Diet in Food Insecurity: A Mediator of Metabolic Health?

Objective: Food insecurity (FI) is associated with poor metabolic health. It is assumed that energy intake and diet quality underlie this association. We tested the hypothesis that dietary factors (quantity and quality) mediate the association of FI with excess weight, waist circumference and glycemic control [glycohemoglobin (A1C)]. Methods: A mediation analysis was performed on data from the National Health And Nutrition Examination Survey using FI as an independent variable; body mass index (BMI), waist circumference, and A1C as metabolic outcome variables and total energy intake, macronutrients, and diet quality measured by the Healthy Eating Index-2015 (HEI-2015) as potential mediators. Results: Despite a greater prevalence of obesity in participants experiencing FI, daily reported energy intake was similar in food-secure and -insecure subjects. In adjusted analyses of the overall cohort, none of the examined dietary factors mediated associations between FI and metabolic outcomes. In race-stratified analyses, total sugar consumption was a partial mediator of BMI in non-Hispanic Whites, while diet quality measures (HEI-2015 total score and added sugar subscore) were partial mediators of waist circumference and BMI, respectively, for those in the "other" ethnic group. Conclusion: Dietary factors are not the main factors underlying the association of FI with metabolic health. Future studies should investigate whether other social determinants of health commonly present in the context of FI play a role in this association.

E-value: a superior alternative to P-value and its adjustments in DNA methylation studies.

DNA methylation plays a crucial role in transcriptional regulation. Reduced representation bisulfite sequencing (RRBS) is a technique of increasing use for analyzing genome-wide methylation profiles. Many computational tools such as Metilene, MethylKit, BiSeq and DMRfinder have been developed to use RRBS data for the detection of the differentially methylated regions (DMRs) potentially involved in epigenetic regulations of gene expression. For DMR detection tools, as for countless other medical applications, P-values and their adjustments are among the most standard reporting statistics used to assess the statistical significance of biological findings. However, P-values are coming under increasing criticism relating to their questionable accuracy and relatively high levels of false positive or negative indications. Here, we propose a method to calculate E-values, as likelihood ratios falling into the null hypothesis over the entire parameter space, for DMR detection in RRBS data. We also provide the R package 'metevalue' as a user-friendly interface to implement E-value calculations into various DMR detection tools. To evaluate the performance of E-values, we generated various RRBS benchmarking datasets using our simulator 'RRBSsim' with eight samples in each experimental group. Our comprehensive benchmarking analyses showed that using E-values not only significantly improved accuracy, area under ROC curve and power, over that of P-values or adjusted P-values, but also reduced false discovery rates and type I errors. In applications using real RRBS data of CRL rats and a clinical trial on low-salt diet, the use of E-values detected biologically more relevant DMRs and also improved the negative association between DNA methylation and gene expression.

Wide Variability in Catecholamine Levels From Adrenal Venous Sampling in Primary Aldosteronism.

INTRODUCTION: While adrenal venous sampling (AVS) differentiates between the unilateral and bilateral disease in patients with primary aldosteronism (PA), it is unknown if AVS can determine laterality of pheochromocytoma in patients with bilateral adrenal masses. This study analyzes adrenal vein (AV) epinephrine and norepinephrine levels in nonpheochromocytoma patients to determine the "normal" range. MATERIALS AND METHODS: We reviewed patients who underwent AVS for PA between 2009 and 2019 at a single institution; pheochromocytoma was excluded. Aldosterone, cortisol, epinephrine, and norepinephrine levels were obtained from the inferior vena cava (IVC), left adrenal vein (LAV), and right adrenal vein (RAV). Successful AV cannulation was defined by an AV/IVC cortisol ratio of ≥3:1 or an AV epinephrine level ≥364 pg/mL. Plasma measurements (pg/mL) are median values with interquartile ranges; normal ranges for epinephrine and norepinephrine are 10-200 pg/mL and 80-520 pg/mL, respectively. RESULTS: AVS was performed in 172 patients in 405 AVs (173 LAV and 232 RAV). Median epinephrine levels were IVC = 19 (14 and 34), LAV = 3811 (1870 and 6915), and RAV = 2897 (1500 and 5288). Median norepinephrine levels were IVC = 325 (186 and 479), LAV = 1450 (896 and 2050), and RAV = 786 (436 and 1582). There was a difference between LAV and RAV epinephrine levels (P = 0.024) and between LAV and RAV norepinephrine (P = 0.002) levels. CONCLUSIONS: This extensive experience with AVS demonstrated a wide range of "normal" AV catecholamine levels in patients without pheochromocytoma, which suggests that the utility of AVS to determine disease laterality in patients with pheochromocytoma and bilateral adrenal nodules is likely to be limited.

Insulin Prevents Hypercholesterolemia by Suppressing 12α-Hydroxylated Bile Acids.

BACKGROUND: The risk of cardiovascular disease in type 1 diabetes remains extremely high, despite marked advances in blood glucose control and even the widespread use of cholesterol synthesis inhibitors. Thus, a deeper understanding of insulin regulation of cholesterol metabolism, and its disruption in type 1 diabetes, could reveal better treatment strategies. METHODS: To define the mechanisms by which insulin controls plasma cholesterol levels, we knocked down the insulin receptor, FoxO1, and the key bile acid synthesis enzyme, CYP8B1. We measured bile acid composition, cholesterol absorption, and plasma cholesterol. In parallel, we measured markers of cholesterol absorption and synthesis in humans with type 1 diabetes treated with ezetimibe and simvastatin in a double-blind crossover study. RESULTS: Mice with hepatic deletion of the insulin receptor showed marked increases in 12α-hydroxylated bile acids, cholesterol absorption, and plasma cholesterol. This phenotype was entirely reversed by hepatic deletion of FoxO1. FoxO1 is inhibited by insulin and required for the production of 12α-hydroxylated bile acids, which promote intestinal cholesterol absorption and suppress hepatic cholesterol synthesis. Knockdown of Cyp8b1 normalized 12α-hydroxylated bile acid levels and completely prevented hypercholesterolemia in mice with hepatic deletion of the insulin receptor (n=5-30), as well as mouse models of type 1 diabetes (n=5-22). In parallel, the cholesterol absorption inhibitor, ezetimibe, normalized cholesterol absorption and low-density lipoprotein cholesterol in patients with type 1 diabetes as well as, or better than, the cholesterol synthesis inhibitor, simvastatin (n=20). CONCLUSIONS: Insulin, by inhibiting FoxO1 in the liver, reduces 12α-hydroxylated bile acids, cholesterol absorption, and plasma cholesterol levels. Thus, type 1 diabetes leads to a unique set of derangements in cholesterol metabolism, with increased absorption rather than synthesis. These derangements are reversed by ezetimibe, but not statins, which are currently the first line of lipid-lowering treatment in type 1 diabetes. Taken together, these data suggest that a personalized approach to lipid lowering in type 1 diabetes may be more effective and highlight the need for further studies specifically in this group of patients.

Unique Associations of DNA Methylation Regions With 24-Hour Blood Pressure Phenotypes in Black Participants.

BACKGROUND: Epigenetic marks (eg, DNA methylation) may capture the effect of gene-environment interactions. DNA methylation is involved in blood pressure (BP) regulation and hypertension development; however, no studies have evaluated its relationship with 24-hour BP phenotypes (daytime, nighttime, and 24-hour average BPs). METHODS: We examined the association of whole blood DNA methylation with 24-hour BP phenotypes and clinic BPs in a discovery cohort of 281 Blacks participants using reduced representation bisulfite sequencing. We developed a deep and region-specific methylation sequencing method, Bisulfite ULtrapLEx Targeted Sequencing and utilized it to validate our findings in a separate validation cohort (n=117). RESULTS: Analysis of 38 215 DNA methylation regions (MRs), derived from 1 549 368 CpG sites across the genome, identified up to 72 regions that were significantly associated with 24-hour BP phenotypes. No MR was significantly associated with clinic BP. Two to 3 MRs were significantly associated with various 24-hour BP phenotypes after adjustment for age, sex, and body mass index. Together, these MRs explained up to 16.5% of the variance of 24-hour average BP, while age, sex, and BMI explained up to 11.0% of the variance. Analysis of one of the MRs in an independent cohort using Bisulfite ULtrapLEx Targeted Sequencing confirmed its association with 24-hour average BP phenotype. CONCLUSIONS: We identified several MRs that explain a substantial portion of variances in 24-hour BP phenotypes, which might be excellent markers of cumulative effect of factors influencing 24-hour BP levels. The Bisulfite ULtrapLEx Targeted Sequencing workflow has potential to be suitable for clinical testing and population screenings on a large scale.

Utility of Epinephrine Levels in Determining Adrenal Vein Cannulation During Adrenal Venous Sampling for Primary Aldosteronism.

OBJECTIVE: In patients with primary aldosteronism, adrenal venous sampling (AVS) is performed to determine the presence of unilateral or bilateral adrenal disease. During AVS, verification of catheter positioning within the left adrenal vein (AV) and the right AV by comparison of AV and inferior vena cava (IVC) cortisol levels can be variable. The objective of this study was to determine the utility of AV epinephrine levels in assessing successful AV cannulation. METHODS: This was a single institution, retrospective review of patients who underwent AVS with cosyntropin stimulation for primary aldosteronism between 2009 and 2018. Successful cannulation of the AV was defined by an AV/IVC cortisol ratio selectivity index (SI) ≥3:1. Epinephrine thresholds to predict catheter placement in the AV were determined using logistic regression. The calculated epinephrine thresholds were compared with previously published thresholds. RESULTS: AVS was performed on 101 consecutive patients and, based on the SI, successful cannulation of the left AV and right AV occurred in 98 (97%) and 91(90%) patients, respectively. The calculated optimal epinephrine threshold to predict AV cannulation was 364 pg/mL (sensitivity, 92.1%; specificity, 94.6%) and the calculated optimal AV/IVC epinephrine ratio threshold was 27.4, (sensitivity, 92.1%; specificity, 91.3%). Among the 14 patients with failed AV cannulation, 3 patients would have been considered to have successful AVS using AV epinephrine levels >364 pg/mL and AV/IVC epinephrine ratio >27.4 thresholds. CONCLUSION: Obtaining 2 right AV samples routinely as well as AV and IVC epinephrine levels during AVS could prevent unnecessary repeat AVS in patients with failed AV cannulation based on cortisol-based SI <3:1.

Dietary supplements and alternative therapies for obesity: A Perspective from The Obesity Society's Clinical Committee.

In this Perspective Statement from The Obesity Society, the Clinical Committee discusses the use of weight loss supplements in the United States and the lack of regulatory oversight and rigorous testing of their efficacy and safety. A number of products and services claiming to promote weight loss are directly marketed to individuals with obesity and those wanting to lose weight. These products are not regulated as "drugs" by the Federal Drug Administration but, rather, are treated as dietary supplements if ingredients are "generally regarded as safe," requiring little or no testing to show efficacy or safety. Health care providers should be aware of the lack of evidence and deficiencies in regulatory oversight of dietary supplements marketed for weight loss. Regulatory authorities should protect consumers by ensuring accurate and safe marketing claims and preventing promotion of unproven and potentially unsafe products and claims.

A Systematic Review of Dietary Supplements and Alternative Therapies for Weight Loss.

OBJECTIVE: Dietary supplements and alternative therapies are commercialized as a panacea for obesity/weight gain as a result of the minimal regulatory requirements in demonstrating efficacy. These products may indirectly undermine the value of guideline-driven obesity treatments. Included in this study is a systematic review of the literature of purported dietary supplements and alternative therapies for weight loss. METHODS: A systematic review was conducted to evaluate the efficacy of dietary supplements and alternative therapies for weight loss in participants aged ≥18 years. Searches of Medline (PubMed), Cochrane Library, Web of Science, CINAHL, and Embase (Ovid) were conducted. Risk of bias and results were summarized qualitatively. RESULTS: Of the 20,504 citations retrieved in the database search, 1,743 full-text articles were reviewed, 315 of which were randomized controlled trials evaluating the efficacy of 14 purported dietary supplements, therapies, or a combination thereof. Risk of bias and sufficiency of data varied widely. Few studies (n = 52 [16.5%]) were classified as low risk and sufficient to support efficacy. Of these, only 16 (31%) noted significant pre/post intergroup differences in weight (range: 0.3-4.93 kg). CONCLUSIONS: Dietary supplements and alternative therapies for weight loss have a limited high-quality evidence base of efficacy. Practitioners and patients should be aware of the scientific evidence of claims before recommending use.

Dietary Sodium Restriction Results in Tissue-Specific Changes in DNA Methylation in Humans.

[Figure: see text].

Team Science: American Heart Association's Hypertension Strategically Focused Research Network Experience.

In 2015, the American Heart Association awarded 4-year funding for a Strategically Focused Research Network focused on hypertension composed of 4 Centers: Cincinnati Children's Hospital, Medical College of Wisconsin, University of Alabama at Birmingham, and University of Iowa. Each center proposed 3 integrated (basic, clinical, and population science) projects around a single area of focus relevant to hypertension. Along with scientific progress, the American Heart Association put a significant emphasis on training of next-generation hypertension researchers by sponsoring 3 postdoctoral fellows per center over 4 years. With the center projects being spread across the continuum of basic, clinical, and population sciences, postdoctoral fellows were expected to garner experience in various types of research methodologies. The American Heart Association also provided a number of leadership development opportunities for fellows and investigators in these centers. In addition, collaboration was highly encouraged among the centers (both within and outside the network) with the American Heart Association providing multiple opportunities for meeting and expanding associations. The area of focus for the Cincinnati Children's Hospital Center was hypertension and target organ damage in children utilizing ambulatory blood pressure measurements. The Medical College of Wisconsin Center focused on epigenetic modifications and their role in pathogenesis of hypertension using human and animal studies. The University of Alabama at Birmingham Center's areas of research were diurnal blood pressure patterns and clock genes. The University of Iowa Center evaluated copeptin as a possible early biomarker for preeclampsia and vascular endothelial function during pregnancy. In this review, challenges faced and successes achieved by the investigators of each of the centers are presented.

Twenty-four-hour versus clinic blood pressure levels as predictors of long-term cardiovascular and renal disease outcomes among African Americans.

In Caucasian and Asian populations, evidence suggests that 24-h blood pressures (BP) are more predictive of long-term cardiovascular events than clinic BP. However, few long-term studies have evaluated the predictive value of 24-h BP phenotypes (24-h, daytime, nighttime) among African Americans (AA). The purpose of this study is to evaluate the added value of 24-h BP phenotypes compared to clinic BP in predicting the subsequent fatal and non-fatal cardiovascular/renal disease events in AA subjects. AA subjects (n = 270) were initially studied between 1994 and 2006 and standardized clinic BP measurements were obtained during screening procedures for a 3-day inpatient clinical study during which 24-h BP measurements were obtained. To assess the subsequent incidence of cardiovascular and renal disease events, follow-up information was obtained and confirmed by review of paper and electronic medical records between 2015 and 2017. During a mean follow-up of 14 ± 4 years, 50 subjects had one or more fatal or non-fatal cardiovascular/renal disease events. After adjustment for covariates, clinic systolic and diastolic BP were strongly associated with cardiovascular/renal disease events and all-cause mortality (p < 0.0001). Twenty-four-hour BP phenotypes conferred a small incremental advantage over clinic BP in predicting cardiovascular/renal events, which was limited to making a difference of one predicted event in 250-1,000 predictions depending on the 24-h BP phenotype. Nocturnal BP was no more predictive than the other 24-h BP phenotypes. In AA, 24-h BP monitoring provides limited added value as a predictor of cardiovascular/renal disease events. Larger studies are needed in AA to confirm these findings.

Weight History in Clinical Practice: The State of the Science and Future Directions.

Eliciting a weight history can provide clinically important information to aid in treatment decision-making. This view is consistent with the life course perspective of obesity and the aim of patient-centered care, one of six domains of health care quality. However, thus far, the value and practicality of including a weight history in the clinical assessment and treatment of patients with obesity have not been systematically explored. For these reasons, the Clinical Committee of The Obesity Society established a task force to review and assess the available evidence to address five key questions. It is concluded that weight history is an essential component of the medical history for patients presenting with overweight or obesity, and there are strong and emerging data that demonstrate the importance of life stage, duration of exposure to obesity, maximum BMI, and group-based trajectory modeling in predicting risk for increased morbidity and mortality. Consideration of these and other patient-specific factors may improve risk stratification and clinical decision-making for screening, counseling, and management. Recommendations are provided for the key elements that should be included in a weight history, and several needs for future clinical research are outlined.

Epigenetic Modifications in T Cells: The Role of DNA Methylation in Salt-Sensitive Hypertension.

The SS (Dahl salt sensitive) rat is an established model of hypertension and renal damage that is accompanied with immune system activation in response to a high-salt diet. Investigations into the effects of sodium-independent and dependent components of the diet were shown to affect the disease phenotype with SS/MCW (JrHsdMcwi) rats maintained on a purified diet (AIN-76A) presenting with a more severe phenotype relative to grain-fed SS/CRL (JrHsdMcwiCrl) rats. Since contributions of the immune system, environment, and diet are documented to alter this phenotype, this present study examined the epigenetic profile of T cells isolated from the periphery and the kidney from these colonies. T cells isolated from kidneys of the 2 colonies revealed that transcriptomic and functional differences may contribute to the susceptibility of hypertension and renal damage. In response to high-salt challenge, the methylome of T cells isolated from the kidney of SS/MCW exhibit a significant increase in differentially methylated regions with a preference for hypermethylation compared with the SS/CRL kidney T cells. Circulating T cells exhibited similar methylation profiles between colonies. Utilizing transcriptomic data from T cells isolated from the same animals upon which the DNA methylation analysis was performed, a predominant negative correlation was observed between gene expression and DNA methylation in all groups. Lastly, inhibition of DNA methyltransferases blunted salt-induced hypertension and renal damage in the SS/MCW rats providing a functional role for methylation. This study demonstrated the influence of epigenetic modifications to immune cell function, highlighting the need for further investigations.

Dietary Effects on Dahl Salt-Sensitive Hypertension, Renal Damage, and the T Lymphocyte Transcriptome.

The Dahl salt-sensitive (SS) rat is an established model of SS hypertension and renal damage. In addition to salt, other dietary components were shown to be important determinants of hypertension in SS rats. With previous work eliminating the involvement of genetic differences, grain-fed SS rats from Charles River Laboratories (SS/CRL; 5L2F/5L79) were less susceptible to salt-induced hypertension and renal damage compared with purified diet-fed SS rats bred at the Medical College of Wisconsin (SS/MCW; 0.4% NaCl, AIN-76A). With the known role of immunity in hypertension, the present study characterized the immune cells infiltrating SS/MCW and SS/CRL kidneys via flow cytometry and RNA sequencing in T-cells isolated from the blood and kidneys of rats maintained on their respective parental diet or on 3 weeks of high salt (4.0% NaCl, AIN-76A). SS/CRL rats were protected from salt-induced hypertension (116.5±1.2 versus 141.9±14.4 mm Hg), albuminuria (21.7±3.5 versus 162.9±22.2 mg/d), and renal immune cell infiltration compared with SS/MCW. RNA-seq revealed >50% of all annotated genes in the entire transcriptome to be significantly differentially expressed in T-cells isolated from blood versus kidney, regardless of colony or chow. Pathway analysis of significantly differentially expressed genes between low and high salt conditions demonstrated changes related to inflammation in SS/MCW renal T-cells compared with metabolism-related pathways in SS/CRL renal T-cells. These functional and transcriptomic T-cell differences between SS/MCW and SS/CRL show that dietary components in addition to salt may influence immunity and the infiltration of immune cells into the kidney, ultimately impacting susceptibility to salt-induced hypertension and renal damage.

Do we need race-specific resting metabolic rate prediction equations?

BACKGROUND: Resting metabolic rate (RMR) is a key determinant of daily caloric needs. Respirometry, a form of indirect calorimetry (IC), is considered one of the most accurate methods to measure RMR in clinical and research settings. It is impractical to measure RMR by IC in routine clinical practice; therefore, several formulas are used to predict RMR. In this study, we sought to determine the accuracy of these formulas in determining RMR and assess additional factors that may determine RMR. METHODS: We measured RMR in 114 subjects (67% female, 30% African American [AA]) using IC. Along with standard anthropometrics, dual-energy X-ray absorptiometry was used to obtain fat-free mass(FFM) and total fat mass. Measured RMR (mRMR) by respirometry was compared with predicted RMR (pRMR) generated by Mifflin-St.Joer, Cunningham, and Harris-Benedict (HB) equations. Linear regression models were used to determine factors affecting mRMR. RESULTS: Mean age, BMI, and mRMR of subjects were 46 ± 16 years (mean ± SD), 35 ± 10 kg/m2, and 1658 ± 391 kcal/day, respectively. After adjusting for age, gender, and anthropometrics, the two largest predictors of mRMR were race (p < 0.0001) and FFM (p < 0.0001). For every kg increase in FFM, RMR increased by 28 kcal/day (p < 0.0001). AA race was associated with 144 kcal/day (p < 0.0001) decrease in mRMR. The impact of race on mRMR was mitigated by adding in truncal FFM to the model. When using only clinically measured variables to predict mRMR, we found race, hip circumference, age, gender, and weight to be significant predictors of mRMR (p < 0.005). Mifflin-St.Joer and HB equations that use just age, gender, height, and weight overestimated kcal expenditure in AA by 138 ± 148 and 242 ± 164 (p < 0.0001), respectively. CONCLUSION: We found that formulas utilizing height, weight, gender, and age systematically overestimate mRMR and hence predict higher calorie needs among AA. The lower mRMR in AA could be related to truncal fat-free mass representing the activity of metabolically active intraabdominal organs.

Effect of adiposity on tissue-specific adiponectin secretion.

Circulating adiponectin levels are lower in individuals with increased BMI and central adiposity. However, they are paradoxically higher in those with peripheral adiposity. We hypothesized that adiponectin secretion from central and peripheral adipose tissue depots may be associated with adiposity levels and its distribution. A total of 55 subjects (69% women) undergoing elective abdominal surgery (mean age: 53 ± 13 years) were recruited. Health history, anthropometrics, and cardiovascular disease risk factor measurements were obtained. Subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) samples were obtained and cultured. Media was collected after 24hr and adiponectin released into the medium was measured using ELISA. We found that mean adiponectin levels from SAT and VAT in all subjects were 17.14±15.27 vs. 15.21±14.28 pg/ml/mg of tissue respectively (p = ns). However, adiponectin secretion from VAT correlated negatively with BMI (r = -0.31, p = 0.01), whereas there was no relationship with SAT (r = 0.08 p = 0.61). Similarly, waist circumference and estimated VAT percentage were both negatively correlated with VAT secretion of adiponectin (r = -0.35, p = 0.01 and r = -0.36, p = 0.02 respectively). These negative correlations were significant only in women on gender-stratified analyses. Adiponectin secretion from VAT decreases with increases in adiposity, while SAT secretion remains unchanged, especially in women. This observation may explain lower circulating adiponectin levels in individuals with central obesity. Further studies are needed to explore the mechanism behind this discrepant adiponectin secretion from SAT and VAT with increases in BMI, particularly among women.

Stability of global methylation profiles of whole blood and extracted DNA under different storage durations and conditions.

AIM: To test whether DNA samples stored for a prolonged period (20 years) under various storage conditions could be used for comparative methylation studies using reduced representation bisulfite sequencing. PATIENTS & METHODS: Five groups of human blood DNA samples (n = 5-6/group) were compared. The groupings were based on the anticoagulant used and storage temperature and duration. RESULTS: Methylation profiles of defined genomic regions in the DNA or blood samples archived for 20 years were similar across all storage temperatures, including 4°C. The level of intersample similarity in archived samples was not significantly different than that in recently collected samples. CONCLUSION: Archived samples, including DNA stored at 4°C for 20 years, are suitable for comparative studies of DNA methylation.

Epidemiology of Obesity and Pharmacologic Treatment Options.

Prevalence of obesity and its related morbidity have increased to alarming levels in adults and children in the United States and globally. Weight loss results in improvement of much of the obesity-related morbidity. Lifestyle changes such as dietary modifications, increased physical activity, and behavioral therapy form the crux of weight management. However, many individuals need additional assistance (pharmacologic or surgical) to initiate or sustain weight loss. Pharmacologic therapy consists of a number of agents that work by decreasing appetite, gastric emptying, or nutrient absorption or by increasing satiety. Five classes of drug are currently approved for adults, including sympathomimetics (with and without an antiepileptic agent topiramate), gastrointestinal lipase inhibitors, serotonin agonists, glucagon-like peptide 1 agonists, and antidepressant/opioid antagonist combination. Pharmacologic options for children with obesity are minimal (lipase inhibitor orlistat is the only approved medication for children aged >12 years); however, all adult medications are approved by the Food and Drug Administration for children aged >16 years old. While side effect profiles of these medications are far superior to older medications, their use is limited by lack of long-term cardiovascular safety data, costs of medications and variable insurance coverages, and the need for continued usage for sustainable benefits. Weight loss medications may induce complacence, on part of both the patient and the provider, regarding lifestyle modifications, without which the drug therapy is almost certain to be of minimal benefit. Several novel drugs are in the pipeline targeting brown fat, energy expenditure, appetite suppression, and satiety.

Effect of gender and adiposity on in vivo vascular function in young African Americans.

The relationship between obesity and high blood pressure is not as strong among African Americans (AA) as compared to Caucasians. We designed the current study to determine the effect of adiposity on vascular endothelial function (a harbinger of hypertension) among young healthy AA without additional cardiovascular disease risk factors. A total of 108 AA subjects (46 women) between the ages of 18 and 45 years were recruited. All the subjects were normotensive, nonsmokers, and normoglycemic. Anthropometric and cardiovascular disease risk factor measurements (lipid, insulin resistance, and inflammatory markers) were obtained. Vascular endothelial function was measured by brachial artery flow-mediated dilation (FMD). Adiposity distribution was measured by using magnetic resonance imaging scan. There were no gender differences in age and levels of blood pressure, lipids, insulin resistance, and inflammatory markers. Women had higher total body fat percentage and higher peripheral adiposity compared to men. We observed that total and central adiposity did not correlate significantly with brachial artery FMD in women (r = -0.12 and r = 0.23, respectively; P = NS). However, in men, waist circumference was positively associated with FMD (r = 0.3, P ≤ .05). Hyperemic flow was negatively correlated significantly with total and central adiposity in men (r = -0.34 and r = -0.48, respectively; P < .05), but not in women (r = -0.26 and r = 0.03, respectively; P = NS). Our study suggests that increased adiposity may pose greater risk to AA men compared to AA women by adversely affecting resistance vessel function (as measured by hyperemic flow). Larger studies are necessary to validate these findings.