus is heterogeneous among obese individuals. Factors that discriminate prediabetes or diabetes risk within this population have not been well characterized. A dysfunctional adiposity phenotype, characterized by excess visceral fat and insulin resistance, may contribute to diabetes development in those with obesity. Objective To investigate associations between adiposity phenotypes and risk for incident prediabetes and diabetes in a multiethnic, population-based cohort of obese adults. Design, Setting, and Participants Among 732 obese participants (body mass index ≥30) aged 30 to 65 years without diabetes or cardiovascular disease enrolled between 2000 and 2002 in the Dallas Heart Study, we measured body composition by dual energy x-ray absorptiometry and magnetic resonance imaging (MRI); circulating adipokines and biomarkers of insulin resistance, dyslipidemia, and inflammation; and subclinical atherosclerosis and cardiac structure and function by computed tomography and MRI. Main Outcome Measures Incidence of diabetes through a median 7.0 years (interquartile range, 6.6-7.6) of follow-up. In a subgroup of 512 participants with normal fasting glucose values at baseline, incidence of the composite of prediabetes or diabetes was determined. Results Of the 732 participants (mean age, 43 years; 65% women; 71% nonwhite), 84 (11.5%) developed diabetes. In multivariable analysis, higher baseline visceral fat mass (odds ratio [OR] per 1 SD [1.4 kg], 2.4; 95% CI, 1.6-3.7), fructosamine level (OR per 1 SD [1.1 μmol/L], 2.0; 95% CI, 1.4-2.7), fasting glucose level (OR per 1 SD [1.1 μmol/L], 1.9; 95% CI, 1.4-2.6), family history of diabetes (OR, 2.3; 95% CI, 1.3-4.3), systolic blood pressure (OR per 10 mm Hg, 1.3; 95% CI, 1.1-1.5), and weight gain over follow-up (OR per 1 kg, 1.06; 95% CI, 1.02-1.10) were independently associated with diabetes, with no associations observed for body mass index, total body fat, or abdominal subcutaneous fat. Among the 512 participants with normal baseline glucose values, the composite outcome of prediabetes or diabetes occurred in 39.1% and was independently associated with baseline measurements of visceral fat mass; levels of fasting glucose, insulin, and fructosamine; older age; nonwhite race; family history of diabetes; and weight gain over follow-up (P Conclusion Excess visceral fat and insulin resistance, but not general adiposity, were independently associated with incident prediabetes and type 2 diabetes mellitus in obese adults.

532 citations

Journal ArticleDOI
TL;DR: It is proposed that obesity can no longer be evaluated solely by the body mass index (expressed in kg/m2) because it represents a heterogeneous entity and should be referred to obesities rather than obesity.
Abstract: This review addresses the interplay between obesity, type 2 diabetes mellitus, and cardiovascular diseases. It is proposed that obesity, generally defined by an excess of body fat causing prejudice to health, can no longer be evaluated solely by the body mass index (expressed in kg/m2) because it represents a heterogeneous entity. For instance, several cardiometabolic imaging studies have shown that some individuals who have a normal weight or who are overweight are at high risk if they have an excess of visceral adipose tissue-a condition often accompanied by accumulation of fat in normally lean tissues (ectopic fat deposition in liver, heart, skeletal muscle, etc). On the other hand, individuals who are overweight or obese can nevertheless be at much lower risk than expected when faced with excess energy intake if they have the ability to expand their subcutaneous adipose tissue mass, particularly in the gluteal-femoral area. Hence, excessive amounts of visceral adipose tissue and of ectopic fat largely define the cardiovascular disease risk of overweight and moderate obesity. There is also a rapidly expanding subgroup of patients characterized by a high accumulation of body fat (severe obesity). Severe obesity is characterized by specific additional cardiovascular health issues that should receive attention. Because of the difficulties of normalizing body fat content in patients with severe obesity, more aggressive treatments have been studied in this subgroup of individuals such as obesity surgery, also referred to as metabolic surgery. On the basis of the above, we propose that we should refer to obesities rather than obesity.

496 citations

References
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Journal ArticleDOI
TL;DR: Although ATP III identified CVD as the primary clinical outcome of the metabolic syndrome, most people with this syndrome have insulin resistance, which confers increased risk for type 2 diabetes, when diabetes becomes clinically apparent, CVD risk rises sharply.
Abstract: The National Cholesterol Education Program’s Adult Treatment Panel III report (ATP III)1 identified the metabolic syndrome as a multiplex risk factor for cardiovascular disease (CVD) that is deserving of more clinical attention. The cardiovascular community has responded with heightened awareness and interest. ATP III criteria for metabolic syndrome differ somewhat from those of other organizations. Consequently, the National Heart, Lung, and Blood Institute, in collaboration with the American Heart Association, convened a conference to examine scientific issues related to definition of the metabolic syndrome. The scientific evidence related to definition was reviewed and considered from several perspectives: (1) major clinical outcomes, (2) metabolic components, (3) pathogenesis, (4) clinical criteria for diagnosis, (5) risk for clinical outcomes, and (6) therapeutic interventions. ATP III viewed CVD as the primary clinical outcome of metabolic syndrome. Most individuals who develop CVD have multiple risk factors. In 1988, Reaven2 noted that several risk factors (eg, dyslipidemia, hypertension, hyperglycemia) commonly cluster together. This clustering he called Syndrome X , and he recognized it as a multiplex risk factor for CVD. Reaven and subsequently others postulated that insulin resistance underlies Syndrome X (hence the commonly used term insulin resistance syndrome ). Other researchers use the term metabolic syndrome for this clustering of metabolic risk factors. ATP III used this alternative term. It avoids the implication that insulin resistance is the primary or only cause of associated risk factors. Although ATP III identified CVD as the primary clinical outcome of the metabolic syndrome, most people with this syndrome have insulin resistance, which confers increased risk for type 2 diabetes. When diabetes becomes clinically apparent, CVD risk rises sharply. Beyond CVD and type 2 diabetes, individuals with metabolic syndrome seemingly are susceptible to other conditions, notably polycystic ovary syndrome, fatty liver, cholesterol gallstones, asthma, sleep disturbances, and some …

6,238 citations


"Impact of Abdominal Visceral and Su..." refers methods in this paper

  • ...Obesity was defined by a BMI of at least 30 kg/m(2), and modified NationalCholesterolEducationProgramAdultTreatmentPanel III criteria were used to define the metabolic syndrome (17)....

    [...]

Journal ArticleDOI
TL;DR: These findings are consistent with the hypothesized role of visceral fat as a unique, pathogenic fat depot and Measurement of VAT may provide a more complete understanding of metabolic risk associated with variation in fat distribution.
Abstract: Background— Visceral adipose tissue (VAT) compartments may confer increased metabolic risk. The incremental utility of measuring both visceral and subcutaneous abdominal adipose tissue (SAT) in association with metabolic risk factors and underlying heritability has not been well described in a population-based setting. Methods and Results— Participants (n=3001) were drawn from the Framingham Heart Study (48% women; mean age, 50 years), were free of clinical cardiovascular disease, and underwent multidetector computed tomography assessment of SAT and VAT volumes between 2002 and 2005. Metabolic risk factors were examined in relation to increments of SAT and VAT after multivariable adjustment. Heritability was calculated using variance-components analysis. Among both women and men, SAT and VAT were significantly associated with blood pressure, fasting plasma glucose, triglycerides, and high-density lipoprotein cholesterol and with increased odds of hypertension, impaired fasting glucose, diabetes mellitus, ...

2,501 citations


"Impact of Abdominal Visceral and Su..." refers background in this paper

  • ...Women are generally characterized by a greater body fat content and preferential accumulation of adipose tissue in the gluteofemoral region, whereas men are prone to abdominal fat deposition, particularly in the abdominal cavity, a condition that has been described as visceral obesity (3, 6, 26)....

    [...]

  • ...also be a health risk because it has been associated with cardiometabolic risk factors and insulin resistance (3, 4)....

    [...]

  • ...and SAT with cardiometabolic risk (3, 14, 19, 20)....

    [...]

  • ...metabolic risk factors after accounting for BMI (3, 18),...

    [...]

  • ...In the Framingham Heart Study, larger volumes of SAT were associated with more adverse risk factor profiles (3), although increasing SAT was associated with lower triglyceride levels only when examined within narrow ranges of VAT (18)....

    [...]

Journal ArticleDOI
TL;DR: Although both IL-6 and TNF alpha are expressed by adipose tissue, the results show that there are important differences in their systemic release.
Abstract: We measured arterio-venous differences in concentrations of tumor necrosis factor-alpha (TNF alpha) and interleukin-6 (IL-6) across a sc adipose tissue bed in the postabsorptive state in 39 subjects [22 women and 17 men; median age, 36 yr (interquartile range, 26-48 yr); body mass index, 31.8 kg/m2 (range, 22.3- 38.7 kg/m2); percent body fat, 28.7% (range, 17.6-50.7%)]. A subgroup of 8 subjects had arteriovenous differences measured across forearm muscle. Thirty subjects were studied from late morning to early evening; 19 ate a high carbohydrate meal around 1300 h, and 11 continued to fast. We found a greater than 2-fold increase in IL-6 concentrations across the adipose tissue bed [arterial, 2.27 pg/mL (range, 1.42-3.53 pg/mL); venous, 6.71 pg/mL (range, 3.36-9.62 pg/mL); P < 0.001], but not across forearm muscle. Arterial plasma concentrations of IL-6 correlated significantly with body mass index (Spearman's r = 0.48; P < 0.01) and percent body fat (Spearman's r = 0.49; P < 0.01). Subcutaneous adipose tissue IL-6 production increased by the early evening (1800-1900 h) in both subjects who had extended their fasting and those who had eaten. Neither deep forearm nor sc adipose tissue consistently released TNF alpha [across adipose tissue: arterial, 1.83 pg/mL (range, 1.36-2.34 pg/mL); venous, 1.85 pg/mL (range, 1.44-2.53 pg/mL); P = NS: across forearm muscle: arterial, 1.22 pg/mL (range, 0.74-2.76 pg/mL); venous, 0.99 pg/mL (range, 0.69-1.70 pg/mL); P = NS]. Although both IL-6 and TNF alpha are expressed by adipose tissue, our results show that there are important differences in their systemic release. TNF alpha is not released by this sc depot. In contrast, IL-6 is released from the depot and is thereby able to signal systemically.

2,169 citations


"Impact of Abdominal Visceral and Su..." refers background in this paper

  • ...SAT may preferentially release more leptin and IL-6, whereas VAT may mainly release TNF- (28)....

    [...]

Journal ArticleDOI
TL;DR: Although ATP III identified CVD as the primary clinical outcome of the metabolic syndrome, most people with this syndrome have insulin resistance, which confers increased risk for type 2 diabetes, when diabetes becomes clinically apparent, CVD risk rises sharply.
Abstract: The National Cholesterol Education Program’s Adult Treatment Panel III report (ATP III)1 identified the metabolic syndrome as a multiplex risk factor for cardiovascular disease (CVD) that is deserving of more clinical attention. The cardiovascular community has responded with heightened awareness and interest. ATP III criteria for metabolic syndrome differ somewhat from those of other organizations. Consequently, the National Heart, Lung, and Blood Institute, in collaboration with the American Heart Association, convened a conference to examine scientific issues related to definition of the metabolic syndrome. The scientific evidence related to definition was reviewed and considered from several perspectives: (1) major clinical outcomes, (2) metabolic components, (3) pathogenesis, (4) clinical criteria for diagnosis, (5) risk for clinical outcomes, and (6) therapeutic interventions. ATP III viewed CVD as the primary clinical outcome of metabolic syndrome. Most individuals who develop CVD have multiple risk factors. In 1988, Reaven2 noted that several risk factors (eg, dyslipidemia, hypertension, hyperglycemia) commonly cluster together. This clustering he called Syndrome X , and he recognized it as a multiplex risk factor for CVD. Reaven and subsequently others postulated that insulin resistance underlies Syndrome X (hence the commonly used term insulin resistance syndrome ). Other researchers use the term metabolic syndrome for this clustering of metabolic risk factors. ATP III used this alternative term. It avoids the implication that insulin resistance is the primary or only cause of associated risk factors. Although ATP III identified CVD as the primary clinical outcome of the metabolic syndrome, most people with this syndrome have insulin resistance, which confers increased risk for type 2 diabetes. When diabetes becomes clinically apparent, CVD risk rises sharply. Beyond CVD and type 2 diabetes, individuals with metabolic syndrome seemingly are susceptible to other conditions, notably polycystic ovary syndrome, fatty liver, cholesterol gallstones, asthma, sleep disturbances, and some …

1,252 citations

Journal ArticleDOI
TL;DR: With few exceptions, within the 3 BMI categories, those with high WC values were increasingly likely to have hypertension, diabetes, dyslipidemia, and the metabolic syndrome compared with those with normal WC values.
Abstract: Background No evidence supports the waist circumference (WC) cutoff points recommended by the National Institutes of Health to identify subjects at increased health risk within the various body mass index (BMI; calculated as weight in kilograms divided by the square of height in meters) categories. Objective To examine whether the prevalence of hypertension, type 2 diabetes mellitus, dyslipidemia, and the metabolic syndrome is greater in individuals with high compared with normal WC values within the same BMI category. Methods The subjects consisted of 14 924 adult participants of the Third National Health and Nutrition Examination Survey, which is a nationally representative cross-sectional survey. Subjects were grouped by BMI and WC in accordance with the National Institutes of Health cutoff points. Within the normal-weight (18.5-24.9), overweight (25.0-29.9), and class I obese (30.0-34.9) BMI categories, we computed odds ratios for hypertension, diabetes, dyslipidemia, and the metabolic syndrome and compared subjects in the high-risk (men, >102 cm; women, >88 cm) and normal-risk (men, ≤102 cm; women, ≤88 cm) WC categories. Results With few exceptions, within the 3 BMI categories, those with high WC values were increasingly likely to have hypertension, diabetes, dyslipidemia, and the metabolic syndrome compared with those with normal WC values. Many of these associations remained significant after adjusting for the confounding variables (age, race, poverty-income ratio, physical activity, smoking, and alcohol intake) in normal-weight, overweight, and class I obese women and overweight men. Conclusions The National Institutes of Health cutoff points for WC help to identify those at increased health risk within the normal-weight, overweight, and class I obese BMI categories.

1,025 citations