Cumulative effect of obesity phenotypes on body weight and body mass index.

BACKGROUND: Obesity originates from an imbalance between energy intake and expenditure. Changes in energy intake components (satiation, postprandial satiety, emotional eating) and energy expenditure have been linked to obesity and are referred to as obesity phenotypes. We aim to study if these obesity phenotypes have a cumulative effect on body weight and body mass index (BMI). SUBJECT/METHODS: This is a cross-sectional study of adult patients with obesity (BMI > 30 kg/m2) who completed the validated tests to measure the obesity phenotypes. A total of 464 were included in this study. INTERVENTIONS/METHODS: We defined higher calories to fullness during an ad libitum meal as abnormal satiation, accelerated time to half gastric emptying with scintigraphy as abnormal postprandial satiety, higher anxiety score on the Hospital Anxiety and Depression Scale as hedonic eating behavior, and decreased percentage of measured resting energy expenditure as abnormal energy expenditure. The primary analysis was done on the number of phenotypes ( ≤ 1 and ≥ 2) with body weight and BMI using an independent t-test. RESULTS: Our cohort included 464 patients (mean [SD] age 42.0 [10.9] years, 79% females, weight 111.2 [22.9] kg, BMI 38.9 [7.0] kg/m2). There were 294 patients who had ≤ 1 phenotype, and 170 patients with ≥ 2 phenotypes with no baseline demographical differences (i.e., age and sex). Having ≥ 2 phenotypes was associated with higher body weight (115 [25] kg vs. 109 [21] kg; p = 0.004), BMI (40 [8] kg/m2 vs. 38 [7] kg/m2; p = 0.02) and waist (118 [15] cm vs. 115 [13] cm; p = 0.04) and hip (129 [14] cm vs. 125 [13] cm; p = 0.01) circumferences compared to ≤ 1 phenotype. CONCLUSION: Obesity phenotypes are associated with an additive effect on the body weight and BMI. Patients who have multiple obesity phenotypes may require a more aggressive approach to enhance weight loss.

Weight loss and cardiovascular disease risk outcomes of semaglutide: a one-year multicentered study.

BACKGROUND/OBJECTIVE: There are limited real-world studies assessing semaglutide weight loss and associated comorbidity and metabolic outcomes over periods ≥ 6 months. We aim to assess weight loss, metabolic, and cardiovascular outcomes of 12 months of semaglutide. SUBJECT/METHODS: We conducted a multicentered retrospective cohort study on semaglutide use. We included patients with a body-mass index (BMI) ≥ 27 kg/m2 who were prescribed weekly semaglutide subcutaneous injections. We excluded patients with bariatric surgeries, taking other anti-obesity medications, and with active malignancy or pregnancy. A total of 1023 patients had semaglutide prescription for obesity. INTERVENTION/METHODS: We assessed weight loss outcomes of subcutaneous semaglutide for 12 months. The primary endpoint was total body weight loss percentage (TBWL%) at 12 months. Secondary endpoints included proportion of patients achieving ≥5%, ≥10%, ≥15%, and ≥20% weight loss, and improvements in metabolic, cardiovascular, and comorbidities after 12 months of follow-up. RESULTS: We included 304 patients (73% female, 93% White, mean age 48.8 [12.4] years, BMI 40.9 [9.6] kg/m2) in the analysis. Patients achieved a TBWL of 13.4 (8.0)% at 12 months (p < 0.001 from baseline). Patients without T2DM achieved a TBWL of 16.9 (6.9)% compared to 9.9 (8.4)% in patients without T2DM at 12 months on the higher doses of semaglutide (p < 0.001 from baseline). In this cohort, 81% achieved ≥5%, 64% achieved ≥10%, 41% achieved ≥15%, and 22% achieved ≥20% TBWL at 12 months. Patients with overweight or obesity experienced significant improvements in metabolic, lipid profile, blood pressure, liver function tests, and cardiovascular disease risk outcomes. CONCLUSIONS: Semaglutide demonstrated notable improvement in obesity, metabolic, and cardiovascular disease risk outcomes in a clinical setting.

The association between previous use of anti-obesity medication and semaglutide weight loss outcomes.

AIMS: To compare weight loss outcomes between patients starting semaglutide who had previously been on another anti-obesity medication (AOM) compared to those who were AOM-naïve. MATERIALS AND METHODS: We performed a retrospective study in patients with overweight or obesity taking semaglutide for weight loss for a duration of 3 to 12 months. Our primary endpoint was assessment of percentage of total body weight loss (TBWL) in patients who started semaglutide as their first AOM (AOM-naïve) compared to those who started semaglutide and had previously taken another AOM (non-AOM-naïve). The secondary outcome was a comparison of the proportions of patients achieving ≥5%, ≥10%, ≥15% and ≥20% TBWL between the groups. Our endpoints were analysed using independent t-tests and ANOVA/ANCOVA for continuous variables and Pearson's test for categorical variables. RESULTS: This study included 305 patients. Outcomes of semaglutide treatment were superior in AOM-naïve patients (n = 231) compared to non-AOM-naïve patients (n = 74) at 3 (6.3% vs. 3.8%), 6 (10.6% vs. 6.7%), 9 (14.0% vs. 9.1%) and 12 months (14.3% vs. 10.6%; p < 0.0001 at 3, 6 and 9 months, and p = 0.01 at 12 months). A greater proportion of patients in the AOM-naïve group achieved a TBWL ≥ 15% (48% vs 21%; p = 0.02) and ≥20% (27% vs 4% p < 0.01) at 12 months. CONCLUSION: The use of semaglutide in patients with previous intake of other AOMs was associated with inferior weight loss outcomes in comparison to patients who were AOM-naïve.

Low Incidence of Pulmonary Aspiration During Upper Endoscopy in Patients Prescribed a Glucagon-Like Peptide 1 Receptor Agonist.

Glucagon-like peptide 1 (GLP-1) receptor agonists have transformed the treatment of type 2 diabetes and obesity. These agents have been associated with varying degrees of delay in gastric emptying, and a significant proportion of patients experience digestive side effects.1 There have been previous case reports of gastric retention of food and pulmonary aspiration during upper gastrointestinal (GI) endoscopy in the setting of GLP-1 receptor agonist use2; however, the cumulative incidence has not been previously explored.

Efficacy of Antiobesity Medications in Patients With Celiac Disease on a Gluten-free Diet: A Retrospective Matched Cohort Study.

GOALS: We aim to describe the weight loss outcomes of patients with celiac disease (CeD) taking antiobesity medications (AOMs) and compare it with the weight loss outcomes of patients without CeD taking AOMs. BACKGROUND: Increasing rates of obesity and obesity-associated comorbidities have been previously reported in patients with CeD on a gluten-free diet. The effectiveness of AOMs in this population has not been previously described. METHODS: In our retrospective cohort study, we matched 39 patients with treated CeD to 78 patients without CeD based on sex and AOM. We assessed the weight loss outcomes at 3, 6, and 12 months after starting the AOM in both cohorts and analyzed if there was a differential response when comparing by type of AOM [injectable glucagon-like peptide 1 (GLP-1) receptor agonists vs. oral non-GLP-1 AOMs]. RESULTS: Both cohorts had similar baseline demographic and anthropometric characteristics. At 12 months, the CeD cohort had a nonsignificantly inferior total body weight loss percentage compared with the cohort without CeD (6.5% vs. 9.5%, P=0.13). The CeD cohort had a similar proportion of patients achieving a total body weight loss percentage of ≥5% than the cohort without CeD (72.7% vs. 72.1%, P=1.00). No significant difference was observed when comparing the weight loss outcomes of injectables (GLP-1 receptor agonists) to oral AOMs. The proportion of patients reporting side effects was similar for both groups, regardless of the type of AOM. CONCLUSION: Patients with CeD taking AOMs had similar weight loss outcomes to patients without CeD. Hence, AOMs can be a safe and effective therapy for weight management in patients with CeD.

Weight-centric prevention of cancer.

Background: The link between excess adiposity and carcinogenesis has been well established for multiple malignancies, and cancer is one of the main contributors to obesity-related mortality. The potential role of different weight-loss interventions on cancer risk modification has been assessed, however, its clinical implications remain to be determined. In this clinical review, we present the data assessing the effect of weight loss interventions on cancer risk. Methods: In this clinical review, we conducted a comprehensive search of relevant literature using MEDLINE, Embase, Web of Science, and Google Scholar databases for relevant studies from inception to January 20, 2024. In this clinical review, we present systematic reviews and meta-analysis, randomized clinical trials, and prospective and retrospective observational studies that address the effect of different treatment modalities for obesity in cancer risk. In addition, we incorporate the opinions from experts in the field of obesity medicine and oncology regarding the potential of weight loss as a preventative intervention for cancer. Results: Intentional weight loss achieved through different modalities has been associated with a reduced cancer incidence. To date, the effect of weight loss on the postmenopausal women population has been more widely studied, with multiple reports indicating a protective effect of weight loss on hormone-dependent malignancies. The effect of bariatric interventions as a protective intervention for cancer has been studied extensively, showing a significant reduction in cancer incidence and mortality, however, data for the effect of bariatric surgery on certain specific types of cancer is conflicting or limited. Conclusion: Medical nutrition therapy, exercise, antiobesity medication, and bariatric interventions, might lead to a reduction in cancer risk through weight loss-dependent and independent factors. Further evidence is needed to better determine which population might benefit the most, and the amount of weight loss required to provide a clinically significant preventative effect.

Weight loss outcomes with semaglutide based on diabetes severity using the individualized metabolic surgery score.

Background: Semaglutide demonstrated inferior weight loss responses in patients with type 2 diabetes (T2D) compared to patients with obesity without T2D. The individualized metabolic surgery (IMS) score was validated to predict T2D remission after bariatric surgery. The parameters of the IMS are HbA1c (<7%), insulin use, T2D medications and T2D duration. We aim to assess weight loss outcomes of semaglutide based on IMS score in patients with obesity and T2D. Methods: This is a retrospective multicentered cohort study of patients with T2D and BMI≥ 27 kg/m2 taking ≥1 mg of semaglutide recruited from January 2020 to December 2022. We excluded patients with a history of bariatric surgery or taking other anti-obesity medications. IMS was calculated at baseline and patients weight change was recorded at baseline, 3, 6, 9 and 12 months. IMS was classified as mild (0-24.9 points), moderate (25-94.9 points), and severe (95-180 points). Analysis was performed based on IMS score quartiles and combination of Mild-Moderate vs Severe categories. We performed mixed linear regression models including age, sex, and baseline weight to assess associations between IMS categories with total body weight loss percentage (TBWL%). Findings: We included 297 patients (42% female, mean age 62 ± 12 years) in the analysis. At 12 months, there was a stepwise decrease in weight loss outcomes when comparing patients by IMS quartiles (LS mean TBWL%± SE): 8.8 ± 0.8% vs 6.9 ± 0.8% vs 5.7 ± 0.9% vs 5.0 ± 0.8%. In the mixed linear model, patients in the mild-moderate category achieved significantly superior weight loss outcomes (LS mean TBWL± SE: -8.3 ± 0.7%) than patients in the severe category (-5.5 ± 0.6%; difference: -2.9, 95% CI: -5.2 to -0.5, p = 0.006) at 12 months. There was no significant difference in glycemic improvement regardless of IMS severity at baseline. Interpretation: In our cohort, lower IMS severity was associated with more weight loss in patients with obesity and T2D. Further studies are needed to understand T2D severity and its effect on semaglutide outcomes. Funding: Beyond payment to the research staff by Mayo Clinic, this research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Weight loss response to semaglutide in postmenopausal women with and without hormone therapy use.

OBJECTIVE: To compare weight loss response and changes in cardiometabolic risk markers in postmenopausal women using semaglutide with and without menopause hormone therapy (HT) use. METHODS: Retrospective cohort study of postmenopausal women treated with semaglutide for overweight or obesity for ≥3 months. Endpoints: total body weight loss percentage (TBWL%) at 3, 6, 9, and 12 months after semaglutide initiation; and percentage of women achieving ≥5% and ≥10% TBWL and changes in cardiometabolic risk markers (glucose, blood pressure, and lipids) at 12 months. RESULTS: There were 16 women on HT and 90 on no-HT; mean age 56 ± 8 vs 59 ± 8 yr, P = 0.2 and mean BMI 36 ± 5 vs 39 ± 8 kg/m 2 , P = 0.1; respectively. Among women on no-HT, White race, dyslipidemia, and depression were more prevalent. Women on HT had a higher TBWL% at 3, 6, 9, and 12 months: 7 ± 3% vs 5 ± 4%, P = 0.01; 13 ± 6% vs 9 ± 5%, P = 0.01; 15 ± 6% vs 10 ± 6%, P = 0.02; and 16 ± 6% vs 12 ± 8%, P = 0.04; respectively. After adjusting for potential confounders, this association remained significant across time. At 12 months, a greater percentage of women on HT achieved ≥5% and ≥10% TBWL. Both groups experienced an improvement in cardiometabolic risk markers. CONCLUSION: In postmenopausal women with overweight or obesity treated with semaglutide, HT use was associated with an improved weight loss response. This association was maintained when adjusted for confounders. Larger studies should be conducted to confirm these results.

Unraveling the Variability of Human Satiation: Implications for Precision Obesity Management.

Satiation is the physiologic process that regulates meal size and termination, and it is quantified by the calories consumed to reach satiation. Given its role in energy intake, changes in satiation contribute to obesity's pathogenesis. Our study employed a protocolized approach to study the components of food intake regulation including a standardized breakfast, a gastric emptying study, appetite sensation testing, and a satiation measurement by an ad libitummeal test. These studies revealed that satiation is highly variable among individuals, and while baseline characteristics, anthropometrics, body composition and hormones, contribute to this variability, these factors do not fully account for it. To address this gap, we explored the role of a germline polygenic risk score, which demonstrated a robust association with satiation. Furthermore, we developed a machine-learning-assisted gene risk score to predict satiation and leveraged this prediction to anticipate responses to anti-obesity medications. Our findings underscore the significance of satiation, its inherent variability, and the potential of a genetic risk score to forecast it, ultimately allowing us to predict responses to different anti-obesity interventions.

Type 2 Diabetes Remission in Patients with Heterozygous Variants in the Leptin-Melanocortin Pathway after Roux-en-Y Gastric Bypass: A Matched Case-Control Study.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) is associated with a high rate of type 2 diabetes (T2D) remission. Carriers of heterozygous variants in the leptin-melanocortin pathway (LMP) are more likely to experience weight recurrence after RYGB. Our aim was to investigate if carrier status and associated weight regain affects the rate of T2D remission after RYGB. METHODS: Carriers of LMP variants with a diagnosis of T2D prior to RYGB (N = 16) were matched to non-carriers (N = 32) based on sex, age, and BMI. We assessed for post-operative T2D remission status post-surgery on a yearly basis, for up to 15 years. Our primary endpoint was the proportion of patients achieving T2D remission at 1 year. We conducted a survival analysis for all patients that achieved remission at least at one time-point to evaluate for maintenance of T2D remission by using a log-rank test. RESULTS: Both carriers and non-carriers had similar baseline and procedural characteristics. The proopiomelanocortin gene in the LMP pathway had the most variants (n = 5, 31%). Carriers had a lower total body weight loss percentage at nadir (28.7% ± 6.9) than non-carriers (33.7% ± 8.8, p = 0.04). The proportion of patients achieving T2D remission at 1 year was 68.8% for carriers and 71.9% for non-carriers (p = 1.0). Survival curves for maintenance of first remission were similar for both groups (p = 0.73), with a median survival of 8 years for both carriers and non-carriers. CONCLUSIONS: Despite inferior weight loss outcomes at nadir, carriers had similar T2D remission rates when compared to non-carriers. Weight-independent metabolic benefits of RYGB might contribute to this observation.

Scientific literacy and preferred resources used by Latin American medical students during the COVID-19 pandemic: A multinational survey.

Background: This study aims to identify the preferred sources for acquiring knowledge about COVID-19 and to evaluate basic knowledge on critical scientific literature appraisal in students from medical schools located in Spanish speaking countries in Latin America.  Methods: We designed an online survey of 15 closed-ended questions related to demographics, preferred resources for COVID-19 training, and items to assess critical appraisal skills. A snowball method was used for sampling. We conducted a descriptive analysis and Chi-squared tests to compare the proportion of correct identification of the concept of a preprint and a predatory journal when considering a) self-perceived level of knowledge, b) public vs private school, c) inclusion of a scientific literature appraisal subject in the curriculum, and d) progress in medical school. Results: Our sample included 770 valid responses, out of which most of the participants included were from Mexico (n=283, 36.8%) and Ecuador (n=229, 29.7%). Participants preferred using evidence-based clinical resources (EBCRs) to learn more about COVID-19 (n=182, 23.6%). The preferred study design was case report/series (n=218, 28.1%). We found that only 265 participants correctly identified the concept of a preprint (34.4%), while 243 students (31.6%) correctly identified the characteristics of a predatory journal. We found no significant differences in the proportion of correct answers regardless of the self-perceived level of knowledge, progress in medical school, or scientific literature critical appraisal classes. Conclusion: This study is novel in its approach of identifying sources of knowledge used by Latin American medical students and provides insights into the need to reinforce training in critical appraisal of scientific literature during medical school.

Publication rate and citation counts for preprints released during the COVID-19 pandemic: the good, the bad and the ugly.

BACKGROUND: Preprints are preliminary reports that have not been peer-reviewed. In December 2019, a novel coronavirus appeared in China, and since then, scientific production, including preprints, has drastically increased. In this study, we intend to evaluate how often preprints about COVID-19 were published in scholarly journals and cited. METHODS: We searched the iSearch COVID-19 portfolio to identify all preprints related to COVID-19 posted on bioRxiv, medRxiv, and Research Square from January 1, 2020, to May 31, 2020. We used a custom-designed program to obtain metadata using the Crossref public API. After that, we determined the publication rate and made comparisons based on citation counts using non-parametric methods. Also, we compared the publication rate, citation counts, and time interval from posting on a preprint server to publication in a scholarly journal among the three different preprint servers. RESULTS: Our sample included 5,061 preprints, out of which 288 were published in scholarly journals and 4,773 remained unpublished (publication rate of 5.7%). We found that articles published in scholarly journals had a significantly higher total citation count than unpublished preprints within our sample (p < 0.001), and that preprints that were eventually published had a higher citation count as preprints when compared to unpublished preprints (p < 0.001). As well, we found that published preprints had a significantly higher citation count after publication in a scholarly journal compared to as a preprint (p < 0.001). Our results also show that medRxiv had the highest publication rate, while bioRxiv had the highest citation count and shortest time interval from posting on a preprint server to publication in a scholarly journal. CONCLUSIONS: We found a remarkably low publication rate for preprints within our sample, despite accelerated time to publication by multiple scholarly journals. These findings could be partially attributed to the unprecedented surge in scientific production observed during the COVID-19 pandemic, which might saturate reviewing and editing processes in scholarly journals. However, our findings show that preprints had a significantly lower scientific impact, which might suggest that some preprints have lower quality and will not be able to endure peer-reviewing processes to be published in a peer-reviewed journal.

Quantifying alcohol use among Ecuadorian human immunodeficiency virus positive individuals and assessing alcohol as an independent risk factor for human immunodeficiency virus: A case control study STROBE.

Alcohol abuse has been identified as a risk factor for contracting human immunodeficiency virus (HIV) and accelerating disease progression. Our study aims to determine alcohol consumption rates among Ecuadorian HIV positive (HIV+) patients prior to diagnosis to evaluate its impact as an independent risk factor for contracting HIV. Additionally, we will examine post-diagnosis consumption rates among the HIV+ population.We provided anonymous questionnaires to 300 HIV+ patients and 600 internal medicine patients at 3 hospitals in Quito, Ecuador. Questionnaires quantified alcohol usage prior to HIV diagnosis, at time of diagnosis, and post-diagnosis while accounting for other potential HIV risk factors. We then determined frequencies of alcohol consumption and confounding variables. Finally, we performed a multivariable logistic regression controlling for confounders to determine the statistical significance of alcohol consumption as an independent risk factor for HIV.Our results showed increased odds for contracting HIV among those who drank daily (OR 5.3, CI 2.0-14.0) and those who consumed 6 or more alcoholic beverages on days they drank (OR 5.0, CI 3.1-8.2). Through multivariable analysis, we found that abstaining from binge drinking was a protective factor with an OR 0.5 (0.3-0.96). The percentage of HIV+ patients abstaining from alcohol increased from 30% twelve months prior to diagnosis to 57% after diagnosis.Our results show that alcohol abuse significantly increases the risk of contracting HIV. We found that prior to diagnosis, HIV patients consistently drank more frequently and a greater amount than the control group. Alcohol use significantly decreased among HIV+ patients after diagnosis.