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Adipocyte mitochondrial respiration may influence metabolic fuel partitioning into oxidation versus storage, with implications for whole-body energy expenditure. Although insulin has been shown to influence mitochondrial respiration, the effects of dietary macronutrient composition have not been well characterized. The aim of this exploratory study was to test the hypothesis that a high-carbohydrate diet lowers the oxygen flux of adipocyte mitochondria ex vivo. Among participants in a randomized-controlled weight-loss maintenance feeding trial, those consuming a high-carbohydrate diet (60% carbohydrate as a proportion of total energy, n = 10) had lower rates of maximal adipose tissue mitochondrial respiration than those consuming a moderate-carbohydrate diet (40%, n = 8, p = 0.039) or a low-carbohydrate diet (20%, n = 9, p = 0.005) after 10 to 15 weeks. This preliminary finding may provide a mechanism for postulated calorie-independent effects of dietary composition on energy expenditure and fat deposition, potentially through the actions of insulin on fuel partitioning.

Levels of obesity and overweight are increasing globally, with affected individuals often experiencing health issues and reduced quality of life. The pathogenesis of obesity is complex and multifactorial, and effective solutions have been elusive. In this Viewpoint, experts in the fields of medical therapy, adipocyte biology, exercise and muscle, bariatric surgery, genetics, and public health give their perspectives on current and future progress in addressing the rising prevalence of obesity.

BACKGROUND Obese and malabsorptive patients have difficulty increasing serum 25-hydroxyvitamin D [25(OH)D] after taking vitamin D supplementation. Since 25(OH)D is more hydrophilic than vitamin D, we hypothesized that oral 25(OH)D supplementation is more effective in increasing serum 25(OH)D concentrations in these patients. OBJECTIVES We aimed to investigate the pharmacokinetics of oral 25-hydroxyvitamin D3 [25(OH)D3] and oral vitamin D3 in healthy participants with differing BMI and malabsorptive patients. METHODS A randomized, double-blind crossover trial was performed in 6 malabsorptive patients and 10 healthy participants who were given 900 µg of either vitamin D3 or 25(OH)D3 orally followed by a pharmacokinetic study (PKS). After ≥28 d from the first dosing, each participant returned to receive the other form of vitamin D and undergo another PKS. For each PKS, serum vitamin D3 and 25(OH)D3 were measured at baseline and at 2, 4, 6, 8, and 12 h and days 1, 2, 3, 7, and 14. Pharmacokinetic parameters were calculated. RESULTS Data were expressed as means ± SEMs. The PKS of 900 µg vitamin D3 revealed that malabsorptive patients had 64% lower AUC than healthy participants (1177 ± 425 vs. 3258 ± 496 ng · h/mL; P

Levels of obesity and overweight are increasing globally, with affected individuals often experiencing health issues and reduced quality of life. The pathogenesis of obesity is complex and multifactorial, and effective solutions have been elusive. In this Viewpoint, experts in the fields of medical therapy, adipocyte biology, exercise and muscle, bariatric surgery, genetics, and public health give their perspectives on current and future progress in addressing the rising prevalence of obesity.

The obesity pandemic continues unabated despite a persistent public health campaign to decrease energy intake (“eat less”) and increase energy expenditure (“move more”). One explanation for this failure is that the current approach, based on the notion of energy balance, has not been adequately embraced by the public. Another possibility is that this approach rests on an erroneous paradigm. A new formulation of the energy balance model (EBM), like prior versions, considers overeating (energy intake > expenditure) the primary cause of obesity, incorporating an emphasis on “complex endocrine, metabolic, and nervous system signals” that control food intake below conscious level. This model attributes rising obesity prevalence to inexpensive, convenient, energy-dense, “ultra-processed” foods high in fat and sugar. An alternative view, the carbohydrate-insulin model (CIM), proposes that hormonal responses to highly processed carbohydrates shift energy partitioning toward deposition in adipose tissue, leaving fewer calories available for the body’s metabolic needs. Thus, increasing adiposity causes overeating to compensate for the sequestered calories. Here, we highlight robust contrasts in how the EBM and CIM view obesity pathophysiology and consider deficiencies in the EBM that impede paradigm testing and refinement. Rectifying these deficiencies should assume priority, as a constructive paradigm clash is needed to resolve long-standing scientific controversies and inform the design of new models to guide prevention and treatment. Nevertheless, public health action need not await resolution of this debate, as both models target processed carbohydrates as major drivers of obesity.

Introduction Obesity is a chronic illness that requires a multifaceted personalized treatment approach. Methods & Findings Using current guidelines and recent studies in weight management, this article reviews the multiple components of weight management: lifestyle intervention (dietary intervention, physical activity, and behavioral interventions), pharmacotherapy, endoscopic procedures, and surgical procedures. This review briefly discusses specific diets and dietary strategies, compensatory mechanisms acting against weight loss, recent changes to Food and Drug Administration approved antiobesity medications, and technological advances in weight management delivery. Conclusion Current literature is lacking large studies on the safety and efficacy of combination therapies involving pharmacotherapy plus 1 or more procedures.

Purpose of Review A growing body of evidence suggests that obesity and increased visceral adiposity are strongly and independently linked to adverse outcomes and death due to COVID-19. This review summarizes current epidemiologic data, highlights pathogenetic mechanisms on the association between excess body weight and COVID-19, compares data from previous pandemics, discusses why COVID-19 challenges the “obesity paradox,” and presents implications in prevention and treatment as well as future perspectives. Recent Findings Data from meta-analyses based on recent observational studies have indicated that obesity increases the risks of infection from SARS-CoV-2, severe infection and hospitalization, admission to the ICU and need of invasive mechanical ventilation (IMV), and the risk of mortality, particularly in severe obesity. The risks of IMV and mortality associated with obesity are accentuated in younger individuals (age ≤ 50 years old). The meta-inflammation in obesity intersects with and exacerbates underlying pathogenetic mechanisms in COVID-19 through the following mechanisms and factors: (i) impaired innate and adaptive immune responses; (ii) chronic inflammation and oxidative stress; (iii) endothelial dysfunction, hypercoagulability, and aberrant activation of the complement; (iv) overactivation of the renin–angiotensin–aldosterone system; (v) overexpression of the angiotensin-converting enzyme 2 receptor in the adipose tissue; (vi) associated cardiometabolic comorbidities; (vii) vitamin D deficiency; (viii) gut dysbiosis; and (ix) mechanical and psychological issues. Summary Mechanistic and large epidemiologic studies using big data sources with omics data exploring genetic determinants of risk and disease severity as well as large randomized controlled trials (RCTs) are necessary to shed light on the pathways connecting chronic subclinical inflammation/meta-inflammation with adverse COVID-19 outcomes and establish the ideal preventive and therapeutic approaches for patients with obesity.

Objective To determine the association between vitamin D status and morbidity and mortality in adult hospitalized coronavirus disease 2019 (COVID-19) patients Methods We performed a retrospective chart review study in COVID-19 patients aged ≥18 year hospitalized at Boston University Medical Center between March 1 and August 4, 2020. All studied patients tested positive for COVID-19 and had serum levels of 25-hydroxyvitamin D (25[OH]D) results measured within 1 year prior to the date of positive tests. Medical information was retrieved from the electronic medical record and was analyzed to determine the association between vitamin D status and hospital morbidity and mortality. Results Among the 287 patients, 100 (36%) were vitamin D sufficient (25[OH]D >30 ng/mL) and 41 (14%) died during hospitalization. Multivariate analysis in patients aged ≥65 years revealed that vitamin D sufficiency (25[OH]D ≥30 ng/mL) was statistically significantly associated with decreased odds of death (adjusted OR 0.33, 95% CI, 0.12-0.94), acute respiratory distress syndrome (adjusted OR 0.22, 95% CI, 0.05-0.96), and severe sepsis/septic shock (adjusted OR 0.26, 95% CI, 0.08-0.88), after adjustment for potential confounders. Among patients with body mass index Conclusion We revealed an independent association between vitamin D sufficiency defined by serum 25(OH)D ≥30 ng/mL and decreased risk of mortality from COVID-19 in elderly patients and patients without obesity.

Objective This study aimed to determine the medical cost impact and return on investment (ROI) of a large, commercial, digital, weight-management intensive lifestyle intervention (ILI) program (Real Appeal). Methods Participants in this program were compared with a control group matched by age, sex, geographic region, health risk, baseline medical costs, and chronic conditions. Medical costs were defined as the total amount paid for all medical expenses, inclusive of both the insurers' and the study participants' responsibility. Results In the 3 years following program registration, the intent-to-treat (ITT) cohort had significantly lower medical expenditures than the matched controls, with an average of -$771 or 12% lower costs (P = 0.002). Among 4,790 ITT participants, a total savings of $3,693,090 compared with total program costs of $1,639,961 translated into a 2.3:1 ROI. Program completers (n = 3,990), who attended more sessions than the overall ITT group, had greater mean weight loss (-4.4%), greater cost savings (-$956 or 14%), and an ROI of 2.0:1 over the 3-year time frame compared with matched controls. Conclusions The findings demonstrated that the digital weight-management ILI was associated with a significantly positive ROI. Employers and payers willing to cover the cost of an ILI that produces both weight loss and demonstrated cost benefits can improve health and save money for their population with overweight or obesity.

The obesity pandemic continues unabated despite a persistent public health campaign to decrease energy intake ("eat less") and increase energy expenditure ("move more"). One explanation for this failure is that the current approach, based on the notion of energy balance, has not been adequately embraced by the public. Another possibility is that this approach rests on an erroneous paradigm. A new formulation of the energy balance model (EBM), like prior versions, considers overeating (energy intakeexpenditure) the primary cause of obesity, incorporating an emphasis on "complex endocrine, metabolic, and nervous system signals" that control food intake below conscious level. This model attributes rising obesity prevalence to inexpensive, convenient, energy-dense, "ultra-processed" foods high in fat and sugar. An alternative view, the carbohydrate-insulin model (CIM), proposes that hormonal responses to highly processed carbohydrates shift energy partitioning toward deposition in adipose tissue, leaving fewer calories available for the body's metabolic needs. Thus, increasing adiposity causes overeating to compensate for the sequestered calories. Here, we highlight robust contrasts in how the EBM and CIM view obesity pathophysiology and consider deficiencies in the EBM that impede paradigm testing and refinement. Rectifying these deficiencies should assume priority, as a constructive paradigm clash is needed to resolve long-standing scientific controversies and inform the design of new models to guide prevention and treatment. Nevertheless, public health action need not await resolution of this debate, as both models target processed carbohydrates as major drivers of obesity.

OBJECTIVE Massive weight loss leads to marked knee pain reduction in individuals with knee pain, but the reason for the reduction in pain is unknown. This study was undertaken to quantify the contribution of magnetic resonance imaging (MRI)-evidenced changes in pain-sensitive structures, bone marrow lesions (BMLs), and synovitis, and changes in pain sensitization or depressive symptoms, to knee pain improvement after substantial weight loss. METHODS Morbidly obese patients with knee pain on most days were evaluated before bariatric surgery or medical weight management and at 1-year follow-up for BMLs and synovitis seen on MRI, the pressure pain threshold (PPT) at the patella and the right wrist, depressive symptoms (using the Center for Epidemiologic Studies Depression scale [CES-D]), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain survey. Natural-effects models were used to quantify the extent that achieving a minimum clinically important difference (MCID) of ≥18% on the WOMAC pain scale could be mediated by weight loss-induced changes in BMLs, synovitis, PPT, and depressive symptoms. RESULTS Of 75 participants, 53.3% lost ≥20% of weight by 1 year. Of these, 75% attained the MCID for pain improvement, compared with 34.3% in those who had

To examine whether depression status before metabolic and bariatric surgery (MBS) influenced 5-year weight loss, diabetes, and safety/utilization outcomes in the PCORnet Bariatric Study.Research on the impact of depression on MBS outcomes is inconsistent with few large, long-term studies.Data were extracted from 23 health systems on 36,871 patients who underwent sleeve gastrectomy (SG; n=16,158) or gastric bypass (RYGB; n=20,713) from 2005-2015. Patients with and without a depression diagnosis in the year prior to MBS were evaluated for % total weight loss (%TWL), diabetes outcomes, and postsurgical safety/utilization (reoperations, revisions, endoscopy, hospitalizations, mortality) at 1, 3 and 5 years after MBS.27.1% of SG and 33.0% of RYGB patients had preoperative depression, and they had more medical and psychiatric comorbidities than those without depression. At 5 years of follow-up, those with depression, versus those without depression, had slightly less %TWL after RYGB, but not after SG (between group difference = 0.42%TWL, p=0.04). However, patients with depression had slightly larger HbA1c improvements after RYGB but not after SG (between group difference = -0.19, p=0.04). Baseline depression did not moderate diabetes remission or relapse, reoperations, revision, or mortality across operations; however, baseline depression did moderate the risk of endoscopy and repeat hospitalization across RYGB versus SG.Patients with depression undergoing RYGB and SG had similar weight loss, diabetes, and safety/utilization outcomes to those without depression. The effects of depression were clinically small compared to the choice of operation.

Adipocyte mitochondrial respiration may influence metabolic fuel partitioning into oxidation versus storage, with implications for whole-body energy expenditure. Although insulin has been shown to influence mitochondrial respiration, the effects of dietary macronutrient composition have not been well characterized. The aim of this exploratory study was to test the hypothesis that a high-carbohydrate diet lowers the oxygen flux of adipocyte mitochondria ex vivo. Among participants in a randomized-controlled weight-loss maintenance feeding trial, those consuming a high-carbohydrate diet (60% carbohydrate as a proportion of total energy, n = 10) had lower rates of maximal adipose tissue mitochondrial respiration than those consuming a moderate-carbohydrate diet (40%, n = 8, p = 0.039) or a low-carbohydrate diet (20%, n = 9, p = 0.005) after 10 to 15 weeks. This preliminary finding may provide a mechanism for postulated calorie-independent effects of dietary composition on energy expenditure and fat deposition, potentially through the actions of insulin on fuel partitioning.

A role for fat overfeeding in metabolic dysfunction in humans is commonly implied in the literature. Comparatively less is known about acute carbohydrate overfeeding (COF). We tested the hypothesis that COF predisposes to oxidative stress by channeling electrons away from antioxidants to support energy storage. In a study of 24 healthy human subjects with and without obesity, COF was simulated by oral administration of excess carbohydrates; a two-step hyperinsulinemic clamp was used to evaluate insulin action. The distribution of electrons between oxidative and reductive pathways was evaluated by the changes in the reduction potentials (Eh) of cytoplasmic (lactate, pyruvate) and mitochondrial (β-hydroxybutyrate, acetoacetate) redox couples. Antioxidant redox was measured by the ratio of reduced to oxidized glutathione. We used cross-correlation analysis to evaluate the relationships between the trajectories of Eh, insulin, glucose, and respiratory exchange during COF. DDIT3 and XBP1s/u mRNA were measured as markers of endoplasmic reticulum stress (ER stress) in adipose tissue before and after COF. Here, we show that acute COF is characterized by net transfer of electrons from mitochondria to cytoplasm. Circulating glutathione is oxidized in a manner that significantly cross-correlates with increasing insulin levels and precedes the decrease in cytoplasmic Eh. This effect is more pronounced in overweight individuals (OW). Markers of ER stress in subcutaneous fat are detectable in OW within 4 h. We conclude that acute COF contributes to metabolic dysfunction through insulin-dependent pathways that promote electron transfer to the cytoplasm and decrease antioxidant capacity. Characterization of redox during overfeeding is important for understanding the pathophysiology of obesity and type 2 diabetes. NEW & NOTEWORTHY Current principles assume that conversion of thermic energy to metabolically useful energy follows fixed rules. These principles ignore the possibility of variable proton uncoupling in mitochondria. Our study shows that the net balance of electron distribution between mitochondria and cytoplasm is influenced by insulin in a manner that reduces proton leakage during overfeeding. Characterization of the effects of insulin on redox balance is important for understanding obesity and insulin resistance.

To comprehensively investigate the association between obesity/high body mass index (BMI) and risk of Clostridioides difficile infection (CDI) using systematic review and meta-analysis.Potentially eligible studies were identified from Medline and EMBASE databases from inception to February 2021 using search strategy consisting of terms for "Body Mass Index" and "Clostridioides Difficile". We only included studies that consist of a group of individuals with CDI and another group without CDI. Then, the studies must report their BMI or history of obesity. Odds ratio (OR) and 95% CIs of the association between BMI status and CDI were retrieved from each study and combined using the generic inverse variance method. Funnel plot was used to assess publication bias.A total of 4609 articles were identified. After two rounds of systematic review, 17 studies met the eligibility criteria and were included into the meta-analysis. Pooled analysis showed that individuals with high BMI had a significantly decreased odds of CDI with the pooled OR of 0.88 (95% CI 0.80-0.97). This meta-analysis had high statistical heterogeneity with IThis meta-analysis revealed a significant negative association between BMI and CDI.

ImportanceBariatric surgery is the most effective treatment for severe obesity; yet it is unclear whether the long-term safety and comparative effectiveness of these operations differ across racial and ethnic groups.ObjectiveTo compare outcomes of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) across racial and ethnic groups in the National Patient-Centered Clinical Research Network (PCORnet) Bariatric Study.Design, Setting, and ParticipantsThis was a retrospective, observational, comparative effectiveness cohort study that comprised 25 health care systems in the PCORnet Bariatric Study. Patients were adults and adolescents aged 12 to 79 years who underwent a primary (first nonrevisional) RYGB or SG operation between January 1, 2005, and September 30, 2015, at participating health systems. Patient race and ethnicity included Black, Hispanic, White, other, and unrecorded. Data were analyzed from July 1, 2021, to January 17, 2022.ExposureRYGB or SG.OutcomesPercentage total weight loss (%TWL); type 2 diabetes remission, relapse, and change in hemoglobin A1c (HbA1c) level; and postsurgical safety and utilization outcomes (operations, interventions, revisions/conversions, endoscopy, hospitalizations, mortality, 30-day major adverse events) at 1, 3, and 5 years after surgery.ResultsA total of 36 871 patients (mean [SE] age, 45.0 [11.7] years; 29 746 female patients [81%]) were included in the weight analysis. Patients identified with the following race and ethnic categories: 6891 Black (19%), 8756 Hispanic (24%), 19 645 White (53%), 826 other (2%), and 783 unrecorded (2%). Weight loss and mean reductions in HbA1c level were larger for RYGB than SG in all years for Black, Hispanic, and White patients (difference in 5-year weight loss: Black, −7.6%; 95% CI, −8.0 to −7.1; P < .001; Hispanic, −6.2%; 95% CI, −6.6 to −5.9; P < .001; White, −5.9%; 95% CI, −6.3 to −5.7; P < .001; difference in change in year 5 HbA1c level: Black, −0.29; 95% CI, −0.51 to −0.08; P = .009; Hispanic, −0.45; 95% CI, −0.61 to −0.29; P < .001; and White, −0.25; 95% CI, −0.40 to −0.11; P = .001.) The magnitude of these differences was small among racial and ethnic groups (1%-3% of %TWL). Black and Hispanic patients had higher risk of hospitalization when they had RYGB compared with SG (hazard ratio [HR], 1.45; 95% CI, 1.17-1.79; P = .001 and 1.48; 95% CI, 1.22-1.79; P < .001, respectively). Hispanic patients had greater risk of all-cause mortality (HR, 2.41; 95% CI, 1.24-4.70; P = .01) and higher odds of a 30-day major adverse event (odds ratio, 1.92; 95% CI, 1.38-2.68; P < .001) for RYGB compared with SG. There was no interaction between race and ethnicity and operation type for diabetes remission and relapse.Conclusions and RelevanceVariability of the comparative effectiveness of operations for %TWL and HbA1c level across race and ethnicity was clinically small; however, differences in safety and utilization outcomes were clinically and statistically significant for Black and Hispanic patients who had RYGB compared with SG. These findings can inform shared decision-making regarding bariatric operation choice for different racial and ethnic groups of patients.

Key Points Question Is bariatric surgical weight loss intervention for obesity associated with microvascular and macrovascular outcomes, and are they differentially associated with sex, race, and metabolic status? Findings In 307 individuals with obesity who were followed up after bariatric surgery, the procedure was associated with significant weight loss and improvement in both macrovascular and microvascular function across subgroups of sex, race, and traditional metabolic syndrome. Biomarker assessment using high-sensitivity C-reactive protein plasma levels of greater than 2 mg/dL identified individuals with seemingly metabolically healthy obesity and low-grade inflammation who also derived microvascular benefit from weight loss surgery. Meaning These findings suggest that the beneficial effects of weight loss surgery extend broadly across sex, race, and certain metabolically healthy subgroups., This cohort study identifies variables associated with vascular remodeling after bariatric surgery and examines how sex, race, and metabolic status are associated with microvascular and macrovascular outcomes., Importance Bariatric surgical weight loss is associated with reduced cardiovascular mortality; however, the mechanisms underlying this association are incompletely understood. Objectives To identify variables associated with vascular remodeling after bariatric surgery and to examine how sex, race, and metabolic status are associated with microvascular and macrovascular outcomes. Design, Setting, and Participants This population-based longitudinal cohort included 307 individuals who underwent bariatric surgery. Participants were enrolled in the bariatric weight loss program at Boston Medical Center, a large, multi-ethnic urban hospital, with presurgical and postsurgical assessments. Data were collected from December 11, 2001 to August 27, 2019. Data were analyzed in September 2019. Exposure Bariatric surgery. Main Outcomes and Measures Flow-mediated dilation (FMD) and reactive hyperemia (RH) (as measures of macrovascular and microvascular function, respectively) and clinical variables were measured preoperatively at baseline and at least once postoperatively within 12 months of the bariatric intervention. Results A total of 307 participants with obesity (mean [SD] age, 42 [12] years; 246 [80%] women; 199 [65%] White; mean [SD] body mass index, 46 [8]) were enrolled in this study. Bariatric surgery was associated with significant weight loss and improved macrovascular and microvascular function across subgroups of sex, race, and traditional metabolic syndrome (mean [SD] pre- vs postsurgery weight: 126 [25] kg vs 104 [25] kg; P

Adherence to weight management treatments is suboptimal. The Gelesis Loss Of Weight (GLOW; NCT02307279) pivotal trial data were used to assess treatment adherence impact on weight loss. The primary objectives of the GLOW study were to assess the effects of an oral superabsorbent hydrogel (OSH) on weight loss (targeted difference of ≥ 3%) and ≥ 5% weight loss responder status in subjects with a body mass index of 27-40 kg/m2. A total of 436 subjects were randomized to 3 capsules twice per day of OSH or placebo taken with 500 mL (16 oz) of water before lunch and dinner while on a hypocaloric diet (-300 kcal/day) for 24 weeks. There were 172 OSH- and 152 placebo-treated subjects who completed the study. Capsules counted at each study visit every 2-4 weeks were used to calculate overall percent treatment adherence (PTA) after the final visit. The PTA impact on weight loss was assessed using ANCOVA models with baseline BMI, fasting glucose and sex as covariates. A logit model with the same covariates was also used to assess the impact of PTA ≥ 95% or < 95% in subjects who achieved ≥ 10% or < 10% weight loss at 24 weeks. In the OSH group, mean PTA for was 97.61% ± 4.68% (SD) ranging from 70% to 111%, and all but 1 subject had PTA ≥ 80%. A significant interaction of ≥ 5% weight loss responder status and PTA was found (P=0.039); therefore, separate ANCOVA models were fit. PTA predicted weight loss at week 24 among the OSH group ≥ 5% responders, but not the ≥ 5% non-responders. Also, a PTA increase of 1 day/week predicted an additional 3.5% weight loss (β = 0.-25 ± 0.11 SE, P=0.024). PTA did not predict weight loss in the placebo group. OSH-treated subjects with ≥ 95% PTA were 4 times more likely to achieve ≥ 10% weight loss compared to those with < 95% PTA (P=0.027, odds ratio=4.27, 95%CI=1.18 to 15.41). These findings suggest that OSH has a binary impact on the treated subjects rather than a uniform effect. Increased PTA during OSH treatment predicted increased weight loss in patients responding to therapy with ≥ 5% weight loss, and not in non-responders or the placebo group. Disclosure L. E. Urban: Employee; Self; Gelesis. C. Apovian: Board Member; Self; Abbott, Allergan plc, Gelesis, Novo Nordisk, Nutrisystem, Tivity Health, Xeno Bioscience, Zafgen, Inc. L. Aronne: Other Relationship; Self; Allurion, Eisai & Janssen Pharmaceuticals, ERX Pharmaceuticals, Gelesis, Jamieson Wellness, Myos Corp, Intellihealth Corp, Novo Nordisk, Pfizer Foundation, Real Appeal, Research Support; Self; Astrazeneca, Aspire Bariatrics. H. Leider: Employee; Self; Gelesis.

There is a bidirectional association between hyperglycemia (HG) and COVID-19 severity. We conducted a retrospective cohort study in COVID-19 patients aged ≥18 years hospitalized at the Boston Medical Center during March 1 - August 4, 2020 with the aim to determine the relationships among HG, presence of type 2 diabetes (T2D) and outcomes of COVID-19. Blood glucose levels (BG) measured on admission were extracted from the hospital database. HG was defined as BG >200 mg/dL. Patients with type 1 diabetes or BG Disclosure N. Charoenngam: None. M. F. Holick: Consultant; Self; Biogena Inc, Ontometrics Inc, Other Relationship; Self; Quest Diagnostics, Speaker’s Bureau; Self; Abbott. C. Apovian: Board Member; Self; Abbott, Allergan plc, Gelesis, Novo Nordisk, Nutrisystem, Tivity Health, Xeno Bioscience, Zafgen, Inc. Funding National Institutes of Health (2T32DK7201-42 to N.C.), (P30DK046200 to C.A.)

Summary Introduction The elderly population is projected to be the fastest growing group of individuals with obesity group in the United States. As such, there is merit in examining factors that contribute to healthy aging and weight management. The effects of newer weight loss medications approved after 2013 have been studied but are not often assessed specifically in older persons. Methods This post hoc analysis evaluated the magnitude of weight loss in adults across age quartiles with lorcaserin, a serotonin (5‐HT) 2C receptor agonist indicated as an adjunct to a reduced‐caloric diet and increased physical activity for chronic weight management. Data from three lorcaserin pivotal phase 3 studies were used in this analysis. Data for patients with overweight/obesity without type 2 diabetes (T2D; BLOOM/BLOSSOM; body mass index [BMI] 27.0–29.9 kg/m2 and ≥1 comorbidity or BMI 30.0–45.0 kg/m2) and patients with overweight/obesity with T2D (BLOOM‐DM; BMI 27.0–45.0 kg/m2) were used. Patients were randomized to receive lorcaserin 10 mg twice daily or placebo in addition to diet and exercise for 52 weeks. Age quartiles between the studies differed as the T2D population was on average, 9 years older. Results This analysis shows that lorcaserin was associated with improved weight loss relative to placebo regardless of age. Importantly, these results were consistent for patients with and without T2D. Interestingly, the magnitude of weight loss for lorcaserin appeared to increase with increasing age. In patients without T2D, odds of achieving ≥5% and ≥10% reduction in body weight at 52 weeks were significantly higher for patients >36 years. Lorcaserin was well tolerated in all patients across all quartiles including the oldest quartile. Conclusions In summary, this post hoc analysis demonstrates that lorcaserin treatment in patients with and without T2D was safe and effective at reducing weight across all age groups analysed. Weight loss appeared to be greater for older patients; additional analyses are warranted to confirm these findings and to better understand the factors for improved weight loss.

Weight loss surgery (WLS) is neither risk-free nor universally effective. Few studies have examined what proportion of patients regret having undergone WLS.We interviewed patients at two WLS centers before and after WLS about weight loss, quality of life/QOL (Impact of Weight on QOL-lite), and decision regret (modified Brehaut Regret scale, range 0-100). We conducted separate multivariable logistic regression models to examine the association between weight loss and ∆QOL scores and having decision regret (score 50).Of 205 RYGB patients, only 2.2% (year 1) to 5.1% (year 4, n = 134) reported regret scores 50 over 4 years; 2.0-4.5% did not think they made the right decision; 2.0-4.5% would not undergo WLS again. In contrast, of 188 gastric banding patients (n = 123 at year 4), 8.2-20.3% had regret scores 50; 5.9-19.5% did not think they made the right decision; 7.1-19.5% would not undergo WLS again. Weight loss and ∆QOL scores were significant correlates of decision regret after banding although weight loss was a stronger correlate with lower model quasi-likelihood under the independence model criterion score. Four years after banding, mean weight loss for patients with regret scores 50 was 7.4% vs. 21.1% for those with scores 50; the AOR for regret score 50 was 0.90 (95% CI 0.87-0.94) for every 1% greater weight loss. Poor sexual function, but not weight loss or other QOL factors, was significantly correlated with decision regret after RYGB.Few patients regret undergoing RYGB but 20% regret undergoing gastric banding with weight loss being a major driver.

Background/objectives Prolonged-release (PR) naltrexone 32 mg/bupropion 360 mg (NB) is approved for chronic weight management as an adjunct to reduced-calorie diet and increased physical activity. Central nervous system-active medications have the potential to affect mood; therefore, post hoc analysis of clinical trial data was conducted to evaluate psychiatric adverse events (PAEs) and effects on mood of NB therapy versus placebo. Subjects/methods Data were pooled from 5 prospective, double-blind, randomized, placebo-controlled clinical trials (duration range, 24–56 weeks) of NB in subjects with overweight or obesity. PAEs were collected via AE preferred terms, organized into major subtopics (e.g., anxiety, depression, sleep disorders), and divided into category terms (e.g., anxiety, potential anxiety symptoms). Additionally, the Inventory of Depressive Symptomatology Self Report (IDS-SR; score range 0–84) and the Columbia Classification Algorithm of Suicide Assessment (C-CASA) evaluated treatment-emergent depressive/anxiety symptoms and suicidal behavior/ideation, respectively. Results Baseline characteristics and comorbidities were comparable for placebo (n = 1515) and NB (n = 2545). Most common PAEs in the NB group (using category grouping; NB vs placebo) were sleep disorders (12.7 vs 7.9%, P < 0.001), anxiety (5.4 vs 3.3%, P = 0.029), and depression (1.8 vs 2.7%, P = 0.014); PAEs were more frequent during dose escalation and generally mild or moderate. Mean (SD) changes in IDS-SR total score from baseline to endpoint were small in both groups: 0.13 (5.83) for NB and −0.45 (5.65) for placebo. Retrospective AE categorization via C-CASA confirmed no completed suicides, suicide attempts, or preparatory acts toward imminent suicidal behavior. Conclusions This large pooled analysis of 5 clinical trials provides additional safety information about the NB PAE profile. Anxiety and sleep disorder-related PAEs were more frequent with NB versus placebo but were mostly mild to moderate and generally occurred early. Depression-related PAEs were less common with NB than placebo, and NB was not associated with suicidal ideation or behavior in this patient population.

A safety-net hospital in Boston, Massachusetts, made adaptations to its Nourishing Our Community Program to accommodate restrictions brought on by the COVID-19 pandemic to continue providing food and education to patients. While participation in programs decreased overall, some of the adaptations made, including virtual classes and food pantry home delivery, were well received and are planned to be maintained after the pandemic subsides. By making adjustments to operational procedures, the Nourishing Our Community Program continued to reach its underserved population despite pandemic challenges.

Background Black individuals have been disproportionately affected by the coronavirus disease 2019 (COVID-19). However, it remains unclear whether there are any biological factors that predispose Black patients to COVID-19-related morbidity and mortality. Objective To compare in-hospital morbidity, mortality, and inflammatory marker levels between Black and White hospitalized COVID-19 patients. Design and Participants This single-center retrospective cohort study analyzed data for Black and White patients aged ≥18 years hospitalized with a positive SARS-CoV-2 PCR test between March 1, 2020, and August 4, 2020. Main Measures The exposure was self-identified race documented in the medical record. The primary outcome of was in-hospital death. Secondary outcomes included intensive care unit admission, hospital morbidities, and inflammatory marker levels. Key Results A total of 1,424 Black and White patients were identified. The mean ± SD age was 56.1 ± 17.4 years, and 663 (44.5%) were female. There were 683 (48.0%) Black and 741 (52.0%) White patients. In the univariate analysis, Black patients had longer hospital stays (8.1 ± 10.2 vs. 6.7 ± 8.3 days, p = 0.011) and tended to have higher rates of in-hospital death (11.0% vs. 7.3%), myocardial infarction (6.9% vs. 4.5%), pulmonary embolism (PE; 5.0% vs. 2.3%), and acute kidney injury (AKI; 39.4% vs. 23.1%) than White patients (p

Objective This study aimed to explore the relationship between an obesity diagnosis and weight loss as a percentage of total body weight loss over 9 to 15 months, using electronic health record data. Methods An observational study of 688,878 adult patients at 15 health systems with BMI ≥ 30 kg/m2 examined the relationship between weight loss and documentation of obesity diagnosis. Multivariable logistic regression models were created using a stepwise backwards elimination procedure to identify potential predictors of weight loss. Results Of patients with BMI ≥ 30, 44.9% had an obesity diagnosis on a claim or electronic health record problem list; 16.9% and 5.9% lost ≥ 5% and ≥ 10% of their body weight, respectively. Multivariable logistic regression models revealed a diagnosis of obesity on the same day as the initial weight (odds ratio [OR] = 1.3; CI: 1.2‐1.3; P

Background It remains controversial whether high protein diets improve cardiometabolic profile. We investigated whether increasing protein intake to 1.3 g/kg/day in functionally limited older adults with usual protein intake ≤RDA (0.8 g/kg/day) improves visceral fat accumulation and serum cardiovascular risk markers more than the recommended daily allowance (RDA). Methods The Optimizing Protein Intake in Older Men Trial was a placebo-controlled, randomized trial in which 92 functionally limited men, ≥65 years, with usual protein intake ≤RDA were randomized for 6 months to: 0.8 g/kg/day protein plus placebo; 1.3 g/kg/day protein plus placebo; 0.8 g/kg/day protein plus testosterone enanthate 100 mg weekly; or 1.3 g/kg/day protein plus testosterone enanthate 100 mg weekly. In this substudy, metabolic and inflammatory serum markers were measured in 77 men, and visceral adipose tissue (VAT) was assessed using dual-energy x-ray absorptiometry in 56 men. Results Treatment groups were similar in their baseline characteristics. Randomization to 1.3 g/kg/day protein group was associated with greater reduction in VAT compared to 0.8 g/kg/day group (between-group difference: −17.3 cm2, 95% confidence interval [CI]: −29.7 to −4.8 cm2, p = .008), regardless of whether they received testosterone or placebo. Changes in fasting glucose, fasting insulin, HOMA-IR, leptin, adiponectin, IL-6, and hs-CRP did not differ between the 0.8 versus 1.3 g/kg/day protein groups regardless of testosterone use. Conclusions Protein intake >RDA decreased VAT in functionally limited older men but did not improve cardiovascular disease risk markers. Clinical Trials Registration Number NCT01275365

Context Weight regain (WR) after bariatric surgery is emerging as a common clinical problem due to the increase in the number of procedures performed. Early interventions are necessary to curtail the potential recurrence of comorbid conditions. However, it is often difficult to recognize WR early enough to introduce mitigating measures because there are no current guidelines for timely diagnosis and assessment of the severity of this condition. Objective We present a practical approach for the early recognition of WR, based on 11-year follow-up data from our multiethnic bariatric surgery patient population. Methods We classify WR according to the rate of increase in weight relative to nadir weight, normalized per 30-day interval. We also review pertinent literature about the etiologic factors contributing to WR after bariatric surgery. Results According to our algorithm, mild, moderate, and rapid WR are defined as weight increases of 0.2% to Conclusion Our approach emphasizes the importance of regular long-term follow-up for all bariatric surgery patients.