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Due to the rising prevalence of obesity and its impact on healthcare, patient-specific context is needed to optimize weight management with an emphasis on reducing health care-associated weight stigma. Our survey aimed to explore institution-specific patient experiences of weight stigma and preferences for patient-centered language use regarding weight management care. This cross-sectional analysis adopted a concurrent mixed methods design with a sample of individuals who opted in to complete patient experience surveys after receiving care at a large academic medical center in the United States (U.S.). Categorical and continuous variables were assessed using Chi-squared and analysis of variance. We used classical content analysis to qualitatively analyze free-text data for thematic coding. After a 1-week survey fielding period, 3,219 of 16,758 patients completed the survey, yielding a response rate of (19.2%) with 2,816 having available electronic health record body mass index (BMI) data. Patients were comfortable discussing weight with their primary care providers but showed variation in the preferred approach and terms. Female patients with higher BMIs reported higher rates of delayed and canceled care due to prior weight stigma (25.6% and 12.2% for patients with class 3 obesity), and preferred a slower, gentler, and less direct approach with term preferences for \"healthy eating plan\" and against \"obesity.\" Qualitative analysis yielded 27 themes grouped into three domains: Emotional Hinderances, Perceptual Hinderances, and Perceived Helpfulness. Findings from our large single institution cohort expand on the existing weight stigma literature by identifying patient language preferences and healthcare experiences according to patient weight class and sex. Given the potential impact of understanding context-specific patient language use preferences to reduce weight stigma, we recommend other healthcare systems use a similar process to address weight stigma as part of a coordinated health system improvement initiative to enhance patient-centered weight management care.

ObjectiveDiabetes and cardiovascular diseases are growing burdens in rural communities worldwide. We have observed a high prevalence of diabetes among rural farming communities in India and sought to evaluate the association of non-traditional risk factors, such as metals, with diabetes and other cardiometabolic risk factors in this community.MethodsAnthropometric measurements, chemistries and carotid intima-media thickness were determined in 865 participants of the Kovai Medical Center and Hospital-Nallampatti Non-Communicable Disease Study-I (KMCH-NNCD-I, 2015), a cross-sectional study conducted in a farming village in South India. Urinary metal levels were determined by inductively couped plasma-mass spectrometry analysis and corrected to urinary creatinine level. Statistical analyses were performed to study the association between urinary metal levels and clinical parameters.Results82.5% of the study population were involved in farming and high levels of toxic metals were detected in the synthetic fertilisers used in the study village. The prevalence of pre-diabetes, diabetes and atherosclerosis was 43.4%, 16.2% and 10.3%, respectively. On logistic regression analysis, no association of traditional risk factors such as body mass index, blood pressure and total cholesterol with disease conditions was observed, but urinary levels of metals such as arsenic, chromium, aluminium and zinc showed an association with diabetes, while arsenic and zinc showed an association with pre-diabetes and atherosclerosis.ConclusionsOur data suggest a probable role of metals in the aetiology of diabetes and cardiovascular diseases in rural communities. Identifying and eliminating the causes of increased levels of these environmental chemicals could have a beneficial impact on the burden of non-communicable diseases in rural population.

A Preprandial Rise in Plasma Ghrelin Levels Suggests a Role in Meal Initiation in Humans David E. Cummings 1 , Jonathan Q. Purnell 2 , R. Scott Frayo 1 , Karin Schmidova 1 , Brent E. Wisse 1 and David S. Weigle 1 1 University of Washington, VA Puget Sound Health Care System and Harborview Medical Center, Seattle, Washington 2 Oregon Health Sciences University, Portland, Oregon Abstract The recently discovered orexigenic peptide ghrelin is produced primarily by the stomach and circulates in blood at levels that increase during prolonged fasting in rats. When administered to rodents at supraphysiological doses, ghrelin activates hypothalamic neuropeptide Y/agouti gene–related protein neurons and increases food intake and body weight. These findings suggest that ghrelin may participate in meal initiation. As a first step to investigate this hypothesis, we sought to determine whether circulating ghrelin levels are elevated before the consumption of individual meals in humans. Ghrelin, insulin, and leptin were measured by radioimmunoassay in plasma samples drawn 38 times throughout a 24-h period in 10 healthy subjects provided meals on a fixed schedule. Plasma ghrelin levels increased nearly twofold immediately before each meal and fell to trough levels within 1 h after eating, a pattern reciprocal to that of insulin. Intermeal ghrelin levels displayed a diurnal rhythm that was exactly in phase with that of leptin, with both hormones rising throughout the day to a zenith at 0100, then falling overnight to a nadir at 0900. Ghrelin levels sampled during the troughs before and after breakfast correlated strongly with 24-h integrated area under the curve values ( r = 0.873 and 0.954, respectively), suggesting that these convenient, single measurements might serve as surrogates for 24-h profiles to estimate overall ghrelin levels. Circulating ghrelin also correlated positively with age ( r = 0.701). The clear preprandial rise and postprandial fall in plasma ghrelin levels support the hypothesis that ghrelin plays a physiological role in meal initiation in humans. Footnotes Address correspondence and reprint requests to David E. Cummings, Assistant Professor of Medicine, University of Washington, VA Puget Sound Health Care System, Seattle Division, 1660 S. Columbian Way, S-111-Endo, Seattle, WA 98108. E-mail: davidec{at}u.washington.edu . Received for publication 25 April 2001 and accepted in revised form 30 May 2001. Posted on the World Wide Web at www.diabetes.org/diabetes on 29 June 2001. AGRP, agouti gene–related protein; AUC, area under the curve; CV, coefficient of variation; GH, GH; GHS, GH secretagogue; NPY, neuropeptide Y; RIA, radioimmunoassay.

ObjectiveIncreased infant birth weight and adiposity are associated with an altered risk of adult chronic diseases. The objective was to investigate the association between maternal dietary fat intake during pregnancy and newborn adiposity.Study designThe study included 79 singleton pregnancies. Associations between maternal dietary fat intake during each trimester and infant adiposity at birth were assessed.ResultAverage total grams of maternal total dietary fat and unsaturated fat intake during pregnancy correlated with infant percent body fat after adjusting for potential confounding variables (r = 0.23, p = 0.045; r = 0.24, p = 0.037). Maternal average daily intake of total fat, saturated fat, and unsaturated fat during the second trimester of pregnancy were each associated with infant percent body fat (r = 0.25, p = 0.029; r = 0.23, p = 0.046; r = 0.25, p = 0.031; respectively).ConclusionsThe second trimester of pregnancy is a key time period for fetal adipose tissue metabolic programming and therefore a target for nutritional intervention.

Background An international panel of obesity medicine experts from multiple professional organizations examined patterns of obesity care and current obesity treatment guidelines to identify areas requiring updating in response to emerging science and clinical evidence. Aims The panel focused on multiple medical health and societal issues influencing effective treatment of obesity and identified several unmet needs in the definition, assessment, and care of obesity. Methods The panel was held in Leesburg, Virginia in September 2019. Results The panelists recommended addressing these unmet needs in obesity medicine through research, education, evaluation of delivery and payment of care, and updating clinical practice guidelines (CPG) to better reflect obesity’s pathophysiological basis and heterogeneity, as well as the disease’s health, sociocultural, and economic complications; effects on quality of life; need for standards for quantitative comparison of treatment benefits, risks, and costs; and the need to more effectively integrate obesity treatment guidelines into routine clinical practice and to facilitate more direct clinician participation to improve public understanding of obesity as a disease with a pathophysiological basis. The panel also recommended that professional organizations working to improve the care of people with obesity collaborate via a working group to develop an updated, patient‐focused, comprehensive CPG establishing standards of care, addressing identified needs, and providing for routine, periodic review and updating. Conclusions Unmet needs in the definition, assessment and treatment of obesity were identified and a blueprint to address these needs developed via a clinical practice guideline that can be utilized worldwide to respond to the increasing prevalence of obesity.

There is marked heterogeneity in the response to weight loss interventions with regards to weight loss amount and metabolic improvement. We sought to identify biomarkers predictive of type 2 diabetes remission and amount of weight loss in individuals with severe obesity enrolled in the Longitudinal Assessment of Bariatric Surgery (LABS) and the Look AHEAD (Action for Health in Diabetes) studies. Targeted mass spectrometry-based profiling of 135 metabolites was performed in pre-intervention blood samples using a nested design for diabetes remission over five years (n = 93 LABS, n = 80 Look AHEAD; n = 87 remitters), and for extremes of weight loss at five years (n = 151 LABS; n = 75 with high weight loss). Principal components analysis (PCA) was used for dimensionality reduction, with PCA-derived metabolite factors tested for association with both diabetes remission and weight loss. Metabolic markers were tested for incremental improvement to clinical models, including the DiaRem score. Two metabolite factors were associated with diabetes remission: one primarily composed of branched chain amino acids (BCAA) and tyrosine (odds ratio (95% confidence interval) [OR (95% CI)] = 1.4 [1.0–1.9], p = 0.045), and one with betaine and choline (OR [95% CI] = 0.7 [0.5–0.9], p = 0.02).These results were not significant after adjustment for multiple tests. Inclusion of these two factors in clinical models yielded modest improvements in model fit and performance: in a constructed clinical model, the C-statistic improved from 0.87 to 0.90 (p = 0.02), while the net reclassification index showed improvement in prediction compared to the DiaRem score (NRI = 0.26, p = 0.0013). No metabolite factors associated with weight loss at five years. Baseline levels of metabolites in the BCAA and trimethylamine-N-oxide (TMAO)-microbiome-related pathways are independently and incrementally associated with sustained diabetes remission after weight loss interventions in individuals with severe obesity. These metabolites could serve as clinically useful biomarkers to identify individuals who will benefit the most from weight loss interventions.

Obesity and type 2 diabetes are prevalent chronic diseases effectively managed by semaglutide. Here we studied the effects of semaglutide on the circulating proteome using baseline and end-of-treatment serum samples from two phase 3 trials in participants with overweight or obesity, with or without diabetes: STEP 1 ( n  = 1,311) and STEP 2 ( n  = 645). We identified evidence supporting broad effects of semaglutide, implicating processes related to body weight regulation, glycemic control, lipid metabolism and inflammatory pathways. Several proteins were regulated with semaglutide, after accounting for changes in body weight and HbA 1c at end of trial, suggesting effects of semaglutide on the proteome beyond weight loss and glucose lowering. A comparison of semaglutide with real-world proteomic profiles revealed potential benefits on disease-specific proteomic signatures including the downregulation of specific proteins associated with cardiovascular disease risk, supporting its reported effects of lowering cardiovascular disease risk and potential drug repurposing opportunities. This study showcases the potential of proteomics data gathered from randomized trials for providing insights into disease mechanisms and drug repurposing opportunities. These data also highlight the unmet need for, and importance of, examining proteomic changes in response to weight loss pharmacotherapy in future trials. Using serum samples collected from participants of the STEP 1 and STEP 2 trials, the authors have uncovered changes to the proteome upon semaglutide treatment, which can shed light on the mechanism of action of the drug driving its benefits in obesity-related conditions.

Objective In July 2023 a diverse group of international experts from academia, healthcare and medical technology/pharmacological companies gathered to discuss the current global landscape in the management of obesity, identify the clinical challenges healthcare systems are facing, and the gaps in scientific knowledge. Approach We proposed ways that the academia‐industry‐healthcare‐interface can be strengthened to offer solutions to these challenges and fill the gaps in knowledge. Conclusion We identified these five priorities for action: (1) Enhancing the academia‐healthcare‐industry collaboration in a way that prioritizes the patient with obesity and healthcare economic value. (2) Identifying reliable biomarkers and predictors of obesity treatment response to determine as early as possible whether a specific therapy is likely to work. (3) Defining specific and individualized treatment targets that take account of heterogeneity of obesity‐related complications risk, the presence of multimorbidity, and patient preference. (4) Addressing bias and discrimination against people with obesity amongst clinicians, health policy makers and the wider public. (5) Combining randomized controlled trial and cohort study data to apply next generation “machine learning” and “artificial intelligence” methods to large datasets that accelerates identification of factors associated with response heterogeneity and successful treatment response prediction.

Abstract Context Few studies have examined the clinical characteristics that predict durable, long-term diabetes remission after bariatric surgery. Objective To compare diabetes prevalence and remission rates during 7-year follow-up after Roux-en-Y gastric bypass (RYGB) and laparoscopic gastric banding (LAGB). Design An observational cohort of adults with severe obesity recruited between 2006 and 2009 who completed annual research assessments for up to 7 years after RYGB or LAGB. Setting Ten US hospitals. Participants A total sample of 2256 participants, 827 with known diabetes status at both baseline and at least 1 follow-up visit. Interventions Roux-en-Y gastric bypass or LAGB. Main Outcome Measures Diabetes rates and associations of patient characteristics with remission status. Results Diabetes remission occurred in 57% (46% complete, 11% partial) after RYGB and 22.5% (16.9% complete, 5.6% partial) after LAGB. Following both procedures, remission was greater in younger participants and those with shorter diabetes duration, higher C-peptide levels, higher homeostatic model assessment of β-cell function (HOMA %B), and lower insulin usage at baseline, and with greater postsurgical weight loss. After LAGB, reduced HOMA insulin resistance (IR) was associated with a greater likelihood of diabetes remission, whereas increased HOMA-%B predicted remission after RYGB. Controlling for weight lost, diabetes remission remained nearly 4-fold higher compared with LAGB. Conclusions Durable, long-term diabetes remission following bariatric surgery is more likely when performed soon after diagnosis when diabetes medication burden is low and beta-cell function is preserved. A greater weight-independent likelihood of diabetes remission after RYGB than LAGB suggests mechanisms beyond weight loss contribute to improved beta-cell function after RYGB. Trial Registration clinicaltrials.gov Identifier: NCT00465829.

During pregnancy, the rodent liver undergoes hepatocyte proliferation and increases in size, followed by weaning-induced involution via hepatocyte cell death and stromal remodeling, creating a prometastatic niche. These data suggest a mechanism for increased liver metastasis in breast cancer patients with recent childbirth. It is unknown whether the human liver changes in size and function during pregnancy and weaning. In this study, abdominal imaging was obtained in healthy women at early and late pregnancy and postwean. During pregnancy time points, glucose production and utilization and circulating bile acids were measured. Independently of weight gain, most women’s livers increased in size with pregnancy, then returned to baseline postwean. Putative roles for bile acids in liver growth and regression were observed. Together, the data support the hypothesis that the human liver is regulated by reproductive state with growth during pregnancy and volume loss postwean. These findings have implications for sex-specific liver diseases and for breast cancer outcomes.