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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/m2. 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. [ABSTRACT FROM AUTHOR]

Abstract: 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. [ABSTRACT FROM AUTHOR]

Background: Previous studies that reported an association of dietary Na+ intake with metabolic syndrome were limited by the use of imprecise measures of obesity, Na+ intake, or exclusion of multiethnic populations. The effect of dietary K+ intake on obesity is less well described. Objective: We hypothesized that high dietary Na+ and low K+, based on the ratio of urinary Na+ to K+ (U[Na+]/[K+]) in a first-void morning urinary sample, is independently associated with total body fat. Design: In a prospective population-based cohort, 2782 participants in the community-dwelling, probability-sampled, multiethnic Dallas Heart Study were analyzed. The primary outcome established a priori was total-body percentage fat (TBPF) measured by dual-energy X-ray absorptiometry. The main predictor was U[Na+]/[K+]. Robust linear regression was used to explore an independent association between U[Na+]/[K+] and TBPF. The analyses were stratified by sex and race after their effect modifications were analyzed. Results: Of the cohort, 55.4% were female, 49.8% African American, 30.8% white, 17.2% Hispanic, and 2.2% other races. The mean (6SD) age was 44 6 10 y, BMI (in kg/m2) was 30 6 7, TBPF was 32 6 10%, and U[Na+]/[K+] was 4.2 6 2.6; 12% had diabetes. In the unadjusted and adjusted models, TBPF increased by 0.75 (95% CI: 0.25, 1.25) and 0.43 (0.15, 0.72), respectively (P = 0.003 for both), for every 3-unit increase in U[Na+]/[K+]. A statistically significant interaction was found between race and U[Na+] /[K+], so that the non-African American races had a higher TBPF than did the African Americans per unit increase in U[Na+]/[K+] (P-interaction, 0.0001 for both). No interaction was found between sex and U[Na+]/[K+]. Conclusions: The ratio of dietary Na+ to K+ intake may be independently associated with TBPF, and this association may be more pronounced in non-African Americans. Future studies should explore whether easily measured spot U[Na+]/[K+] can be used to monitor dietary patterns and guide strategies for obesity management. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: Although psychosocial stress can result in adverse health outcomes, little is known about how perceptions of neighborhood conditions, a measure of environment-derived stress, may impact obesity. The association between perceptions of neighborhood environment and obesity (defined as body mass index [BMI] ≥ 30 kg/m2) among 5,907 participants in the Dallas Heart Study, a multi-ethnic, probability-based sample of Dallas County residents was examined. Design and Methods: Participants were asked to respond to 18 questions about perceptions of their neighborhood. Factor analysis was used to identify three factors associated with neighborhood perceptions: neighborhood violence, physical environment, and social cohesion. Logistic regression analyses were performed to determine the relationship between each factor (higher quintile = more unfavorable perceptions) and the odds of obesity. Results: Decreasing age, income, and education associated with unfavorable overall neighborhood perceptions and unfavorable perceptions about specific neighborhood factors ( P trend <0.05 for all). Increasing BMI was associated with unfavorable perceptions about physical environment ( P trend <0.05) but not violence or social cohesion. After adjustment for race, age, sex, income, education, and length of residence, physical environment perception score in the highest quintile remained associated with a 25% greater odds of obesity (OR 1.25, [95% CI 1.03-1.50]). Predictors of obesity related to environmental perceptions included heavy traffic (OR 1.39, [1.17-1.64]), trash/litter in neighborhood (OR 1.27, [1.01-1.46]), lack of recreational areas (OR 1.21, [1.01-1.46]), and lack of sidewalks (OR 1.25, [95% CI 1.04-1.51]). Conclusions: Thus, unfavorable perceptions of environmental physical conditions are related to increased obesity. Efforts to improve the physical characteristics of neighborhoods, or the perceptions of those characteristics, may assist in the prevention of obesity in this community. [ABSTRACT FROM AUTHOR]

The article discusses the long term outcome of bariatric surgery. It reports that sustained weight loss, lower incidences of cardiovascular diseases, diabetes and cancer are some of the benefits from bariatric surgery. The study was conducted in obese controlled Swedish subjects. During a follow up of 20 years following the bariatric procedure, the surgery patients used a 54 mean cumulative hospital days against the 40 days of the control group at a confidence interval (C.I.) of 95 percent. However, the study highlights that the drug costs from the seventh year were lower for patients who underwent the surgery than control patients.

Periwal V, Chow CC, Bergman RN, Ricks M, Vega GL, Sumner AE. Evaluation of quantitative models of the effect of insulin on lipolysis and glucose disposal. Am J Physiol Regul Integr Comp Physiol 295: R1089-R1096, 2008. First published August 6, 2008; doi:l0.1152/ajpregu.90426.2008.-The effects of insulin on the suppression of lipolysis are neither fully understood nor quantified. We examined a variety of mathematical models analogous to the minimal model of glucose disposal (MMG) to quantify the combined influence of insulin on lipolysis and glucose disposal during an insulin-modified frequently sampled intravenous glucose tolerance test. The tested models, which include two previously published ones, consisted of separate compartments for plasma free fatty acids (FFA), glucose, and insulin. They differed in the number of compartments and in the action of insulin to suppress lipolysis that decreased the plasma FFA level. In one category of models, a single insulin compartment acted on both glucose and FFA simultaneously. In a second category, there were two insulin compartments, each acting on FFA and glucose independently. For each of these two categories, we tested 11 variations of how insulin suppressed lipolysis. We also tested a model with an additional glucose compartment that acted on FFA. These 23 models were fit to the plasma FFA and glucose concentrations of 102 subjects individually. Using Bayesian model comparison methods, we selected the model that best balanced fit and minimized model complexity. In the best model, insulin suppressed lipolysis via a Hill function through a remote compartment that acted on both glucose and FFA simultaneously, and glucose dynamics obeyed the classic MMG. [ABSTRACT FROM AUTHOR]

Primary objective: To determine if plasma levels of 24S-hydroxycholesterol, the primary catabolite of brain cholesterol, provide a measure of axonal damage in acute brain trauma. Research design: Determination of plasma 24S-hydroxycholesterol in a series of persons admitted to an intensive care unit for treatment of closed head injury. Methods and procedures: Levels of 24-S-hydroxycholesterol, 27-hydroxycholesterol, lathosterol and total cholesterol were measured in peripheral blood from 38 persons from 14-55 years of age treated by craniotomy and ventriculostomy for intractable intracerebral hypertension. Severity of brain injury was estimated by the Glasgow Coma Scale (range = 3-13, median = 6 points) and overall injury by the Injury Severity Scale (range = 10-48, median = 29). All subjects were intubated and anaesthetized with intravenous propofol. Plasma sterol levels were compared with those of age-matched control subjects. Outcomes and results: There was no significant increase in plasma 24-S-hydroxycholesterol in subjects with head injury, but measures of peripheral cholesterol synthesis were markedly reduced as compared with values for age-matched normal control subjects. Conclusion: Plasma 24S-hydroxycholesterol levels do not change with severe closed head injury. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) has been termed a “coronary disease equivalent”, yet data suggest that only those DM subjects with metabolic syndrome (MetS) are at increased coronary risk.Using data from the Dallas Heart Study, a large, probability-based population study, we assessed the individual and joint associations between MetS, DM and atherosclerosis, defined as coronary artery calcium (CAC) detected by electron-beam computerised tomography (EBCT) and abdominal aortic plaque (AAP) detected by magnetic resonance imaging.Among 2,735 participants, the median age was 44 years; 1,863 (68%) were non-white; 1,509 (55%) were women; 697 (25.5%) had MetS without DM; 53 (1.9%) had DM without MetS; and 246 (9.0%) had both DM and MetS. The prevalence of CAC increased from those with neither MetS nor DM (16.6%) to MetS only (24.0%) to DM only (30.2%) to both MetS and DM (44.7%) (ptrend <0.0001). The prevalence of CAC was higher in those with both DM and MetS versus either alone (p<0.0001). After adjustment, MetS and DM were each independently associated with CAC (odds ratio [OR] 1.4, 95% confidence intervals [CI] 1.1–1.8; OR 1.8, 95% CI 1.3–2.5, respectively). Compared with the group without DM or MetS, those with both MetS and DM had the most CAC (adjusted OR 2.3; 95% CI 1.6–3.2). All analyses of AAP yielded qualitatively similar results.In conclusion, both MetS and DM are independently associated with an increased prevalence of atherosclerosis, with the highest observed prevalence in subjects with both DM and MetS. [ABSTRACT FROM PUBLISHER]

An approach to understand quantitative traits was recently proposed based on the finding that nonsynonymous (NS) sequence variants in certain genes are preferentially enriched at one extreme of the population distribution. The NS variants, although individually rare, are cumulatively frequent and influence quantitative traits, such as plasma lipoprotein levels. Here, we use the NS variant technique to demonstrate that genetic variation in NPC1L1 contributes to variability in cholesterol absorption and plasma levels of low-density lipoproteins (LDLs). The ratio of plasma campesterol (a plant sterol) to lathosterol (a cholesterol precursor) was used to estimate relative cholesterol absorption in a population-based study. Nonsynonymous sequence variations in NPCIL1 were five times more common in low absorbers(n = 26 of 256) than in high absorbers (n = 5 of 256) (P < 0.001). The rare variants identified in low absorbers were found in 6% of 1,832 African-Americans and were associated with lower plasma levels of LDL cholesterol (LDL-C) (96 ± 36 mg/dl vs. 105 ± 36 mg/dl; P = 0.005). These data, together with prior findings, reveal a genetic architecture for LDL-C levels that does not conform to current models for quantitative traits and indicate that a significant fraction of genetic variance in LDL-C is due to multiple alleles with modest effects that are present at low frequencies in the population. [ABSTRACT FROM AUTHOR]

The article discusses a study on the misperception of body size as an obstacle to effecting weight loss. Obese subjects from the Dallas Heart Study were examined with African Americans comprising 50% of the study cohort. It concludes that body size misperception is prevalent among obese adults particularly in ethnic minorities and suggests the need for multifaceted intervention to counter the effects of body size misperception. It recommends partnering between physicians and public health advocates to develop treatment programs in their communities.

African Americans often have normal high-density lipoprotein cholesterol (HDL-C) and low triglyceride levels despite insulin resistance and obesity. The higher than expected HDL-C levels are usually attributed to low levels of hepatic triglyceride lipase activity (HTGL). Factors that regulate HTGL in African Americans are not well delineated. In the current study, HTGL levels were examined in relation to body fat (body mass index (BMI) and waist circumference (WC)), insulin resistance indices (fasting plasma insulin and HOMA index) and adiponectin. Sixty-three African Americans (33 Men, 30 Women, median age 31 y, range 20-50 y, median BMI 28.6 kg/m², range 19.7-54.7 kg/m²) had anthropometry and measurement of post-heparin lipase activities (HTGL), plasma HDL-C, triglycerides and plasma adiponectin. HTGL correlated strongly with HDL-C (r =-0.52, P<0.0001) and adiponectin (r = -0.49, P<0.001). HTGL increased with BMI and WC (r =0.297, P=-0.018 and r =0.301, P=0.016, resp). Adiponectin correlated strongly with HDL-C (r =0.50, P<0.0001) and triglycerides (r = -0.493, P<0.001). Four multiple regression models predicted HTGL variability (P<0.001) in the study group: Model 1 with an adjusted R²=0.242 and a linear combination of adiponectin, BMI, and HOMA (log[sub e]); Model 2 (R²=0.229) with adiponectin + BMI + HOMA (log[sub e] + triglycerides (log[sub e]; Model 3 (R²=0.241) with adiponectin + age + BMI and Model 4 (R² =0.215) adiponectin + age + BMI + HOMA (logo + triglycerides (log[sub e]). It is apparent that about 23% of HTGL variability among African Americans can be explained by adiponectin levels in combination with markers of obesity and insulin resistance. In each model, the beta-coefficient for adiponectin with HTGL is in the range of 0.44 to 0.47 (P <0.002) rendering this parameter a major factor in HTGL variability. The data suggests that adiponectin is a strong determinant of HTGL levels and plasma triglyceride levels in African Americans. [ABSTRACT FROM AUTHOR]