Search

Aims/hypothesis: Ceramides are sphingolipids that contribute to insulin resistance in preclinical studies. We hypothesised that plasma ceramides would be associated with body fat distribution, insulin resistance and incident type 2 diabetes in a multi-ethnic cohort., Methods: A total of 1557 participants in the Dallas Heart Study without type 2 diabetes underwent measurements of metabolic biomarkers, fat depots by MRI and plasma ceramides by liquid chromatography-mass spectrometry. Diabetes outcomes were assessed after 7 years. Associations of body fat and insulin resistance with ceramides at baseline and of ceramides with incident diabetes outcomes were analysed., Results: The cohort had a mean age of 43 years, with 58% women, 45% black participants and a mean BMI of 28 kg/m 2 . Total cholesterol levels were associated with all ceramides, but higher triacylglycerols and lower HDL-cholesterol and adiponectin were associated only with saturated fatty acid chain ceramides (p < 0.0003). After adjusting for clinical characteristics and total body fat, visceral adipose tissue was positively associated with saturated fatty acid ceramides (per SD, β = 0.16 to 0.18) and inversely associated with polyunsaturated fatty acid ceramides (β = -0.14 to -0.16, p < 0.001 for all). Lower-body subcutaneous fat showed an opposite pattern to that for visceral fat. HOMA-IR was positively associated with saturated (β = 0.08 to 0.09, p < 0.001) and inversely with polyunsaturated ceramides (β = -0.06 to -0.07, p < 0.05). Ceramides were not associated with incident type 2 diabetes after adjustment for clinical factors., Conclusions/interpretation: Plasma ceramides demonstrate a biologically complex relationship with metabolic and imaging indicators of dysfunctional adiposity. The role of ceramides in a shared pathway of metabolic dysfunction linking visceral adiposity and insulin resistance requires further investigation.

Background: The metabolic syndrome is a constellation of risk factors including dyslipidemia, dysglycemia, hypertension, a pro-inflammatory state, and a prothrombotic state. All of these factors are accentuated by obesity. However, obesity can be defined by body mass index (BMI), percent body fat, or by body fat distribution. The latter consists of upper body fat (subcutaneous and visceral fat) and lower body fat (gluteofemoral fat). Waist circumference is a common surrogate marker for upper body fat., Methods: Data from the National Health and Nutrition Examination Survey (NHANES) for the years 1999-2006 was examined for associations of metabolic risk factors with percent body fat, waist circumference, and BMI., Results: Associations between absolute measures of waist circumference and risk factors were similiar for men and women. The similarities of associations between waist circumference and risk factors suggests that greater visceral fat in men does not accentuate the influence of upper body fat on risk factors., Conclusions: Different waist concumference values should not be used to define abdominal obesity in men and women., (© 2018 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Objective: To examine the association between specific adipose tissue depots and the risk of incident cancer in the Dallas Heart Study., Patients and Methods: Individuals without prevalent cancer in the Dallas Heart Study underwent quantification of adipose depots: visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue, and liver fat by magnetic resonance imaging, and subcutaneous lower-body fat (LBF) by dual-energy X-ray absorptiometry from January 1, 2000, through December 31, 2002, and were observed for the development of cancer for up to 12 years. Multivariable Cox proportional hazards modeling was performed to examine the association between fat depots and cancer., Results: Of 2627 participants (median age, 43 years; 69% nonwhite race), 167 (6.4%) developed cancer. The most common primary sites of cancer were the breast (in women) and the prostate (in men). In multivariable models adjusted for age, sex, race, smoking, alcohol use, family history of malignancy, and body mass index, a 1-SD increase in VAT was not associated with increased risk of cancer (hazard ratio [HR], 0.94; 95% CI, 0.77-1.14). In contrast, each 1-SD increase in LBF was associated with a reduced incidence of cancer (HR, 0.69; 95% CI, 0.52-0.92) in the fully adjusted model., Conclusions: In this study, adiposity-associated cancer risk was heterogeneous and varied by fat depot: VAT was not independently associated with incident cancer, and LBF seemed to protect against cancer development. Further studies of the adiposity-cancer relationship, including serial assessments, are needed to better elucidate this relationship., (Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Objective: Visceral (VAT) and abdominal subcutaneous (SAT) adipose tissues contribute to obesity but may have different metabolic and atherosclerosis risk profiles. We sought to determine the associations of abdominal VAT and SAT mass with markers of cardiac and metabolic risk in a large, multiethnic, population-based cohort of obese adults., Design and Methods: Among obese participants in the Dallas Heart Study, we examined the cross-sectional associations of abdominal VAT and SAT mass, assessed by magnetic resonance imaging (MRI) and indexed to body surface area (BSA), with circulating biomarkers of insulin resistance, dyslipidemia, and inflammation (n = 942); and with aortic plaque and liver fat by MRI and coronary calcium by computed tomography (n = 1200). Associations of VAT/BSA and SAT/BSA were examined after adjustment for age, sex, race, menopause, and body mass index., Results: In multivariable models, VAT significantly associated with the homeostasis model assessment of insulin resistance (HOMA-IR), lower adiponectin, smaller LDL and HDL particle size, larger VLDL size, and increased LDL and VLDL particle number (p < 0.001 for each). VAT also associated with prevalent diabetes, metabolic syndrome, hepatic steatosis, and aortic plaque (p < 0.001 for each). VAT independently associated with C-reactive protein but not with any other inflammatory biomarkers tested. In contrast, SAT associated with leptin and inflammatory biomarkers, but not with dyslipidemia or atherosclerosis. Associations between SAT and HOMA-IR were significant in univariable analyses but attenuated after multivariable adjustment., Conclusion: VAT associated with an adverse metabolic, dyslipidemic, and atherogenic obesity phenotype. In contrast, SAT demonstrated a more benign phenotype, characterized by modest associations with inflammatory biomarkers and leptin, but no independent association with dyslipidemia, insulin resistance, or atherosclerosis in obese individuals. These findings suggest that abdominal fat distribution defines distinct obesity sub-phenotypes with heterogeneous metabolic and atherosclerosis risk., (Copyright © 2012 The Obesity Society.)

Background: The relation of body fat distribution to left ventricular (LV) structure and function is poorly defined., Methods and Results: A total of 2710 participants without heart failure or LV dysfunction in the Dallas Heart Study underwent dual energy x-ray absorptiometry and MRI assessment of fat distribution, LV morphology, and hemodynamics. Cross-sectional associations of fat distribution with LV structure and function were examined after adjustment for age, sex, race, comorbidities, and lean mass. Mean age was 44 years with 55% women; 48% blacks; and 44% obese. After multivariable adjustment, visceral adipose tissue was associated with concentric remodeling characterized by lower LV end-diastolic volume (β=-0.21), higher concentricity (β=0.20), and wall thickness (β=0.09; P<0.0001 for all). In contrast, lower body subcutaneous fat was associated with higher LV end-diastolic volume (β=0.48), reduced concentricity (β=-0.50), and wall thickness (β=-0.28, P<0.0001 for all). Visceral adipose tissue was also associated with lower cardiac output (β=-0.10, P<0.05) and higher systemic vascular resistance (β=0.08, P<0.05), whereas lower body subcutaneous fat associated with higher cardiac output (β=0.20, P<0.0001) and lower systemic vascular resistance (β=-0.18, P<0.0001). Abdominal subcutaneous fat showed weaker associations with concentric remodeling and was not associated with hemodynamics. Among the subset of obese participants, visceral adipose tissue, but not abdominal subcutaneous fat, was significantly associated with concentric remodeling., Conclusions: Visceral adipose tissue, a marker of central adiposity, was independently associated with concentric LV remodeling and adverse hemodynamics. In contrast, lower body subcutaneous fat was associated with eccentric remodeling. The impact of body fat distribution on heart failure risk requires prospective study.

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 < .05 for each) but not with measurements of general adiposity., 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.