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Objective: The aim of this study was to determine the effects of empagliflozin on glycerol-derived hepatic gluconeogenesis in adults with obesity without type 2 diabetes mellitus (T2DM) using oral carbon 13 (13 C)-labeled glycerol.Methods: A randomized, double-blind, placebo-controlled trial was performed in participants with magnetic resonance imaging assessment of body fat and measurement of glycerol-derived 13 C enrichment in plasma glucose by nuclear magnetic resonance spectroscopy following ingestion of [U-13 C3 ]glycerol. Participants were randomized to oral empagliflozin 10 mg once daily or placebo for 3 months. Glycerol-derived 13 C enrichment studies were repeated, and treatment differences in the mean percentage of 13 C glycerol enrichment in glucose were compared using mixed linear models.Results: Thirty-five participants completed the study. Empagliflozin increased glycerol-derived 13 C enrichment between baseline and follow-up by 6.5% (P = 0.005), consistent with less glycerol from visceral adipose tissue (VAT). No difference was found with placebo. Glycerol-derived 13 C enrichment was lower in participants with high VAT compared with low VAT by 12.6% (P = 0.04), but there was no heterogeneity of the treatment effect by baseline VAT. Glycerol-derived 13 C enrichment was inversely correlated with VAT but was not correlated with weight loss.Conclusions: VAT is associated with endogenous glycerol-derived hepatic gluconeogenesis, and empagliflozin reduces endogenous glycerol gluconeogenesis in adults with obesity without T2DM. These findings suggest a mechanism by which sodium-glucose cotransporter 2 inhibitors may prevent T2DM in obesity. [ABSTRACT FROM AUTHOR]

Context While the prevalence of vitamin D deficiency is well described in various populations, limited data are available regarding longitudinal variation in serum 25-hydroxyvitamin D concentrations. Objectives To evaluate the temporal trends in serum 25( OH)D, prevalence of vitamin D deficiency and factors influencing these trends. Participants, Design and Setting: Adults enrolled in the Dallas Heart Study, a longitudinal, probability-based, multiethnic, population study in Dallas, Texas, USA. Main Outcome Measures Prevalence of vitamin D deficiency and predictors of change in serum 25( OH)D. Results A total of 2045 participants had serum 25( OH)D measured on two occasions (2000-2002 and 2007-2009) at a median interval of 7 years. Serum 25( OH)D decreased (42.7-39.4 nmol/L, P<.001) and the prevalence of vitamin D deficiency [25( OH)D <50 nmol/L] increased significantly (60.6%-66.4%, P<.0001) despite vitamin D supplementation increasing over the interval (7.2%-23.0%; P<.0001). In a multivariable model adjusting for sex, race, BMI, age, season of blood draw, smoking and exercise, a greater decline in serum 25( OH)D was noted in men compared with women (−8.0 vs −3.5 nmol/L, P<.0001), in participants of Hispanic ethnicity vs White and Black ethnicity ( P<.0001), in nonobese vs obese participants (−7.2 vs −4.0 nmol/L, P=.005) and in nonusers vs users of vitamin D supplements (−5.7 vs −1.7 nmol/L, P=.032). Conclusions Despite increased vitamin D supplementation, serum 25( OH)D decreased in an ethnically diverse cohort of Dallas County residents between 2000-2002 and 2007-2009. Features most predictive of a decline in serum 25( OH)D include male sex, Hispanic ethnicity and weight gain. [ABSTRACT FROM AUTHOR]

Background Some cardiac transplant programs may upgrade listed patients to United Network for Organ Sharing ( UNOS) 1A-status during the holidays. Whether more transplants actually occur during holidays is unknown. Methods We assessed rates of single-organ heart transplantation from 2001 to 2010 for recipients age ≥18 yr using the UNOS database. Patients were stratified by transplantation during holiday (±3 d, n = 2375) and non-holiday periods (n = 16 112). Holidays included Easter/Spring break, Memorial Day, July 4th, Labor Day, Thanksgiving, and Christmas/New Years (winter holidays). Secondary analysis assessing transplant rates across seasons was also completed. Results Donor and recipient characteristics were similar between groups. Compared with non-holidays, July 4th had higher transplant rates (5.69 vs. 5.09 transplants/d, p = 0.03) while the winter holiday had lower transplant rates (4.50 vs. 5.09 transplants/d, p < 0.01). There was a trend toward lower transplant rates for all holidays compared with non-holidays (p = 0.06). Transplant rates were significantly different across seasons with greater rates in spring and summer (p < 0.01). Conclusion Heart transplant rates were higher during the July 4th and lower during the winter holidays. Although there was a higher likelihood of transplantation during the spring and summer seasons, upgrading patients to 1A status during most holidays may not improve their chances for transplantation. [ABSTRACT FROM AUTHOR]

Sirolimus is used in cardiac transplant recipients to prevent rejection, progression of cardiac allograft vasculopathy, and renal dysfunction. However, sirolimus has many potential side effects and its tolerability when used outside of clinical trials is not well established. We describe a decade of experience with sirolimus in cardiac transplant recipients at our institution. We retrospectively reviewed records of all adult cardiac transplant recipients living between September 1999 and February 2010 (n = 329) and identified 67 patients (20%) who received sirolimus. The indications for sirolimus were cardiac allograft vasculopathy (67%), renal dysfunction (25%), rejection (4%), and intolerability of tacrolimus (3%). One-third of patients discontinued sirolimus at a median (25th, 75th percentiles) of 0.9 (0.2, 1.6) yr of duration. Over 70% of subjects experienced an adverse event attributed to sirolimus. Adverse events were associated with higher average sirolimus levels (9.1 ng/mL vs. 7.1 ng/mL, p = 0.004). We conclude that sirolimus is frequently used in cardiac transplant recipients (20%) and commonly causes side effects, often necessitating discontinuation. Higher average sirolimus levels were associated with adverse events, suggesting that tolerability may improve if levels are maintained within the lower end of the current therapeutic range; however, the improvement in tolerability would need to be balanced with the potential for decreased efficacy. [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]

Sirolimus is an immunosuppressive agent increasingly used in cardiac transplant recipients in the setting of allograft vasculopathy or worsening renal function. Recently, sirolimus has been associated with increased risk of venous thromboembolism ( VTE) in lung transplant recipients. To investigate whether this association is also present in cardiac transplant recipients, we retrospectively reviewed the charts of 67 cardiac transplant recipients whose immunosuppressive regimen included sirolimus and 134 matched cardiac transplant recipients whose regimen did not include sirolimus. Rates of VTE were compared. Multivariable Cox proportional hazards models tested the association of sirolimus use with VTE. A higher incidence of VTE was seen in patients treated with vs. without sirolimus (8/67 [12%] vs. 9/134 [7%], log-rank statistic: 4.66, p = 0.03). Lower body mass index ( BMI) and total cholesterol levels were also associated with VTE (p < 0.05). The association of sirolimus with VTE persisted when adjusting for BMI (hazard ratio [95% confidence interval]: 2.96 [1.13, 7.75], p = 0.03) but not when adjusting for total cholesterol (p = 0.08). These data suggest that sirolimus is associated with an increased risk of VTE in cardiac transplant recipients, a risk possibly mediated through comorbid conditions. Larger, more conclusive studies are needed. Until such studies are completed, a heightened level of awareness for VTE in cardiac transplant recipients treated with sirolimus appears warranted. [ABSTRACT FROM AUTHOR]

Clinician counseling is a catalyst for lifestyle modification in obesity. Unfortunately, clinicians do not appropriately counsel all obese patients about lifestyle modification. The extent of disparities in clinician counseling is not well understood. Obese participants (BMI ≥30 kg/m2, N = 2097) in the Dallas Heart Study (DHS), a probability-based sample of Dallas County residents ages 18-65, were surveyed regarding health-care utilization and lifestyle counseling over the year prior to DHS enrollment. Health-care utilization and counseling were compared between obese participants across three categories based on the presence of 0, 1, or 2+ of the following cardiovascular (CV) risk factors: hypertension, hypercholesterolemia, or diabetes. Logistic regression modeling was used to determine likelihood of counseling in those with 0 vs. 1+ CV risk factors, stratified by race, adjusting for age, sex, insurance status, and education. Among obese subjects who sought medical care, those with 0 CV risk factors, compared to those with 1 or 2+ CV risk factors, were less likely to report counseling about losing weight (41% vs. 67% vs. 87%, P trend <0.001), dietary changes (44% vs. 71% vs. 85%, P trend <0.001), and physical activity (46% vs. 71% vs. 86%, P trend <0.001). Blacks and Hispanics without CV risk factors had a lower odds of receiving counseling than whites without risk factors on weight loss (adjusted odds ratio (OR), 95% confidence interval (CI) for nonwhites 0.19, [0.13-0.28], whites 0.48, [0.26-0.87]); dietary changes (nonwhites 0.19, [0.13-0.27], whites 0.37, [0.21-0.64]); and physical activity (nonwhites 0.22, [0.16-0.32], whites 0.32, [0.18-0.57]). Lifestyle counseling rates by clinicians are suboptimal among obese patients without CV risk factors, especially blacks and Hispanics. Systematic education about and application of lifestyle interventions could capitalize on opportunities for primary CV risk prevention. [ABSTRACT FROM AUTHOR]