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Heidi J Silver1, E Brian Welch2, Malcolm J Avison2, Kevin D Niswender1,31Department of Medicine, 2Department of Radiology and Radiological Sciences, Institute of Imaging Sciences, Vanderbilt University, Nashville, TN, USA; 3Tennessee Valley Healthcare System, Nashville, TN, USAAbstract: Obesity is a threat to public health worldwide primarily due to the comorbidities related to visceral adiposity, inflammation, and insulin resistance that increase risk for type 2 diabetes and cardiovascular disease. The translational research portfolio that originally described these risk factors was significantly enhanced by imaging techniques, such as dual-energy X-ray absorptiometry (DEXA), computed tomography (CT), and magnetic resonance imaging (MRI). In this article, we briefly review the important contributions of these techniques to understand the role of body composition in the pathogenesis of obesity-related complications. Notably, these imaging techniques have contributed greatly to recent findings identifying gender and racial differences in body composition and patterns of body composition change during weight loss. Although these techniques have the ability to generate good-quality body composition data, each possesses limitations. For example, DEXA is unable to differentiate type of fat, CT has better resolution but provides greater ionizing radiation exposure, and MRI tends to require longer imaging times and specialized equipment for acquisition and analysis. With the serious need for efficacious and cost-effective therapies to appropriately identify and treat at-risk obese individuals, there is greater need for translational tools that can further elucidate the interplay between body composition and the metabolic aberrations associated with obesity. In conclusion, we will offer our perspective on the evolution toward an ideal imaging method for body composition assessment in obesity and weight loss, and the challenges remaining to achieve this goal.Keywords: obesity, imaging, body composition, visceral fat

Background: Persons with HIV (PWH) on contemporary antiretroviral therapy (ART) are at elevated risk for developing age-related cardiometabolic diseases. We hypothesized that integrative analysis of cross-tissue, multimodal data from PWH could provide insight into molecular programming that defines cardiometabolic phenotypes in this high-risk group., Methods: We enrolled 93 PWH without diabetes who were virologically suppressed on contemporary ART and obtained measures of insulin resistance, glucose intolerance, and adiposity. We performed circulating lipidomics, proteomics, and metabolomics, as well as subcutaneous adipose tissue (SAT) bulk transcriptomics, and used multiomics factor analysis (MOFA) to perform integrative analyses of these datasets., Results: The median age was 43 years, median body mass index 30.8 kg/m2, 81% were male, and 56% were self-identified non-Hispanic White. We identified a specific MOFA factor associated with visceral adipose tissue volume (ρ = -0.43), homeostasis model assessment 2 insulin resistance score (ρ = -0.52), liver density (ρ = 0.43), and other cardiometabolic risk factors, which explained more variance in the SAT transcriptome and circulating lipidome compared with the circulating proteome and metabolome. Gene set enrichment analysis of this factor showed extracellular matrix and inflammatory pathways that primarily mapped to SAT myeloid cells and adipose progenitor cells using single-cell deconvolution. Lipidomic analysis showed that this factor was significantly enriched for triacylglycerol and diacylglycerol species., Conclusions: Our multiomic analysis demonstrated coordinated, multitissue molecular reprogramming in virologically suppressed PWH with elevated cardiometabolic disease risk. Longitudinal studies of PWH with assessments of adipose tissue and lipid handling are necessary to understand mechanisms of cardiometabolic disease in PWH. Clinical Trials Registration. NCT04451980., Competing Interests: Potential conflicts of interest. J. R. K serves as a consultant to Merck & Co, Gilead Sciences, Janssen Pharmaceuticals, and Theratechnologies; and receives grant support from Merck & Co and Gilead Sciences. R. S. has served as a consultant for Amgen and Cytokinetics; and is a coinventor on a patent for ex-RNAs signatures of cardiac remodeling and a pending patent on proteomic signatures of fitness and lung and liver diseases. A. S. P. has patents pending on proteomic signatures of fitness, lung, and liver disease. J. A. K. reports grants/contracts from Boehringer Ingelheim; and scientific advisory board membership at APIE Therapeutics and Arda Therapeutics. C. N. W. serves as a consultant to Merck & Co and Gilead Sciences; and receives grant support from Gilead Sciences. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Context: Cardiometabolic diseases are common in persons with HIV (PWH) on antiretroviral therapy (ART), which has been attributed to preferential lipid storage in visceral adipose tissue (VAT) compared with subcutaneous adipose tissue (SAT). However, the relationship of SAT-specific cellular and molecular programs with VAT volume is poorly understood in PWH., Objective: We characterized SAT cell-type specific composition and transcriptional programs that are associated with greater VAT volume in PWH on contemporary ART., Methods: We enrolled PWH on long-term ART with a spectrum of metabolic health. Ninety-two participants underwent SAT biopsy for bulk RNA sequencing and 43 had single-cell RNA sequencing. Computed tomography quantified VAT volume and insulin resistance was calculated using the Homeostasis Model Assessment 2 Insulin Resistance (HOMA2-IR)., Results: VAT volume was associated with HOMA2-IR (P < .001). Higher proportions of SAT intermediate macrophages (IMs), myofibroblasts, and MYOC+ fibroblasts were associated with greater VAT volume using partial Spearman's correlation adjusting for age, sex, and body mass index (r = 0.34-0.49, P < .05 for all). Whole SAT transcriptomics showed PWH with greater VAT volume have increased expression of extracellular matrix (ECM)- and inflammation-associated genes, and reduced expression of lipolysis- and fatty acid metabolism-associated genes., Conclusion: In PWH, greater VAT volume is associated with a higher proportion of SAT IMs and fibroblasts, and a SAT ECM and inflammatory transcriptome, which is similar to findings in HIV-negative persons with obesity. These data identify SAT cell-type specific changes associated with VAT volume in PWH that could underlie the high rates of cardiometabolic diseases in PWH, though additional longitudinal studies are needed to define directionality and mechanisms., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Objective: The objective of this study was to determine the unique clinical and cardiometabolic risk characteristics of weight-cyclers and identify differences between weight-cyclers and individuals with other weight-change trajectories., Methods: A deidentified database of 1,428,204 Vanderbilt University Medical Center patients from 1997 to 2020 was included based on having ≥5 years of recorded weights. Patients with a history of malignant neoplasm, bariatric surgery, implausible BMI (e.g., <15 or >80 kg/m 2 ), or missing documented height were excluded, yielding 83,261 participants categorized by weight trajectory, i.e., weight-stable, weight-gainer, weight-loser, or weight-cycler, based on criteria of ≥5% weight-change thresholds. Additionally, quartiles of average successive weight variability were evaluated to determine the effect of absolute differences among successive weight values., Results: Over half (55%) of participants were weight-cyclers, 23% were weight-gainers, 12% were weight-losers, and 10% were weight-stable over 5 years. Although baseline BMI did not differ among groups, weight-cyclers were more likely to have lower high-density lipoprotein cholesterol and higher blood glucose and triglyceride levels and to have been prescribed antihypertensive, dyslipidemia, and/or antidiabetic therapies. They were also younger and more likely to be smokers. Participants with the greatest weight variability (i.e., highest quartile of average successive weight variability) had higher cardiometabolic risk scores., Conclusions: Weight cycling was highly prevalent but yielded no meaningful overall change in body weight after 5 years. These findings support a paradigm shift in weight management in individuals with overweight/obesity toward reducing cardiometabolic risk with or without weight loss., (© 2024 The Author(s). Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)

Background: In the general population, it is established that adipose tissue depots pose various risks for cardiometabolic diseases. The interaction among obesity, HIV, and antiretroviral treatment promotes even greater risk for persons with HIV (PWH). As obesity is a heterogeneous condition, determining the specific obesity phenotypes present and their characteristics is critical to personalize care in PWH., Methods: Visceral, sarcopenic, myosteatotic, hepatosteatotic, and metabolically healthy obesity phenotypes were determined by pre-established cut points after segmentation of computed tomography scans at the L3 vertebra. Multivariable linear regression modeling included anthropometrics, clinical biomarkers, and inflammatory factors while controlling for age, sex, race, and body mass index (BMI)., Results: Of 187 PWH, 86% were male, and the mean ± SD age and BMI were 51.2 ± 12.3 years and 32.6 ± 6.3 kg/m 2 . Overall, 59% had visceral obesity, 11% sarcopenic obesity, 25% myosteatotic obesity, 9% hepatosteatotic obesity, and 32% metabolically healthy obesity. The strongest predictor of visceral obesity was an elevated triglyceride:high-density lipoprotein (HDL) ratio. Increased subcutaneous fat, waist circumference, and HDL cholesterol were predictors of sarcopenic obesity. Diabetes status and elevated interleukin 6, waist circumference, and HDL cholesterol predicted myosteatotic obesity. An increased CD4+ count and a decreased visceral:subcutaneous adipose tissue ratio predicted hepatosteatotic obesity, though accounting for only 28% of its variability. Participants with metabolically healthy obesity were on average 10 years younger, had higher HDL, lower triglyceride:HDL ratio, and reduced CD4+ counts., Conclusions: These findings show that discrete obesity phenotypes are highly prevalent in PWH and convey specific risk factors that measuring BMI alone does not capture. These clinically relevant findings can be used in risk stratification and optimization of personalized treatment regimens. This study is registered at ClinicalTrials.gov (NCT04451980)., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

Background and Aims: The cardiometabolic disease-associated metabolite, alpha-aminoadipic acid (2-AAA) is formed from the breakdown of the essential dietary amino acid lysine. However, it was not known whether elevated plasma levels of 2-AAA are related to dietary nutrient intake. We aimed to determine whether diet is a determinant of circulating 2-AAA in healthy individuals, and whether 2-AAA is altered in response to dietary modification., Methods and Results: We investigated the association between 2-AAA and dietary nutrient intake in a cross-sectional study of healthy individuals (N = 254). We then performed a randomized cross-over dietary intervention trial to investigate the effect of lysine supplementation (1 week) on 2-AAA in healthy individuals (N = 40). We further assessed the effect of a vegetarian diet on 2-AAA in a short-term (4-day) dietary intervention trial in healthy omnivorous women (N = 35). We found that self-reported dietary intake of animal products, including meat, poultry, and seafood, was associated with higher plasma 2-AAA cross-sectionally (P < 0.0001). Supplementary dietary lysine (5g/day) caused no significant increase in plasma 2-AAA; however, plasma 2-AAA was altered by general dietary modification. Further, plasma 2-AAA was significantly reduced by a short-term vegetarian diet (P = 0.003)., Conclusion: We identified associations between plasma 2-AAA and consumption of animal products, which were validated in a vegetarian dietary intervention trial, but not in a trial designed to specifically increase the 2-AAA amino acid precursor lysine. Further studies are warranted to investigate whether implementation of a vegetarian diet improves cardiometabolic risk in individuals with elevated 2-AAA., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Some studies comparing persons with and without type 2 diabetes (T2DM) show no difference in resting energy expenditure (REE). However, the degree of glycemic control may be a crucial factor in determining energy requirements. Few studies have employed the doubly labeled water (DLW) method in persons with T2DM to objectively measure daily energy expenditure., Aims: To determine relationships between glycemia, body composition, and energy expenditure in adults with obesity and T2DM. We hypothesized that worse hyperglycemia, insulin resistance, and beta cell function would associate with higher resting and total energy expenditure (TEE)., Methods: Two cohorts age 31-50 years were included: 78 with obesity and T2DM, 19 with normal weight and no chronic disease. Baseline data from clinical biomarkers, intravenous glucose tolerance tests, DXA and MRI for body composition, and dietary intakes were used in multivariable regression models to predict REE and TEE. Additionally, comparisons were made by categorizing participants as having controlled or uncontrolled glycemia based on glucose levels ≥175 mg/dL., Results: REE was higher in participants with T2DM by 534.08 ± 74.35 kcal/d (p < 0.001). Higher fasting glucose and HbA1C levels associated with higher TEE. Abdominal SAT and VAT were also predictors in regression models accounting for 76 % of the variance in REE and 89 % of TEE. Participants with uncontrolled glycemia had 22 % higher adipose/lean ratio, two-fold higher VAT/SAT ratio, 21 % higher HOMA-IR score, and worse beta cell function (mean difference in HOMA2-%β of 74.09 ± 14.01, p < 0.001) than those with controlled glycemia. Both REE and TEE were significantly higher in uncontrolled glycemia, difference in REE of 154.17 ± 96.28 kcals/day (p = 0.04) and difference in TEE of 480.64 ± 215.45 kcals/day (p = 0.03)., Conclusions: Poor beta cell function and uncontrolled glycemia associate with higher REE and TEE in persons with obesity and T2DM. This study is registered with clinicaltrials.gov identifier: NCT01239550., Competing Interests: Conflict of interest The authors report no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Metabolic effects of glucagon-like peptide 1 (GLP-1) receptor agonists are confounded by weight loss and not fully recapitulated by increasing endogenous GLP-1. We tested the hypothesis that GLP-1 receptor (GLP-1R) agonists exert weight loss-independent, GLP-1R-dependent effects that differ from effects of increasing endogenous GLP-1. Individuals with obesity and prediabetes were randomized to receive for 14 weeks the GLP-1R agonist liraglutide, a hypocaloric diet, or the dipeptidyl peptidase 4 (DPP-4) inhibitor sitagliptin. The GLP-1R antagonist exendin(9-39) and placebo were administered in a two-by-two crossover study during mixed-meal tests. Liraglutide and diet, but not sitagliptin, caused weight loss. Liraglutide improved insulin sensitivity measured by HOMA for insulin resistance (HOMA-IR), the updated HOMA model (HOMA2), and the Matsuda index after 2 weeks, prior to weight loss. Liraglutide decreased fasting and postprandial glucose levels, and decreased insulin, C-peptide, and fasting glucagon levels. In contrast, diet-induced weight loss improved insulin sensitivity by HOMA-IR and HOMA2, but not the Matsuda index, and did not decrease glucose levels. Sitagliptin increased endogenous GLP-1 and GIP values without altering insulin sensitivity or fasting glucose levels, but decreased postprandial glucose and glucagon levels. Notably, sitagliptin increased GIP without altering weight. Acute GLP-1R antagonism increased glucose levels in all groups, increased the Matsuda index and fasting glucagon level during liraglutide treatment, and increased endogenous GLP-1 values during liraglutide and sitagliptin treatments. Thus, liraglutide exerts rapid, weight loss-independent, GLP-1R-dependent effects on insulin sensitivity that are not achieved by increasing endogenous GLP-1., Article Highlights: Metabolic benefits of glucagon-like peptide 1 (GLP-1) receptor agonists are confounded by weight loss and are not fully achieved by increasing endogenous GLP-1 through dipeptidyl peptidase 4 (DPP-4) inhibition. We investigated weight loss-independent, GLP-1 receptor (GLP-1R)-dependent metabolic effects of liraglutide versus a hypocaloric diet or the DPP-4 inhibitor sitagliptin. GLP-1R antagonism with exendin(9-39) was used to assess GLP-1R-dependent effects during mixed meals. Liraglutide improved insulin sensitivity and decreased fasting and postprandial glucose prior to weight loss, and these benefits were reversed by exendin(9-39). GLP-1R agonists exert rapid, weight loss-independent, GLP-1R-dependent effects on insulin sensitivity not achieved by increasing endogenous GLP-1., (© 2023 by the American Diabetes Association.)

Metabolic syndrome (MetSx) and its chronic disease consequences are major public health concerns worldwide. Between-meal snacking may be a modifiable risk factor. We hypothesized that consuming tree nuts as snacks, versus typical carbohydrate snacks, would reduce risk for MetSx in young adults. A prospective, randomized, 16-week parallel-group diet intervention trial was conducted in 84 adults aged 22-36 with BMI 24.5 to 34.9 kg/m 2 and ≥1 MetSx clinical risk factor. Tree nuts snacks (TNsnack) were matched to carbohydrate snacks (CHOsnack) for energy (kcal), protein, fiber, and sodium content as part of a 7-day eucaloric menu. Difference in change between groups was tested by analysis of covariance using general linear models. Multivariable linear regression modeling assessed main effects of TNsnack treatment and interactions between TNsnack and sex on MetSx score. Age, BMI, and year of study enrollment were included variables. There was a main effect of TNsnack on reducing waist circumference in females (mean difference: -2.20 ± 0.73 cm, p = 0.004) and a trend toward reduced visceral fat (-5.27 ± 13.05 cm 2 , p = 0.06). TNsnack decreased blood insulin levels in males (-1.14 ± 1.41 mIU/L, p = 0.05) and multivariable modeling showed a main effect of TNsnack on insulin. Main effects of TNsnack on triglycerides and TG/HDL ratio were observed ( p = 0.04 for both) with TG/HDL ratio reduced ~11%. A main effect of TNsnack ( p = 0.04) and an interaction effect between TNsnack and sex ( p < 0.001) on total MetSx score yielded 67% reduced MetSx score in TNsnack females and 42% reduced MetSx score in TNsnack males. To our knowledge, this is the first randomized parallel-arm study to investigate cardiometabolic responses to TNsnacks versus typical CHOsnacks among young adults at risk of MetSx. Our study suggests daily tree nut consumption reduces MetSx risk by improving waist circumference, lipid biomarkers, and/or insulin sensitivity-without requiring caloric restriction.

Our recent study showed weight cycled mice have increased adipose mast cells compared to obese mice by single cell RNA-sequencing. Here, we aimed to confirm and elucidate these changes. Further analysis of our dataset showed that our initial mast cell cluster could subcluster into two unique populations: one with very high expression of classical mast cell markers and another with elevated lipid handling and antigen presentation genes. This new mast cell cluster accounted for most of the mast cells in the weight cycled group although it was not possible to detect the different populations by new studies with flow cytometry or Toluidine blue staining in mice, possibly due to a downregulation in classical mast cell genes. Interestingly, a pilot study in humans did suggest the existence of two mast cell populations in subcutaneous adipose tissue from obese women that appear similar to the murine populations detected by sequencing; one of which was significantly correlated with weight variance. Together, these data suggest that weight cycling may induce a unique population of mast cells similar to lipid associated macrophages. Future studies will focus on isolation of these cells to better determine their lineage, differentiation, and functional roles.

Introduction: Plasma levels of the metabolite alpha-aminoadipic acid (2-AAA) have been associated with risk of type 2 diabetes (T2D) and atherosclerosis. However, little is known about the relationship of 2-AAA to other cardiometabolic risk markers in pre-disease states, or in the setting of comorbid disease., Methods: We measured circulating 2-AAA using two methods in 1) a sample of 261 healthy individuals (2-AAA Study), and 2) in a sample of 134 persons comprising 110 individuals with treated HIV, with or without T2D, a population at high risk of metabolic disease and cardiovascular events despite suppression of circulating virus, and 24 individuals with T2D without HIV (HATIM Study). We examined associations between plasma 2-AAA and markers of cardiometabolic health within each cohort., Results and Discussion: We observed differences in 2-AAA by sex and race in both cohorts, with higher levels observed in men compared with women, and in Asian compared with Black or white individuals (P<0.05). There was no significant difference in 2-AAA by HIV status within individuals with T2D in the HATIM Study. We confirmed associations between 2-AAA and dyslipidemia in both cohorts, where high 2-AAA associated with low HDL cholesterol (P<0.001) and high triglycerides (P<0.05). As expected, within the cohort of people with HIV, 2-AAA was higher in the setting of T2D compared to pre-diabetes or normoglycemia (P<0.001). 2-AAA was positively associated with body mass index (BMI) in the 2-AAA Study, and with waist circumference and measures of visceral fat volume in HATIM (all P<0.05). Further, 2-AAA associated with increased liver fat in persons with HIV (P<0.001). Our study confirms 2-AAA as a marker of cardiometabolic risk in both healthy individuals and those at high cardiometabolic risk, reveals relationships with adiposity and hepatic steatosis, and highlights important differences by sex and race. Further studies are warranted to establish molecular mechanisms linking 2-AAA to disease in other high-risk populations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Desine, Gabriel, Smith, Antonetti, Wang, Calcutt, Doran, Silver, Nair, Terry, Carr, Linton, Brown, Koethe and Ferguson.)

Background & Aims: Sarcopenia has significant burden in cirrhosis and has been shown to worsen short-term post-liver transplantation (LT). This study aims to evaluate the long-term change in sarcopenia post-LT along with its associations and predictors., Methods: A retrospective study of adult patients who underwent LT at a tertiary centre between 1/1/2009 and 12/31/2018. Relevant demographic and clinical data were collected. Skeletal muscle index (SMI) was calculated using standard of care computerised tomography (CT) scans pre- and post-LT. Sarcopenia was defined using previously established cut-points. The primary outcome was SMI change post-LT and secondary outcome was post-LT mortality., Results: Out of 1165 patients, 401 met inclusion criteria (1,205 CT scans reviewed). The average age at transplant was 57 years; 63% were male. The average BMI was 28 kg/m 2 . Thirteen percent of females and 32% of males had sarcopenia pre-LT. Post-LT SMI declined by 4.7 cm 2 /m 2 in the first year then by 0.39 cm 2 /m 2 per year thereafter. Females had greater rate of decline in SMI after the first year compared with males (0.87 cm 2 /m 2 per year vs. 0.17 cm 2 /m 2 per year, respectively, p  = 0.02). Post-LT physical rehabilitation, infection, and readmissions were not associated with SMI trajectory. At 3 years post-LT, 31% of females and 48% of males had sarcopenia. Baseline sarcopenia was the only predictor of long-term post-LT sarcopenia on multivariable analysis, but it was not associated with mortality., Conclusions: Sarcopenia does not appear to resolve post-LT and likely worsens leading to nearly doubling its prevalence in those with long-term follow-up. Immediate post-LT physical rehabilitation was not associated with SMI trajectory in our cohort., Impact and Implications: The prevalence of sarcopenia is high among patients with cirrhosis; however, data are mixed on the impact of sarcopenia on post-liver transplant (LT) course and there have been no studies evaluating the long-term evolution of sarcopenia post-LT beyond 1 year. In this study, we analysed changes in muscle mass up to 3 years after transplant in 401 patients and found that sarcopenia did not resolve in most liver transplant recipients and skeletal muscle mass tended to worsen after transplant with the greatest decline in muscle mass in the first year post-LT. Interestingly, sarcopenia did not influence post-transplant outcomes. Future prospective studies are needed to further understand the natural course of sarcopenia post-LT to guide interventions aiming at reversing post-LT sarcopenia., Competing Interests: The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2023 The Author(s).)

Aims: To investigate the hypothesis that weight loss with the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide alone would lead to a greater reduction in the proportion of fat to lean tissue mass when compared to caloric restriction (CR) alone, as well as when compared to treatment with sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, that also enhances GLP-1 activity - to determine the independent effects of each treatment., Methods: A total of 88 adults with obesity and prediabetes were randomized to 14 weeks of intervention with CR (-390 kcal/d), liraglutide (1.8 mg/d), or the dipeptidyl peptidase-4 inhibitor sitagliptin (100 mg/d) as a weight-neutral comparator. Changes between groups in appetite and hunger ratings measured via visual analogue scales, dietary intakes, body weight, body composition via dual energy x-ray absorptiometry, and resting energy expenditure via indirect calorimetry were assessed using the Kruskal-Wallis test or Pearson's chi-squared test., Results: Weight loss ≥5% of baseline body weight occurred in 44% of participants in the CR group, 22% of the liraglutide group and 5% of the sitagliptin group (p = 0.02). The ratio of fat to lean mass decreased by 6.5% in the CR group, 2.2% in the liraglutide group, and 0% in the sitagliptin group (p = 0.02). Visceral fat reduced by 9.5% in the CR group, 4.8% in the liraglutide group, and 0% in the sitagliptin group (p = 0.04). A spontaneous reduction in dietary simple carbohydrates in the CR group was associated with improved homeostatic model assessment of insulin resistance score (HOMA-IR)., Conclusions: Although both liraglutide and CR are valuable strategies for cardiometabolic risk reduction, CR was associated with greater weight loss and more favourable improvements in body composition than treatment with liraglutide alone. Differences in the response to each of these interventions enables patients to be stratified to the most optimal intervention for their personal risk factors., (© 2023 John Wiley & Sons Ltd.)

Background: Many types of diet intervention can achieve negative energy balance and successful weight loss in persons with obesity. However, within any dietary strategy, there is large inter-individual variation in the weight loss response. The aim of this study is to determine factors that predict weight loss success for diet interventions that vary by macronutrient and caloric composition., Methods: Participants with BMI 30.0 to 49.9 kg/m 2 self-selected one of three diet intervention trials for weight loss: low carbohydrate (LOW CHO), low fat (LOW FAT), or low calorie (LOW KCAL). Multivariable regression models were developed to determine the significance of predictor demographic, body composition, metabolic, clinical, and dietary variables for each diet type., Results: Weight loss over 12-16 weeks averaging -5.1 ± 4.0 kg from baseline weight, p  < 0.001, was not significantly different among diet types. Several different factors were identified that account for the inter-individual variance in weight loss success. Regardless of diet type, the most robust predictor of weight loss success was completion of the intervention, accounting for 20-30% of the variance. Factors predicting diet intervention completion were age, physical activity level, blood leptin level, blood pressure, and the amount of weight loss occurring. Differences by diet type in cardiometabolic risk factor reduction were identified with LOW CHO decreasing glycemia/insulinemia factors, LOW FAT decreasing lipidemia factors, and LOW KCAL decreasing inflammatory factors., Conclusion: These data provide evidence to inform more precise and personalized approaches to diet intervention for weight loss and cardiometabolic health., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor GB declared a shared affiliation with the author HS at the time of review., (Copyright © 2023 Losavio, Keenan, Gollub and Silver.)

Plasma levels of the metabolite alpha-aminoadipic acid (2-AAA) have been associated with risk of type 2 diabetes (T2D) and atherosclerosis. However, little is known about the relationship of 2-AAA to other cardiometabolic risk markers in pre-disease states, or in the setting of comorbid disease. We measured circulating 2-AAA using two methods in 1) a sample of 261 healthy individuals (2-AAA Study), and 2) in a sample of 134 persons comprising 110 individuals with treated HIV, with or without T2D, a population at high risk of metabolic disease and cardiovascular events despite suppression of circulating virus, and 24 individuals with T2D without HIV (HATIM Study). We examined associations between plasma 2-AAA and markers of cardiometabolic health within each cohort. We observed differences in 2-AAA by sex and race in both cohorts, with higher levels observed in men compared with women, and in Asian compared with Black or white individuals (P<0.05). There was no significant difference in 2-AAA by HIV status within individuals with T2D in the HATIM Study. We confirmed associations between 2-AAA and dyslipidemia in both cohorts where high 2-AAA associated with low HDL cholesterol (P<0.001) and high triglycerides (P<0.05). As expected, within the cohort of people with HIV, 2-AAA was higher in the setting of T2D compared to pre-diabetes or normoglycemia (P<0.001). 2-AAA was positively associated with body mass index (BMI) in the 2-AAA Study, and with waist circumference and measures of visceral fat volume in HATIM (all P<0.05). Further, 2-AAA associated with increased liver fat in persons with HIV (P<0.001). Our study confirms 2-AAA as a marker of cardiometabolic risk in both healthy individuals and those at high cardiometabolic risk, reveals relationships with adiposity and hepatic steatosis, and highlights important differences by sex and race. Further studies are warranted to establish molecular mechanisms linking 2-AAA to disease in other high-risk populations.

Background and Aims: Computed tomography (CT) defined myosteatotic, sarcopenic, and visceral obesity are associated with adverse surgical outcomes and mortality in patients with malignancies. These occult conditions may also be widely prevalent in today's general surgery patients who tend to be overweight/obese. This study identified the predominant obesity phenotypes in 906 patients aged 18-85 years who were scheduled for laparoscopic resection for benign abdominal or colorectal disease at Vanderbilt University Medical Center between 2010 and 2017., Methods: Sex and body mass index (BMI) specific cut-points were used to identify myosteatotic, sarcopenic, and visceral obesity phenotype from abdominal CT scan morphometrics. Multivariable regression modeling determined relationships between sex, obesity phenotype, and postoperative outcomes., Results: The myosteatostic + sarcopenic obesity phenotype associated with longer surgery duration and increased the likelihood for major complication (OR 1.34, 95%CI 1.01-1.74) and ICU admission (OR 1.39, 95%CI 1.04-1.90). Having myosteatotic obesity doubled the likelihood for hospital stay >7 days and discharge to a nursing home (OR 2.11, 95%CI 1.43,3.11), increasing the likelihood for readmission within 90 days. Obesity was more prevalent in females, but myosteatotic, sarcopenic, and visceral obesity were more prevalent in males, regardless of age or BMI. Males had more major complications (23.6% vs 17.7%, P = 0.03), particularly wound dehiscence or infection, and a 2-day longer hospital stay., Conclusions: This study shows that sarcopenic and myosteatotic obesity phenotypes are highly prevalent, especially in male general surgery patients, regardless of age or BMI. Importantly, sarcopenic and myosteatostic obesity may be more detrimental than visceral obesity; these phenotypes robustly associated with adverse postoperative outcomes. Future work could use these findings for design of phenotype-specific interventions to reduce patient risk and prevent outcomes that are harmful and costly., Competing Interests: Conflict of Interest Alexander Jones declares that he has no conflict of interest. Heidi J. Silver declares that she has no conflict of interest., (Copyright © 2023 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Clinical guidelines disagree on whether the identification of abnormal urine chemistries should occur before starting diet and medication interventions to prevent the recurrence of kidney stone events. We describe the rationale and design of the Urinary supersaturation in a Randomized trial among Individuals with Nephrolithiasis comparing Empiric versus selective therapy (URINE) study, a randomized trial comparing two multi-component interventions to improve urinary supersaturation. Participants are randomized (1:1 ratio) to the empiric or selective arm. The target sample size is 56 participants. Adults ≥ 18 years of age with idiopathic calcium stone disease and two symptomatic stone events within the previous 5 years. Exclusion criteria include systemic conditions predisposing to kidney stones and pharmacologic treatment for stone prevention at baseline. Participants in the empiric arm receive standard diet therapy recommendations, thiazide, and potassium citrate. Participants in the selective arm receive tailored diet and nutrient recommendations and medications based on baseline and 1-month follow-up of 24-h urine testing results. The primary endpoints are urinary supersaturations of calcium oxalate and calcium phosphate at 2 months of follow-up. Secondary endpoints include side effects, diet and medication adherence, and changes in 24-h urine volume, calcium, oxalate, citrate, and pH. Short-term changes in urinary supersaturation may not reflect changes in future risk of stone events. The URINE study will provide foundational data to compare the effectiveness of two prevention strategies for kidney stone disease., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Factors that determine resting energy expenditure (REE) remain under investigation, particularly in persons with a high body mass index (BMI). The accurate estimation of energy expenditure is essential for conducting comprehensive nutrition assessments, planning menus and meals, prescribing weight and chronic disease interventions, and the prevention of malnutrition. This study aimed to: (a) determine the contribution of cardiometabolic biomarkers to the inter-individual variation in REE in persons categorized by BMI; and (b) assess the contribution of these biomarkers in the prediction of REE when persons of varying BMI status were categorized by their glycemic and metabolic syndrome status. Baseline data from 645 adults enrolled in diet intervention trials included REE measured by indirect calorimetry, body composition by dual energy X-ray absorptiometry, anthropometrics, and cardiometabolic biomarkers. Multivariate linear regression modeling was conducted to determine the most parsimonious model that significantly predicted REE by BMI category, metabolic syndrome status, and glycemic status. Modeling with the traditional predictors (age, sex, height, weight) accounted for 58-63% of the inter-individual variance in REE. When including age, sex, height, weight and fat-free mass as covariates, adding TG/HDL to regression modeling accounted for 71-87% of the variance in REE. The finding that TG/HDL is an independent predictor in estimating REE was further confirmed when participants were categorized by metabolic syndrome status and by glycemic status. The clinical utility of calculating the TG/HDL ratio not only aids health care providers in identifying patients with impaired lipid metabolism but can optimize the estimation of REE to better meet therapeutic goals for weight and disease management.

Introduction: This is the first randomized controlled diet intervention trial to investigate both the amount and type of carbohydrate on symptomatic gastroesophageal reflux disease (GERD)., Methods: Ninety-eight veterans with symptomatic GERD were randomly assigned to high total/high simple, high total/low simple, low total/high simple, or low total/low simple carbohydrate diet for 9 weeks. The primary outcomes were esophageal acid exposure time (AET) and total number of reflux episodes derived from 24-hour ambulatory pH monitoring. Secondary outcomes were esophageal reflux symptoms rated using the Gastroesophageal Reflux Disease Questionnaire (GERDQ) and GERD Symptom Assessment Scale (GSAS)., Results: Half of the subjects were White and half African American (mean age, 60.0 ± 12.5 years; mean body mass index, 32.7 ± 5.4 kg/m 2 ). There was a significant main effect of diet treatment on AET ( P = 0.001) and on the total number of reflux episodes ( P = 0.003). The change in AET in the high total/low simple group (-4.3% ± 3.8%) differed significantly from the high total/high simple control group (+3.1% ± 3.7%), (P = 0.04). The reduction in simple sugar intake averaged 62 g less per day. Subjects' ratings of symptoms improved in all carbohydrate modification groups, including significant reductions in heartburn frequency, heartburn severity, acid taste in the mouth, lump/pain in the throat or chest, and sleep disturbance., Discussion: A modification of dietary carbohydrate intake that targeted a substantial reduction in the intakes of simple sugars improved pH monitoring outcomes and symptoms of GERD that profoundly affect daily life. These findings provide a feasible and clinically applicable contribution to the limited objective data existing for efficacious dietary recommendations in the routine treatment and management of GERD., (Copyright © 2022 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a "work of the United States Government" for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

Many diseases linked with ethnic health disparities associate with changes in microbial communities in the United States, but the causes and persistence of ethnicity-associated microbiome variation are not understood. For instance, microbiome studies that strictly control for diet across ethnically diverse populations are lacking. Here, we performed multiomic profiling over a 9-day period that included a 4-day controlled vegetarian diet intervention in a defined geographic location across 36 healthy Black and White females of similar age, weight, habitual diets, and health status. We demonstrate that individuality and ethnicity account for roughly 70% to 88% and 2% to 10% of taxonomic variation, respectively, eclipsing the effects a short-term diet intervention in shaping gut and oral microbiomes and gut viromes. Persistent variation between ethnicities occurs for microbial and viral taxa and various metagenomic functions, including several gut KEGG orthologs, oral carbohydrate active enzyme categories, cluster of orthologous groups of proteins, and antibiotic-resistant gene categories. In contrast to the gut and oral microbiome data, the urine and plasma metabolites tend to decouple from ethnicity and more strongly associate with diet. These longitudinal, multiomic profiles paired with a dietary intervention illuminate previously unrecognized associations of ethnicity with metagenomic and viromic features across body sites and cohorts within a single geographic location, highlighting the importance of accounting for human microbiome variation in research, health determinants, and eventual therapies. Trial Registration: ClinicalTrials.gov ClinicalTrials.gov Identifier: NCT03314194., Competing Interests: The authors have declared that no competing interests exist.

Background: Rising prevalence of gastroesophageal reflux disease (GERD) in US Veterans is concurrent with increasing excess body weight., Objective: The objective of this cross-sectional study is to examine relationships between dietary macronutrients, gastrointestinal hormones, and GERD status., Methods: Ninety-eight veterans with overweight/obesity and empiric proton pump inhibitor (PPI) treatment were enrolled from the Tennessee Valley Healthcare System. Subjects had esophageal manometry and 24-h pH monitoring. Subjective symptoms were assessed with Gastroesophageal Reflux Disease Questionnaire (GERDQ) and Symptom Assessment Scale (GSAS). The primary outcomes, total acid exposure time (AET) and number of reflux episodes, enabled categorizing subjects as either pathologic GERD or inconclusive GERD. Data analysis included independent T -tests, Spearman Rho correlations, and multivariable linear regression modeling., Results: Higher intake of sugar-sweetened beverages (sugar-sweetened tea, soda, and fruit juice) associated with higher AET. Higher saturated-to-unsaturated fat intake is associated with higher AET and number of reflux episodes. Overall, sugar-sweetened beverage intake, saturated-to-unsaturated fat ratio, tomato-based food items, glucagon-like polypeptide 1 (GLP-1) level, time of first meal, and education status accounted for a significant amount of the variability in AET. Pathologic GERD subjects reported more heartburn ( p  = 0.006), regurgitation ( p  = 0.01), acid taste (0.001), and nausea severity ( p  = 0.04). GERDQ score associated with AET ( r  = 0.31, p  = 0.005), but GSAS did not ( r  = 0.12, p  = 0.28)., Conclusion: Of the many foods and nutrients tested, the type (not amount) of carbohydrate (simple sugars) and the type (not amount) of fat (saturated vs unsaturated fat) consumed associated with objective and/or subjective GERD testing. These novel findings contribute to the evidence base guiding specific dietary recommendations in the clinical management of GERD., Competing Interests: Conflict of interest statement: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2022.)

Background/objectives: Hypothalamic obesity (HO) frequently occurs following suprasellar tumors from a combination of decreased energy expenditure and increased energy intake. Glucagon-like peptide-1 receptor agonist (GLP1RA) therapy is associated with increased satiety and energy expenditure. We hypothesized GLP1RA therapy in patients with HO would cause both lower energy intake and increased energy expenditure., Subjects/methods: Forty-two patients aged 10-26 years (median 16 years) with HO with suprasellar tumors were randomized to GLP1RA (exenatide extended release once-weekly, ExQW, n = 23) or placebo (n = 19). Thirty seven (81%) patients completed the 36-week double-blind placebo-controlled trial. Total energy expenditure (TEE) was measured with doubly labeled water, physical activity was assessed with actigraphy, and intake was estimated with ad libitum buffet meal. Results are presented as adjusted mean between-group difference., Results: As compared with treatment with placebo, treatment with ExQW was associated with decreased energy intake during a buffet meal (-1800 kJ (-430 kcal), 95% CI -3 184 to -418 kJ, p = 0.02). There were no significant differences in physical activity between groups. ExQW (vs. placebo) treatment was associated with a decrease in TEE (-695 kJ/day (-166 kcal/day), 95% CI -1 130 to -264 kJ/day, p < 0.01, adjusted for baseline TEE). The treatment effect was still significant after further adjustment for change in body composition (-372 kJ/day (-89 kcal/day), 95% CI -699 to -42 kJ/day, p = 0.04) or change in leptin (-695 kJ/day (-166 kcal/day), 95% CI -1 130 to -264 kJ/day, p < 0.01). This decrease in TEE occurred despite an increase in lean mass and fat mass (1.7 vs. 1.3 kg lean mass, p = 0.88 and 1.5 vs. 4.6 kg fat mass, p = 0.04, ExQW vs. placebo)., Conclusions: Treatment with a GLP1RA was associated with a decrease in food intake but also a decrease in TEE that was disproportionate to change in body composition., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: Body mass index (BMI) is the most commonly used predictor of weight-related comorbidities and outcomes. However, the presumed relationship between height and weight intrinsic to BMI may introduce bias with respect to prediction of clinical outcomes. A series of analyses comparing the performance of models representing weight and height as separate interacting variables to models using BMI were performed using Vanderbilt University Medical Center's deidentified electronic health records and landmark methodology., Methods: Use of BMI or height-weight interaction in prediction models for established weight-related cardiometabolic traits and metabolic syndrome was evaluated. Specifically, prediction models for hypertension, diabetes mellitus, low high-density lipoprotein, and elevated triglycerides, atrial fibrillation, coronary artery disease, heart failure, and peripheral artery disease were developed. Model performance was evaluated using likelihood ratio, R 2 , and Somers' Dxy rank correlation. Differences in model predictions were visualized using heat maps., Results: Compared to BMI, the maximally flexible height-weight interaction model demonstrated improved prediction, higher likelihood ratio, R 2 , and Somers' Dxy rank correlation, for event-free probability for all outcomes. The degree of improvement to the prediction model differed based on the outcome and across the height and weight range., Conclusions: Because alternative measures of body composition such as waist-to-hip ratio are not routinely collected in the clinic clinical risk models quantifying risk based on height and weight measurements alone are essential to improve practice. Compared to BMI, modeling height and weight as independent, interacting variables results in less bias and improved predictive accuracy for all tested traits. Considering an individual's height and weight opposed to BMI is a better method for quantifying individual disease risk., Competing Interests: J. Beckman declares potential conflicts with Amgen, Bayer, Glaxo Smith Kline, Janssen, Novartis, and Sanofi in the past 12months. All other authors declare no conflicts of interest., (© 2021 The Authors. Obesity Science & Practice published by World Obesity and The Obesity Society and John Wiley & Sons Ltd.)

Background and Aims: The type of fat consumed in animal-based western diets, typically rich in the saturated fat palmitate, has been implicated in cardiometabolic disease risk. In contrast, the most abundant mono- and polyunsaturated fats, more typical in a vegetarian or plant-based diet, potentiate less deleterious effects. This study determined differences in plasma and urine metabolites when switching from omnivorous to vegetarian diet, including metabolites involved in fatty acid utilization., Methods and Results: A prospective cohort of 38 European (EA) and African American (AA) omnivorous females were matched by age (25.7 ± 5.3y) and BMI (22.4 ± 1.9 kg/m 2 ). Pre-intervention samples were collected while subjects consumed habitual animal-based diet. Changes in metabolites were assessed by ultra-high-performance liquid chromatography-tandem mass spectroscopy (Metabolon, Inc.) upon completing four days of novel vegetarian diet provided by the Vanderbilt Metabolic Kitchen. Changes in several diet-derived metabolites were observed, including increases in compounds derived from soy food metabolism along with decreases in metabolites of xanthine and histidine. Significant changes occurred in metabolites of saturated, monounsaturated and polyunsaturated fatty acids along with significant differences between EA and AA women in changes in plasma concentrations of acylcarnitines, which reflect the completeness of fatty acid oxidation (versus storage)., Conclusion: These data suggest improvements in fatty acid metabolism (oxidation vs storage), a key factor in energy homeostasis, may be promoted rapidly by adoption of a vegetarian (plant-based) diet. Mechanistic differences in response to diet interventions must be understood to effectively provide protection against the widespread development of obesity and cardiometabolic disease in population subgroups, such as AA women., Competing Interests: Declaration of competing interest The authors have no conflicts with the present study to report., (Copyright © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Purpose: Obesity (body mass index 30 kg/m 2 or greater) is associated with better overall survival in metastatic prostate cancer. Conversely, low muscle mass (sarcopenia) and low muscle radiodensity (myosteatosis) are associated with worse overall survival in many cancers. This study seeks to evaluate the relationship of sarcopenia, myosteatosis and obesity with overall survival in men with metastatic or castrate-resistant prostate cancer., Materials and Methods: Retrospective analysis of men with metastatic or castrate-resistant prostate cancer and computerized tomography of abdomen/pelvis presenting to the Vanderbilt Comprehensive Prostate Cancer Clinic from 2012 to 2017 was performed. Demographic, pathological and survival data were described, with sarcopenia and myosteatosis determined from abdominal skeletal muscle area and skeletal muscle radiodensity, respectively. Kaplan-Meier curves and log-rank tests estimated the effect of body composition on survival. Multivariable Cox proportional hazard models were performed adjusting for age, Charlson comorbidity index, race and clinical stage. ANOVA was used to compare obese and nonobese men with and without sarcopenia or myosteatosis., Results: Of 182 men accrued, 37.4% were obese, 53.3% sarcopenic and 59.3% myosteatotic. Over a median followup of 33.9 months, body mass index was associated with reduced mortality (HR 0.93, p=0.02), as was visceral adiposity (HR 0.99, p=0.003). Men with high body mass index without sarcopenia/myosteatosis lived significantly longer than men with high body mass index with sarcopenia/myosteatosis or normal body mass index men (F[3,91]=4.03, p=0.01)., Conclusions: Both high body mass index and visceral adiposity in metastatic or castrate-resistant prostate cancer are associated with reduced mortality, independent of sarcopenia and myosteatosis. Therefore, routine clinical workup should include calculation of body mass index and measurement of waist circumference. Morphometric analysis of computerized tomography imaging can identify patients at risk for poor prognosis.

Background: Low-income racially and ethnically diverse children are at higher risk for obesity compared with their counterparts; yet, few studies have assessed their diet quality., Objective: The aim of the study was to evaluate the diet quality of a racially and ethnically diverse cohort of 2-year-olds using the Healthy Eating Index (HEI)-2010., Methods: We used 24-hour dietary recall data from caregivers of toddlers (24-34 months) at 4 pediatric resident clinics that participated in the Greenlight Study to calculate compliance with the Dietary Guidelines for Americans (DGA) using total HEI score (range 0-100) and 12 component scores., Results: Participants (n = 231) were mostly Hispanic (57%) or non-Hispanic black (27%) and from low-income families. Mean HEI-2010 score was 62.8 (standard deviation [SD] 10.5). Though not significant, Hispanics had the highest HEI score. Toddlers of caregivers without obesity, older than 35 years and born outside the United States had higher HEI scores. Most had high HEI component scores for dairy, fruit, and protein foods, but few achieved maximum scores, particularly for whole grains (13%), vegetables (10%), and fatty acid ratio (7%)., Conclusions: Despite scores reflective of DGA recommendations for fruit, dairy and protein foods, toddlers in this diverse sample had low quality diets as measured by the HEI, driven largely by low component scores for whole grains, vegetables, and ratio of unsaturated to saturated fatty acids.

Background: Calorie-dense diet is a main driver of the global epidemics of obesity and type 2 diabetes (T2DM). While various dietary strategies and patterns are efficacious in reducing risk and improving glycemic control, dietary intake and diet quality have been inadequately studied among individuals who remain living in their native environments. There is also little published on dietary patterns of diverse ethnic, cultural, or regional populations., Objective: To explore dietary intakes, patterns and overall diet quality in adults with obesity and T2DM from diverse countries. We hypothesized that individuals sharing a common clinical phenotype (age, BMI, years since T2DM diagnosis and inadequate glycemic control) would demonstrate comparable high calorie "western" dietary patterns and low diet quality despite differences in geographic regions and cultures., Design: Diet data were acquired from 611 adults in Argentina, Germany, Poland, Serbia, Slovakia, Slovenia, Spain, Turkey and the USA via three 24-h diet recalls. Contribution of 168 foods to 14 primary food groups was confirmed by Spearman's rank-order correlations and Principle Component Factor Analysis identified dietary patterns. Diet quality was assessed using the Healthy Eating Index 2015., Results: Eleven dietary patterns were extracted; the most common were a "Mediterranean-like" pattern shared by six countries and a "Calorie Dense" pattern shared by five countries. Also common were "Lacto-Vegetarian, "Pesco-Vegetarian," and "Vegan" patterns. Only 2.1% of subjects had good diet quality (HEI-2015 score >80)., Conclusions: The diet pattern data suggest that influences of more traditional region-specific diets remain. However, overall diet quality was poor and may contribute to inadequate glycemic control, possibly due to excess intake of high calorie/nutrient poor foods, which may be associated with global transitions occurring in the available food supply.

Background: Aerobic exercise training is known to have beneficial effects on whole-body glucose metabolism in people with type 2 diabetes (T2D). The responses of the liver to such training are less well understood. The purpose of this study was to determine the effect of aerobic exercise training on splanchnic glucose uptake (SGU) and insulin-mediated suppression of endogenous glucose production (EGP) in obese subjects with T2D., Methods: Participants included 11 obese humans with T2D, who underwent 15 ± 2 weeks of aerobic exercise training (AEX; n = 6) or remained sedentary for 15 ± 1 weeks (SED; n = 5). After an initial screening visit, each subject underwent an oral glucose load clamp and an isoglycemic/two-step (20 and 40 mU/m 2 /min) hyperinsulinemic clamp (ISO-clamp) to assess SGU and insulin-mediated suppression of EGP, respectively. After the intervention period, both tests were repeated., Results: In AEX, the ability of insulin to suppress EGP was improved during both the low (69 ± 9 and 80 ± 6% suppression; pre-post, respectively; p < 0.05) and high (67 ± 6 and 82 ± 4% suppression, respectively; p < 0.05) insulin infusion periods. Despite markedly improved muscle insulin sensitivity, SGU was reduced in AEX after training (22.9 ± 3.3 and 9.1 ± 6.0 g pre-post in AEX, respectively; p < 0.05)., Conclusions: In obese T2D subjects, exercise training improves whole-body glucose metabolism, in part, by improving insulin-mediated suppression of EGP and enhancing muscle glucose uptake, which occur despite reduced SGU during an oral glucose challenge.

Malnutrition is a leading cause of morbidity and mortality, especially among older adults. However, diagnosis and treatment of malnutrition in the hospital setting are often overlooked. In recent years, quality improvement (QI) initiatives to increase the assessment and treatment of malnutrition in hospital settings have been implemented and shown to improve both patient health and economic outcomes. The Malnutrition Quality Improvement Initiative (MQii) Toolkit was designed in an effort to support hospitals seeking to implement malnutrition QI initiatives. The Toolkit has been implemented, studied, and updated for optimization of content, adaptability, and usability over several cycles of improvement from 2016-2017 at more than 50 hospital centers in the United States. The result is an open access, customizable, and user-friendly MQii Toolkit that can facilitate the implementation of malnutrition QI initiatives in individual facilities. This article introduces the MQii Toolkit, describes the process by which it was designed and improved, and orients clinical care teams to its use. FUNDING/SUPPORT: Publication of this supplement was supported by Abbott. The Academy of Nutrition and Dietetics does not receive funding for the MQii. Avalere Health's work to support the MQii was funded by Abbott., (Copyright © 2019 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Purpose: We designed a prospective randomized, controlled pilot trial to investigate the effects of an enriched oral nutrition supplement on body composition and clinical outcomes following radical cystectomy., Materials and Methods: A total of 61 patients were randomized to an oral nutrition supplement or a multivitamin multimineral supplement twice daily during an 8-week perioperative period. Body composition was determined by analyzing abdominal computerized tomography images at the L3 vertebra. Sarcopenia was defined as a skeletal muscle index of less than 55 cm/m in males and less than 39 cm/m in females. The primary outcome was the difference in 30-day hospital free days. Secondary outcomes included hospital length of stay, complications, readmissions and mortality., Results: The oral nutrition supplement group lost less weight (-5 vs -6.5 kg, p = 0.04) compared to the multivitamin multimineral supplement group. The proportion of patients with sarcopenia did not change in the oral nutrition supplement group but increased 20% in the multivitamin multimineral supplement group (p = 0.01). Mean length of stay and 30-day hospital free days were similar in the groups. The oral nutrition supplement group had a lower rate of overall and major (Clavien grade 3 or greater) complications (48% vs 67% and 19% vs 25%, respectively) and a lower readmission rate (7% vs 17%) but the differences did not reach statistical significance., Conclusions: Patients who undergo radical cystectomy after consuming an oral nutrition supplement perioperatively have a reduced prevalence of sarcopenia and may also experience fewer and less severe complications and readmissions. A larger blinded, randomized, controlled trial is necessary to determine whether oral nutrition supplement interventions can improve outcomes following radical cystectomy.

Background: We previously reported that consuming a balanced high fat diet (BHFD) wherein total saturated fat was reduced and total unsaturated fat increased by proportionately balancing the type of fat (1/3 saturated, 1/3 monounsaturated, 1/3 polyunsaturated) led to significant improvements in inflammatory burden, blood pressure, and vascular function in obese premenopausal European American (EA) and African American (AA) women., Objective: Here we compared changes in adipose tissue, lipoproteins, insulin resistance, and cardiovascular risk between EA and AA women., Methods: Dietary intakes, plasma fatty acids, lipids, apolipoproteins, lipoproteins, HOMA-IR and ASCVD risk was measured in 144 women who consumed BHFD for 16 weeks. Generalized linear modeling was performed while controlling for change in body weight., Results: EA women had greater reductions in visceral adipose tissue. Only EA women had significant reductions in fasting insulin levels (↓24.8%) and HOMA-IR (↓29%) scores. In EA women, the most significant improvements occurred in VLDL particle size (↑), apolipoprotein B levels (↑), serum TG (↓), number of plasma LDL particles (↓), and serum LDL-cholesterol (↓). In AA women, significant improvements occurred in HDL particle size (↑), number of large HDL particles (↑), and apolipoprotein AI levels (↑). Consequently, both groups had improved ASCVD risk scores (↓5.5%)., Conclusions: Consuming the balanced high fat diet led to significant reduction in cardiovascular risk factors in both groups. However, the pattern of response to BHFD differed with EA women responding more in components of the apolipoprotein B pathway versus AA women responding more in components of the apolipoprotein AI pathway., (Published by Elsevier Inc.)

Background: Sucrose-isomaltase deficiency (SID) remains underdiagnosed. Absent or reduced enzyme activity promotes diarrhea, abdominal bloating, and flatulence from undigested and malabsorbed disaccharides. Frequency and severity of gastrointestinal symptoms may be associated with the type of carbohydrates consumed., Objective: To characterize the dietary intakes of patients treated with sacrosidase (Sucraid; QOL Medical) for SID and determine relationships between type of carbohydrates, sacrosidase dose, and gastrointestinal symptoms., Design: A prospective 30-day observational study., Participants/setting: Forty-nine patients treated with sacrosidase for ≥3 months were recruited from the enzyme manufacturer's nationwide clinical database between November 2014 and August 2015., Main Outcome Measures: Dietary energy and nutrient intakes reported during 24-hour diet recall interviews, frequency and severity of gastrointestinal (GI) symptoms, and sacrosidase dose., Statistical Analyses Performed: Relationships between nutrient intakes, sacrosidase dose, and GI symptoms were evaluated using Spearman ρ correlation coefficients., Results: Sacrosidase dose averaged 5.2±3.1 mL/day. Participants reported 1.3±0.9 bowel movements daily. Having less frequent GI symptoms was associated with higher sacrosidase intake. Energy intakes averaged 1,562.5±411.5 kcal/day in children, 1,964.7±823.6 kcal/day in adolescents, and 1,952.6±546.5 kcal/day in adults. Macronutrient composition averaged 44% carbohydrate, 39% fat, and 17% protein. Average carbohydrate composition was 35% starch, 8% fiber, and 59% sugars. Sucrose and fructose intakes were not associated with GI symptoms. Lactose intake was associated with diarrhea. Maltose intake was associated with nausea, distension, and reflux., Conclusions: Intakes were lower in carbohydrates and higher in fat compared with the Acceptable Macronutrient Distribution Ranges. Sucrose and fructose intakes were not associated with GI symptoms. Higher maltose and lactose intakes were associated with GI symptom frequency and severity. These findings provide evidence to guide nutrition counseling for patients treated for SID., (Copyright © 2018 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Background: Malnutrition is present in 30% to 50% of hospitalized patients aged 60 years or older. As few as 3.2% of patients identified as high risk have a malnutrition diagnosis documented by medical providers. The Malnutrition Quality Improvement Initiative (MQii) aims to reduce the burden of hospital malnutrition by improving the process and delivery of care., Objective: To evaluate implementing the MQii toolkit of best practice resources for screening, diagnosis, documentation, and timeliness of malnutrition care., Design: This 6-month prospective pilot included a 3-month intervention with training and education modules tailored to type of practitioner and integrated into existing teaching and clinical workflow., Participants/setting: Forty-five health care professionals from geriatric, general medicine, and general surgery units at Vanderbilt University Hospital during January to June 2016., Main Outcome Measures: Malnutrition knowledge by 30-item questionnaire; electronic medical record (EMR) documentation; and timeliness of malnutrition screening, diagnosis, intervention, and discharge planning., Statistical Analyses: Analysis of variance was used to test change over time., Results: Malnutrition knowledge score increased 14%, from 39% to 53% (P=0.009). All patients whose nutrition screen indicated they were malnourished/high risk had registered dietitian nutritionist diagnosis of malnutrition documented in the EMR. The proportion who had medical provider (physician, nurse practitioner, or physician assistant) malnutrition diagnosis documented in the EMR increased 11.6%, from 26.7% to 38.3% (P=0.08). About 95% of malnourished/high risk patients had a documented intervention addressing malnutrition. Inclusion of malnutrition care in the discharge plan increased 4.8%, from 70.0% to 74.8% (P=0.13)., Conclusions: This pilot study demonstrated feasibility of implementing the MQii resources to improve malnutrition knowledge and professionals' skills relevant to screening, diagnosis, intervention, and timeliness of malnutrition care. By optimizing the process and delivery of malnutrition care, it is expected that the quality of clinical care provided to older adults with malnutrition or at high malnutrition risk will improve., (Copyright © 2018 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Central insulin resistance (IR) influences striatal dopamine (DA) tone, an important determinant of behavioral self-regulation. We hypothesized that an association exists between the degree of peripheral IR and impulse control, mediated by the impact of IR on brain circuits controlling the speed of executing "go" and/or "stop" responses. We measured brain activation and associated performance on a stop signal task (SST) in obese adults with type 2 diabetes (age, 48.1 ± 6.9 yrs (mean ± SD); BMI, 36.5 ± 4.0 kg/m2; HOMA-IR, 7.2 ± 4.1; 12 male, 18 female). Increasing IR, but not BMI, was a predictor of shorter critical stop signal delay (cSSD), a measure of the time window during which a go response can be successfully countermanded (R2 = 0.12). This decline was explained by an IR-associated increase in go speed (R2 = 0.13) with little impact of IR or BMI on stop speed. Greater striatal fMRI activation contrast in stop error (SE) compared with stop success (SS) trials (CONSE>SS) was a significant predictor of faster go speeds (R2 = 0.33, p = 0.002), and was itself predicted by greater IR (CONSE>SS vs HOMA-IR: R2 = 0.10, p = 0.04). Furthermore, this impact of IR on striatal activation was a significant mediator of the faster go speeds and greater impulsivity observed with greater IR. These findings suggest a neural mechanism by which IR may increase impulsivity and degrade behavioral self-regulation.