Effects of 1,144 km of road cycling performed in 7 days: a cardiometabolic imaging study.

This cardiometabolic imaging study was designed to document the adaptation of middle-aged recreational cyclists to a large exercise prescription not aiming at weight loss. Eleven middle-aged recreational male cyclists traveled 1,144 km over seven consecutive days. A comprehensive cardiometabolic profile including visceral and ectopic adiposity assessed by magnetic resonance imaging was obtained at baseline and following the exercise week. Cardiorespiratory fitness (CRF) was measured using maximal cardiopulmonary exercise testing. During the week, heart rate was monitored to calculate individual energy expenditure. Baseline characteristics of cyclists were compared with 86 healthy males in the same age range. Cyclists presented higher baseline CRF (+9.2 mL/kg/min, P < 0.0001) and lower subcutaneous (-56.2 mL, P < 0.05) and liver (-3.3%, P < 0.05) fat compared with the reference group. Despite the large energy expenditure during the cycling week, the increase in energy intake limited decreases in body weight (-0.8 ± 0.9 kg, P < 0.05) and body mass index (-0.3 ± 0.3 kg/m2, P < 0.05). Loss of fat mass (-1.5 ± 1.0 kg, P < 0.001) and a trend toward an increased lean mass (+0.8 ± 1.2 kg, P < 0.07) were observed. Visceral adiposity (-14.1 ± 14.2 mL, P < 0.01) and waist circumference (-3.2 ± 1.7 cm, P < 0.0001) decreased, whereas subcutaneous (-2.7 ± 5.1 mL, NS), liver (-0.5 ± 0.9%, NS), and cardiac (-0.3 ± 2.3 mL, NS) fat remained unchanged. This cardiometabolic imaging study documents middle-aged recreational cyclists' subcutaneous and visceral adiposity as well as cardiac and liver fat responses to a large volume of endurance exercise despite an increase in energy intake aimed at limiting weight loss.NEW & NOTEWORTHY Even when being accompanied by a substantial increase in energy intake to compensate energy expenditure and limit weight loss, a large volume of endurance exercise performed within a short period of time is associated with a significant reduction in visceral adiposity. High cardiorespiratory fitness is associated with low levels of liver fat in middle-aged males.

Associations of insulin-like growth factor binding protein-2 with metabolic profile and hepatic fat deposition in asymptomatic men and women.

Low circulating levels of insulin-like growth-factor binding protein-2 (IGFBP-2) have been associated with increased adiposity and metabolic alterations such as insulin resistance, dyslipidemia, and nonalcoholic fatty liver disease in individuals with obesity. However, whether IGFBP-2 affects energy metabolism in the early stages of these disorders remains unclear. Herein, we hypothesized that plasma IGFBP-2 concentrations are inversely associated with early liver fat accumulation and alterations in lipid and glucose homeostasis in apparently healthy and asymptomatic men and women. Three hundred thirty-three middle-aged Caucasian men and women apparently healthy and without cardiovascular symptoms were enrolled for a cross-sectional cardiometabolic imaging study. Individuals with BMI ≥ 40 kg/m2, cardiovascular disease, dyslipidemia, hypertension, and diabetes were excluded. Fasting glucose and lipid profiles were measured and an oral glucose tolerance test was performed. Liver fat content was assessed by magnetic resonance spectroscopy. Volume of visceral adipose tissue (VAT) was evaluated by magnetic resonance imaging. Plasma IGFBP-2 levels were quantified by ELISA. Participants with low IGFBP-2 levels were characterized by a higher body fat mass (P < 0.0001), insulin resistance (P < 0.0001), higher plasma triglyceride (TG) (P < 0.0001), and lower HDL-cholesterol levels (P < 0.0001) in a sex-independent manner. IGFBP-2 levels were inversely correlated with hepatic fat fraction in both men (r = -0.36, P < 0.0001) and women (r = -0.40, P < 0.0001). IGFBP-2 concentrations were negatively associated with hepatic fat fraction independently of age and VAT in both men (R2 = 0.23, P = 0.012) and women (R2 = 0.27, P = 0.028). In conclusion, our findings show that even in asymptomatic, apparently healthy individuals, low IGFBP-2 levels are associated with a more deteriorated cardiometabolic risk profile and with a high hepatic fat content in a VAT-independent manner. However, IGFBP-2 does not appear to influence the established sexual dimorphism observed for metabolic variables and hepatic fat fraction. Additional studies are required to better understand the relationships between IGFBP-2 and liver fat content.NEW & NOTEWORTHY Faced with a paucity of reliable clinical etiologic markers for fatty liver, this research article demonstrates, for the first time, that low blood levels of the protein IGFBP-2 are associated with a more deteriorated cardiometabolic risk profile and with a high hepatic fat content independently of visceral fat volume and sex, even in asymptomatic, apparently healthy individuals.

Overweight, Obesity, and CVD Risk: a Focus on Visceral/Ectopic Fat.

PURPOSE OF REVIEW: Despite its prevalence and well-documented impact on population health, obesity has not emerged as a strong independent risk factor for cardiovascular disease after control for intermediate risk factors. The purpose of this brief narrative review is to highlight results from imaging studies that have not only documented the remarkable heterogeneity of body fat topography but also the importance of visceral adiposity as a key body fat depot associated with cardiovascular disease risk and type 2 diabetes. RECENT FINDINGS: Simple tools are also discussed in order to refine cardiometabolic risk assessment in persons with overweight/obesity. It is proposed that four lifestyle vital signs should be considered in clinical practice to improve discrimination of health risk in individuals with overweight/obesity: waist circumference as a simple marker of abdominal adiposity, cardiorespiratory fitness, overall diet quality, and level of reported physical activity. Heterogeneity of obesity is proposed as an example of a condition that would benefit from a precision lifestyle medicine approach.

Relationships between circulating 25(OH) vitamin D, leptin levels and visceral adipose tissue volume: results from a 1-year lifestyle intervention program in men with visceral obesity.

BACKGROUND/OBJECTIVES: Obesity has been associated with elevated leptinemia and vitamin D deficiency. To date, whether there is an association between vitamin D and leptin levels independent from adiposity remains uncertain. Our objective was to investigate the associations between changes in 25(OH) vitamin D levels, changes in adiposity variables, and changes in leptin levels produced by a 1-year lifestyle intervention program. SUBJECTS/METHODS: Sedentary men (n = 113) with abdominal obesity, dyslipidemic, and non-vitamin D supplemented were involved in a 1-year lifestyle modification program. Subjects were individually counseled by a kinesiologist and a nutritionist once every 2 weeks during the first 4 months with subsequent monthly visits in order to elicit a 500 kcal daily energy deficit and to increase physical activity/exercise habits. Adiposity mapping by computed tomography and cardiometabolic biomarkers, as well as vitamin D measurements were performed at baseline and at the 1-year visit. RESULTS: The 1-year intervention resulted in a 26% decrease in visceral adipose tissue volume (from 1951 ± 481 to 1463 ± 566 cm3), a 27% decrease in leptin levels (from 12.0 ± 8.1 to 8.5 ± 7.8 ng/mL) and a 27% increase in plasma 25(OH) vitamin D concentrations (from 50 ± 18 to 60 ± 18 nmol/L, p < 0.0001). One-year increases in 25(OH) vitamin D levels were inversely correlated with 1-year changes in leptin levels (r = -0.41, p < 0.001). The association remained significant after adjustment for 1-year changes in various adiposity indices: visceral adipose tissue (r = -0.30, p = 0.0019), subcutaneous adipose tissue (r = -0.35, p = 0.0004), total abdominal adipose tissue (r = -0.31, p = 0.0015), and fat mass (r = -0.31, p = 0.001). CONCLUSIONS: In response to a 1-year lifestyle intervention, changes in 25(OH) vitamin D levels were independently associated with changes in leptinemia after adjustment for adiposity changes. This finding supports a possible physiological link between leptinemia and 25(OH) vitamin D levels independent from adiposity and underscores the role of lifestyle modifications leading to lowered leptinemia in the clinical management of vitamin D deficiency.

Changes in circulating vitamin D levels with loss of adipose tissue.

PURPOSE OF REVIEW: Low vitamin D levels have been extensively reported in obesity. Thus, the pandemic of obesity has been paralleled by a high prevalence of low vitamin D status. Given the well documented associations linking poor vitamin D status to adverse health outcomes (diabetes, cardiovascular disease, cancers, all-cause mortality), a proper understanding of the mechanisms linking excess adiposity to low vitamin D status is key to identify and implement effective interventions to replenish vitamin D levels in obese individuals. In this review, we will discuss recent literature investigating the effects of adipose tissue volume loss through energy restriction and/or physical activity on circulating 25-hydroxyvitamin D [25(OH)D] levels. RECENT FINDINGS: Improvements of circulating 25(OH)D levels with adiposity loss through lifestyle interventions without supplementation is being reported by a growing number of studies, including recent randomized controlled trials. SUMMARY: Low 25(OH)D is one of the metabolic disturbances associated with excess adiposity, particularly visceral adiposity. Recommendations for the treatment of obesity-related vitamin D deficiency should emphasize the role of visceral adiposity loss through healthy lifestyle habits, in conjunction with weight-adjusted vitamin D supplementation, not only to replenish 25(OH)D levels but also to address other visceral adiposity-related disturbances, such as insulin resistance, inflammation, hypertension, and dyslipidemia.

Long-Term Improvement in Cardiorespiratory Fitness Ameliorates Insulin Sensitivity beyond Changes in Visceral/Ectopic Fat among Men with Visceral Obesity.

The SYNERGIE study documented the effects on cardiometabolic risk (CMR) indices of a 1-year lifestyle intervention targeting physical activity (PA) and diet followed by a 2-year maintenance period in men with visceral obesity. Improvements in CMR markers and a decrease in low-attenuation muscle (LAM) area were observed after 1 year. Despite a rebound in visceral adipose tissue (VAT) during the maintenance period, insulin resistance (IR) improved. We tested the hypothesis that variations in cardiorespiratory fitness (CRF) and LAM could explain the long-term improvement in IR. A health (n = 88; mean age 49.0 ± 8.2 years) and fitness (n = 72) evaluation was performed at 0, 1, and 3 years. Participants were classified into two groups based on their CRF response over the maintenance period (worsening: CRF- vs. maintenance/improvement: CRF+). During the maintenance period, changes in the psoas and core LAM areas correlated with changes in IR (r = 0.27; p < 0.05 and r = 0.34; p < 0.005) and changes in CRF (r = -0.31; p < 0.01 and r = -0.30; p < 0.05). IR improved in the CRF+ group (p < 0.05) but remained stable in the CRF- group. Men in the CRF+ group regained half of the changes in VAT volume and LAM at the psoas and mid-thigh compared to the CRF- group (p < 0.05). These results support the importance of targeting VAT and CRF/PA for the long-term management of CMR in men with visceral obesity.

Combination of Waist Circumference and Circulating Levels of IGFBP-2 as a Simple Screening Tool for Early Detection of Metabolic Dysfunction-Associated Steatotic Liver Disease.

Optimal non-invasive biomarkers for metabolic dysfunction-associated steatotic liver disease (MASLD) remain elusive, especially in the detection of early stages. This study tested in an asymptomatic cohort of 171 men (49.2 ± 8.6 years) and 131 women (51.8 ± 8.5 years) whether waist circumference (WC) and circulating levels of insulin-like growth factor-binding protein 2 (IGFBP-2) could identify individuals with liver fat >5% as assessed by magnetic resonance spectroscopy. Participants with high WC (> 85 or 90 cm for women and men, respectively) and low IGFBP-2 (< 260 or 230 ng/mL for women and men, respectively) were characterized by a higher risk of having MASLD (46.3%, p < 0.0001). Among the 68 individuals with MASLD, 73.5% fell into the subgroup with high WC and low IGFBP-2 concentrations (p < 0.0001). When combined, these markers reached a sensitivity of 73.5% and specificity of 75.2% for MASLD. Thus, WC and plasma IGFBP-2 levels might be useful as a novel, simple, and non-invasive index to support existing tools in the identification of individuals at risk of early-stage MASLD.

Leisure-time physical activity is more strongly associated with cardiometabolic risk than occupational physical activity: Results from a workplace lifestyle modification program.

BACKGROUND: Regular physical activity (PA) plays a key role in the management and prevention of numerous chronic diseases. However, recent studies have suggested that occupational physical activity (OPA) may not always have health benefits. The aim of the present study was to examine the respective contributions of OPA vs. leisure-time physical activity (LTPA) to the variation in the cardiometabolic profile, including cardiorespiratory fitness (CRF), of employees involved in a workplace lifestyle modification program. Our study hypothesis was that LTPA would show a stronger association with indices of cardiometabolic health than OPA. METHODS: A mobile health assessment unit was used to assess 5145 workers (3397 men and 1748 women) on site at their workplace. Assessments included lifestyle questionnaires (overall diet quality, type of OPA and level of LTPA), blood pressure measurements, blood tests, anthropometric measurements, and a submaximal treadmill exercise test to assess CRF. Results were adjusted for education, household income and age. RESULTS: When workers were classified on the basis of their OPA (sedentary work, standing work, physical work, and heavy manual work), only a few significant differences in the cardiometabolic profile were observed in men, with those in the physical work category having more favorable values than sedentary workers. However, substantial and significant differences were observed among employees classified on the basis of their LTPA, these differences being observed in both men and women. For instance, waist circumference, the cholesterol/HDL cholesterol ratio, triglyceride concentrations and resting heart rate were lower in active individuals compared to inactive and moderately inactive individuals (p < 0.01). Furthermore, irrespective of whether or not employees were sedentary at work, a high level of LTPA was associated with a greater CRF (p < 0.001). Finally, we found that the lowest prevalence of hypertriglyceridemic waist (p < 0.01) and the highest score of overall diet quality (p < 0.001) were observed in active individuals, irrespective of their OPA category. CONCLUSION: Levels of LTPA were more strongly associated with cardiometabolic health than OPA in a cohort of blue- and white-collar employees. Furthermore, high levels of LTPA were found to counteract the potentially deleterious effects of a sedentary work on cardiometabolic health.

Plasma IGFBP-2 levels reveal heterogeneity in hepatic fat content in adults with excess visceral adiposity.

Lay summary: Obesity is frequently accompanied by a fatty liver. However, some individuals with high abdominal fat levels nevertheless have low levels of liver fat. Reasons for such discordant phenotypes are unclear. In this paper, we report that among asymptomatic individuals with high levels of visceral fat, low concentrations of IGFBP-2 in the circulation were associated with significantly higher hepatic fat content compared to those with high IGFBP-2 levels. We conclude that quantification of plasma IGFBP-2 concentrations may be useful to identify the early risk for liver fat accumulation in apparently healthy individuals without cardiovascular symptoms. Aim/hypothesis: Although excess visceral adiposity (VAT) is generally associated with increased liver fat (LF), recent evidence has revealed heterogeneity in LF content among adults with visceral obesity, potentially contributing to specific differences in cardiometabolic outcomes. Reasons for such discordant VAT-LF phenotypes are largely unknown. The present study aimed at assessing whether circulating levels of insulin growth-factor binding protein-2 (IGFBP-2) could be a useful biomarker in the identification of heterogenous and discordant VAT-LF phenotypes. Methods: A sample of 308 middle-aged Caucasian apparently healthy men and women without cardiovascular symptoms were studied for the present cross-sectional analyses. Fasting plasma glucose and lipid levels were assessed and an oral glucose tolerance test was performed. Hepatic fat fraction (HFF) was measured using magnetic resonance spectroscopy whereas VAT was assessed by magnetic resonance imaging. Plasma IGFBP-2 levels were quantified by ELISA. Participants were then classified on the basis of median VAT (81 mL) and IGFBP-2 levels (233 ng/mL). Results: Individuals with high levels of VAT were characterized by higher waist circumference, lower insulin sensitivity, as well as by higher plasma triglyceride and lower HDL-cholesterol levels. Plasma IGFBP-2 levels were inversely correlated with HFF (r = -0.39, p < 0.0001). Among men and women with high levels of VAT, those with low levels of IGFBP-2 had significantly higher HFF (7.5 ± 0.7%), compared to participants with high IGFBP-2 concentrations (3.2 ± 0.5%, p < 0.0001). Conclusion: In the presence of excess VAT, high IGFBP-2 concentrations are associated with low levels of LF. Although additional studies will be necessary to establish causality and further clarify the clinical implications of these observations, these findings are concordant with a novel function of IGFBP-2 in modulating susceptibility to non-alcoholic fatty liver disease (NAFLD) in the presence of visceral obesity.

Abdominal obesity and metabolic syndrome.

Metabolic syndrome is associated with abdominal obesity, blood lipid disorders, inflammation, insulin resistance or full-blown diabetes, and increased risk of developing cardiovascular disease. Proposed criteria for identifying patients with metabolic syndrome have contributed greatly to preventive medicine, but the value of metabolic syndrome as a scientific concept remains controversial. The presence of metabolic syndrome alone cannot predict global cardiovascular disease risk. But abdominal obesity - the most prevalent manifestation of metabolic syndrome - is a marker of 'dysfunctional adipose tissue', and is of central importance in clinical diagnosis. Better risk assessment algorithms are needed to quantify diabetes and cardiovascular disease risk on a global scale.

Intra-abdominal adipose depot variation in adipogenesis, lipogenesis, angiogenesis, and fibrosis gene expression and relationships with insulin resistance and inflammation in premenopausal women with severe obesity.

Although severe obesity is associated with insulin resistance (IR) and inflammation, secretory function of intra-abdominal adipose tissues and their relationships with IR and inflammation markers remain poorly understood. Aims were to measure gene expression of adipogenic (C/EBPα/ß, PPARγ-1/2, SREBP-1c, LXRα), lipogenic (SCD1, DGAT-1/2), angiogenic (VEGFα, leptin), and fibrotic (LOX, COL6A3) factors in the round ligament (RL), omental (OM), and mesenteric (ME) fat depots and to evaluate their relationships with IR and inflammation markers in 48 women with severe obesity undergoing bariatric surgery. Gene expression was assessed by RT-qPCR, and plasma glucose and insulin (HOMA-IR calculated), PAI-1, IL-6, TNFα, adiponectin, and leptin levels were determined. C/EBPß and PPARγ-1/2 mRNA levels were more expressed in the OM (0.001

Targeting Diet Quality at the Workplace: Influence on Cardiometabolic Risk.

The American Heart Association criteria for cardiovascular health include overall diet quality (DQ). The present study evaluated the effect of a workplace health promotion program targeting DQ and physical activity on features of cardiometabolic risk (CMR). Before and after the 3-month intervention, 2260 employees (1462 men and 798 women) completed a health and fitness evaluation including assessment of DQ using a validated food-based questionnaire. After the 3-month lifestyle modification program, DQ increased significantly in both sexes (p < 0.0001) as well as physical activity level (p < 0.0001). A reduction in waist circumference (p < 0.0001) and improved lipid levels were also observed. Significant associations were found between changes in DQ index and changes in CMR variables in both men (standardized regression coefficients ranged from -0.19 (95% confidence interval: -0.26 to -0.12) to -0.29 (95% confidence interval: -0.34 to -0.25)) and women (standardized regression coefficients ranged from -0.18 (95% confidence interval: -0.25 to -0.11) to -0.27 (95% confidence interval: -0.41 to -0.13)). Multiple linear regression analyses showed a significant contribution of changes in the DQ index to the variation in some CMR variables, independent from changes in physical activity level and cardiorespiratory fitness. This study provides evidence that targeting DQ at the workplace is relevant to improve cardiometabolic health.

CT-derived abdominal adiposity: Distributions and better predictive ability than BMI in a nationwide study of 59,429 adults in China.

BACKGROUND: Although abdominal adiposity is associated with an altered cardiometabolic risk profile, the specific contribution of abdominal adipose tissue distribution remains not fully understood. Computed tomography (CT) is a well-established and precise method to measure abdominal adipose tissue distribution. The present study investigated abdominal adiposity assessed by CT in a large-scale Chinese population. METHOD: A total of 59,429 adults who underwent a low dose chest CT for lung cancer screening at one of 13 health checkup centers throughout China were evaluated. Abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) areas were measured at the center of the 2nd lumbar vertebra with Mindways quantitative CT software using the existing CT dataset without any additional radiation exposure. The ratio of visceral to total adipose tissue (TAT) areas (VAT/TAT ratio) was calculated and expressed as a percentage. Anthropometric indices including body mass index (BMI) and waist circumference were also obtained. RESULTS: BMI, waist circumference, VAT area, SAT area, and the VAT/TAT ratio were 25.0 ±â€¯3.0 kg/m2, 90 ±â€¯8 cm, 194 ±â€¯77 cm2, 85 ±â€¯41 cm2, and 69.5 ±â€¯9.1%, respectively, in men and 23.3 ±â€¯3.1 kg/m2, 79 ±â€¯8 cm, 120 ±â€¯57 cm2, 123 ±â€¯53 cm2, and 48.9 ±â€¯9.7% in women. With increasing age, VAT area and the VAT/TAT ratio increased in both sexes whereas SAT area decreased in men (P < 0.001 for all). After adjustment for BMI and waist circumference, older individuals showed higher VAT area and higher VAT/TAT ratio than younger subjects (P < 0.001 for all). Adjusted VAT areas in participants aged 75 or older was 45 cm2 (95% confidence interval [CI]: 41 cm2, 50 cm2) higher in men and 43 cm2 (95% CI: 37 cm2, 49 cm2) higher in women compared with participants aged 31-44 years. Additionally, differences in VAT area across age groups increased as BMI or waist circumference increased. VAT and SAT areas, but not the VAT/TAT ratio, were positively associated with BMI and waist circumference in every age group. CONCLUSION: In a nationwide study conducted in China, distributions of CT-derived measures of visceral and subcutaneous adiposity were found to vary significantly between sex and age groups. Our study also revealed that the proportion of VAT (an important driver of cardiometabolic risk) could not be predicted from BMI in a Chinese population.

Comparison between gradient gel electrophoresis and nuclear magnetic resonance spectroscopy in estimating coronary heart disease risk associated with LDL and HDL particle size.

BACKGROUND: Gradient gel electrophoresis (GGE) and nuclear magnetic resonance (NMR) spectroscopy are both widely accepted methods for measuring LDL and HDL particle size. However, whether or not GGE- or NMR-measured LDL or HDL particle size predicts coronary heart disease (CHD) risk to a similar extent is currently unknown. METHODS: We used GGE and NMR to measure LDL and HDL particle size in a nested case-control study of 1025 incident cases of CHD and 1915 controls from the EPIC (European Prospective Investigation into Cancer and Nutrition)-Norfolk study. The study sample included apparently healthy men and women age 45-79 years followed for an average of 6 years. RESULTS: Pearson correlation coefficients showed that the overall agreement between NMR and GGE was better for the measurement of HDL size (r = 0.78) than for LDL size (r = 0.47). The odds ratio for future CHD among participants in the bottom tertile of LDL size (smallest LDL particles) was 1.35 (95% CI, 1.12-1.63) for GGE and 1.74 (1.41-2.15) for NMR. For HDL size, these respective odds ratios were 1.41 (1.16-1.72) and 1.85 (1.47-2.32). After adjustment for potential confounders, the relationship between small LDL or HDL particles and CHD was no longer significant, irrespective of the method. CONCLUSIONS: In this prospective population study, we found that the relationships between NMR-measured LDL and HDL sizes and CHD risk were slightly higher than those obtained with GGE.

Plasma soluble tumour necrosis factor-alpha receptor 2 is elevated in obesity: specific contribution of visceral adiposity.

OBJECTIVE: We examined the obesity phenotype most strongly associated with increased plasma concentrations of sTNFR2, and compared which of the two markers, TNF-alpha or sTNFR2, better predicts indices of plasma glucose-insulin homeostasis. DESIGN, PATIENTS AND MEASUREMENTS: Plasma sTNFR2 levels were measured in a sample of 287 healthy nondiabetic men [age: 43.9 +/- 8.0 years (mean +/- SD)], covering a wide range of adiposity values (BMI: 29.0 +/- 4.4 kg/m(2); waist girth: 100.0 +/- 11.7 cm). RESULTS: Plasma sTNFR2 levels correlated positively and significantly with BMI (r = 0.36; P < 0.0001), fat mass (r = 0.42; P < 0.0001), waist girth (r = 0.38; P < 0.0001) as well as with visceral (r = 0.37; P < 0.0001) and subcutaneous adipose tissue (AT) (r = 0.40; P < 0.0001) areas measured by computed tomography. Two subgroups (n = 27 in each group) of overweight men (BMI >or=25 kg/m(2)) were individually matched for similar BMI values, but with markedly different levels of visceral AT (< or >or=130 cm(2)) and then compared with a control group of 46 lean subjects (with both BMI <25 kg/m(2) and visceral AT <130 cm(2)). This analysis revealed that men characterized by high levels of visceral AT had significantly higher concentrations of sTNFR2 compared with obese men with low visceral AT (1861 +/- 457 pg/ml vs. 1722 +/- 400; P < 0.05) and with lean controls (1570 +/- 291 pg/ml; P < 0.001). Whereas subjects classified across tertiles of TNF-alpha levels showed no difference in glucose tolerance and insulin levels, subjects in the upper tertile of plasma sTNFR2 levels were characterized with the highest plasma insulin concentrations during the OGTT and had the highest area under the curve of insulin concentrations. CONCLUSIONS: These results indicate that sTNFR2 levels are more closely related to abdominal AT accumulation than to total adiposity. Furthermore, plasma concentrations of sTNFR2 are independently related to plasma glucose-insulin homeostasis beyond the known contribution of visceral adiposity.

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.

The hypertriglyceridemic-waist phenotype and the risk of coronary artery disease: results from the EPIC-Norfolk prospective population study.

BACKGROUND: Screening for increased waist circumference and hypertriglyceridemia (the hypertriglyceridemic-waist phenotype) has been proposed as an inexpensive approach to identify patients with excess intra-abdominal adiposity and associated metabolic abnormalities. We examined the relationship between the hypertriglyceridemic-waist phenotype to the risk of coronary artery disease in apparently healthy individuals. METHODS: A total of 21,787 participants aged 45-79 years were followed for a mean of 9.8 (standard deviation 1.7) years. Coronary artery disease developed in 2109 of them during follow-up. The hypertriglyceridemic-waist phenotype was defined as a waist circumference of 90 cm or more and a triglyceride level of 2.0 mmol/L or more in men, and a waist circumference of 85 cm or more and a triglyceride level of 1.5 mmol/L or more in women. RESULTS: Compared with participants who had a waist circumference and triglyceride level below the threshold, those with the hypertriglyceridemic-waist phenotype had higher blood pressure indices, higher levels of apolipoprotein B and C-reactive protein, lower levels of high-density lipoprotein cholesterol and apolipoprotein A-I, and smaller low-density lipoprotein particles. Among men, those with the hypertriglyceridemic-waist phenotype had an unadjusted hazard ratio for future coronary artery disease of 2.40 (95% confidence interval [CI] 2.02-2.87) compared with men who did not have the phenotype. Women with the phenotype had an unadjusted hazard ratio of 3.84 (95% CI 3.20-4.62) compared with women who did not have the phenotype. INTERPRETATION: Among participants from a European cohort representative of a contemporary Western population, the hypertriglyceridemic-waist phenotype was associated with a deteriorated cardiometabolic risk profile and an increased risk for coronary artery disease.

Reversing Type 2 Diabetes: The Time for Lifestyle Medicine Has Come!

The IDF (International Diabetes Federation) Diabetes Atlas Committee has recently published the global estimates of diabetes prevalence for 2019 [...].

Metabolic Syndrome: Past, Present and Future.

Most clinicians and health professionals have heard or read about metabolic syndrome [...].