Baseline Body Mass Index Category Research Articles

Association between Weight Changes over a 4-Year Period and Health-Related Quality of Life in Middle-Aged and Older Adults in Korea: The Korean Genome and Epidemiology Study Cohort.

The relationship between weight change and quality of life remains controversial. This study aimed to investigate whether changes in body weight among participants in different baseline body mass index categories are associated with physical and mental health functioning. We conducted an analysis involving 5,106 adults who participated in the Korean Genome and Epidemiology Study, a cohort comprising Korean adults aged 40 to 69 years. We categorized participants into three groups based on body weight change, and physical and mental health were assessed using the 12-Item Short-Form Health Survey in year 4. We employed logistic regression analysis to assess the association between body weight change and poor functioning at year 4. We also utilized a generalized estimating equation to determine the relationship between weight changes and mental component summary (MCS) scores over the study period for each weight group. Weight gain in both the normal weight (odds ratio [OR], 1.88; 95% confidence interval [CI], 1.13-3.11; P=0.01) and overweight groups (OR, 1.75; 95% CI, 1.05-2.91; P=0.03) was associated with poor MCS. Normal weight weight-losers were associated with a greater increase (2.69 points; 95% CI, 0.50-4.88) in MCS compared to weightmaintainers. Significant differences in mean MCS were observed for overweight weight-losers, obese weight-gainers, and underweight weight-gainers when compared to weight maintainers in each respective weight group. Different patterns of relationships between weight change and mental health-related quality of life were observed. Hence, it is crucial to focus on the mental health of middle-aged and older adults when assessing body weight changes.

Long-term weight loss effects of semaglutide in obesity without diabetes in the SELECT trial.

In the SELECT cardiovascular outcomes trial, semaglutide showed a 20% reduction in major adverse cardiovascular events in 17,604 adults with preexisting cardiovascular disease, overweight or obesity, without diabetes. Here in this prespecified analysis, we examined effects of semaglutide on weight and anthropometric outcomes, safety and tolerability by baseline body mass index (BMI). In patients treated with semaglutide, weight loss continued over 65 weeks and was sustained for up to 4 years. At 208 weeks, semaglutide was associated with mean reduction in weight (-10.2%), waist circumference (-7.7 cm) and waist-to-height ratio (-6.9%) versus placebo (-1.5%, -1.3 cm and -1.0%, respectively; P < 0.0001 for all comparisons versus placebo). Clinically meaningful weight loss occurred in both sexes and all races, body sizes and regions. Semaglutide was associated with fewer serious adverse events. For each BMI category (<30, 30 to <35, 35 to <40 and ≥40 kg m-2) there were lower rates (events per 100 years of observation) of serious adverse events with semaglutide (43.23, 43.54, 51.07 and 47.06 for semaglutide and 50.48, 49.66, 52.73 and 60.85 for placebo). Semaglutide was associated with increased rates of trial product discontinuation. Discontinuations increased as BMI class decreased. In SELECT, at 208 weeks, semaglutide produced clinically significant weight loss and improvements in anthropometric measurements versus placebo. Weight loss was sustained over 4 years. ClinicalTrials.gov identifier: NCT03574597 .

Body Weight Variability and Risk of Suicide Mortality: A Nationwide Population-Based Study

Background. Suicide is a pressing global health concern, and identifying its risk factors is crucial for prevention. Body weight variability (BWV) has been increasingly recognized as a potential factor impacting physical and mental health outcomes. We aimed to explore the relationship between BWV and the risk of suicide mortality using a nationally representative database. Methods. This population-based cohort study used data from the Korean National Health Insurance Database and included a total of 1,983,701 subjects. BWV was assessed using at least three health examination datasets and validated variability indices (variability independent of the mean (VIM), average successive variability, and coefficient of variation), and patients were divided into BWV quartiles (Q1–Q4). The primary endpoint was suicide-related death. Results. During a median of 11.3 years of follow-up, 5,883 suicide deaths occurred. A higher baseline body weight was associated with a lower risk of suicide. However, greater BWV (VIM) was associated with a significantly greater risk of suicide (adjusted hazard ratio [95% confidence interval], 1.35 [1.26–1.45] in the Q4 group), even after adjusting for baseline body mass index (BMI). Similar results were observed regardless of obesity or BMI category. Consistent findings were observed when using different variability indices. Subgroup analyses according to sex, age, diabetes, and depression also supported these findings. Conclusion. Our study highlights the importance of considering BWV as a potential risk factor for suicide.

Body mass index and cardiorenal outcomes in the EMPEROR-Preserved trial: Principal findings and meta-analysis with the DELIVER trial.

Both low and high body mass index (BMI) are associated with poor heart failure outcomes. Whether BMI modifies benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in heart failure with preserved ejection fraction (HFpEF) requires further investigation. Using EMPEROR-Preserved data, the effects of empagliflozin versus placebo on the risks for the primary outcome (hospitalization for heart failure [HHF] or cardiovascular [CV] death), change in estimated glomerular filtration rate (eGFR) slopes, change in Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS), and secondary outcomes across baseline BMI categories (<25 kg/m2, 25 to <30 kg/m2, 30 to <35 kg/m2, 35 to <40 kg/m2 and ≥40 kg/m2) were examined, and a meta-analysis conducted with DELIVER. Forty-five percent had a BMI of ≥30 kg/m2. For the primary outcome, there was a consistent treatment effect of empagliflozin versus placebo across the BMI categories with no formal interaction (p trend = 0.19) by BMI categories. There was also no difference in the effects on secondary outcomes including total HHF (p trend = 0.19), CV death (p trend = 0.20), or eGFR slope with slower declines with empagliflozin regardless of BMI (range 1.12-1.71 ml/min/1.73 m2 relative to placebo, p trend = 0.85 for interaction), though there was no overall impact on the composite renal endpoint. The difference in weight change between empagliflozin and placebo was -0.59, -1.48, -1.54, -0.87, and - 2.67 kg in the lowest to highest BMI categories (p trend = 0.016 for interaction). A meta-analysis of data from EMPEROR-Preserved and DELIVER showed a consistent effect of SGLT2i versus placebo across BMI categories for the outcome of HHF or CV death. There was a trend toward greater absolute KCCQ-CSS benefit at 32 weeks with empagliflozin at higher BMIs (p = 0.08). Empagliflozin treatment resulted in broadly consistent cardiac effects across the range of BMI in patients with HFpEF. SGLT2i treatment yields benefit in patients with HFpEF regardless of baseline BMI.

Cross-sectional and longitudinal associations between self-esteem and BMI depends on baseline BMI category in a population-based study

BackgroundSome studies have reported associations between self-esteem and weight status, but longitudinal data on adults remain scarce. The aim of this population-based study was to analyze the cross-sectional and longitudinal association between self-esteem and body mass index (BMI) and to investigate whether baseline BMI has an impact on this association.MethodsIn 2016, 29,735 participants aged ≥ 18 years in the NutriNet-Santé cohort completed the Rosenberg Self-Esteem Scale. BMI was self-reported yearly over a 4-year period. Association between self-esteem and BMI was assessed using mixed models and logistic regressions. Analyses were stratified by BMI (categorical) at baseline and adjusted on sociodemographic and lifestyle characteristics.ResultsAt baseline, higher self-esteem was associated with higher BMI in normal weight individuals(p = 0.32), and with lower BMI in obese class II and III individuals (p = 0.13). In addition, higher baseline self-esteem was associated with BMI increase over time in normal weight individuals (p = 0.15). Among normal weight individuals, those with higher self-esteem were less likely to show a decrease in their BMI (p = 0.005), while no association was observed with BMI increase (p = 0.81).DiscussionOur findings suggest that the association between self-esteem and BMI depends on the initial category of BMI, with a negligible effect of self-esteem.

Efficacy, safety, and pharmacokinetics by BMI category in Phase 3/3b cabotegravir + rilpivirine long-acting trials.

Cabotegravir + rilpivirine (CAB + RPV) is a guideline-recommended long-acting (LA) injectable regimen for the maintenance of HIV-1 virologic suppression. This post hoc analysis summarizes CAB + RPV LA results by baseline body mass index (BMI) category among Phase 3/3b trial participants. Data from CAB + RPV-naive participants receiving every 4 or 8 week dosing in FLAIR, ATLAS, and ATLAS-2 M were pooled through Week (W) 48. Data beyond W48 were summarized by study (FLAIR through W96 and ATLAS-2 M through W152). HIV 1 RNA <50 and ≥50 copies/mL, confirmed virologic failure (CVF; two consecutive HIV-1 RNA ≥200 copies/mL), safety and tolerability, and plasma CAB and RPV trough concentrations were evaluated by baseline BMI (<30 kg/m2 [lower]; ≥ 30 kg/m2 [higher]). Among 1245 CAB + RPV LA participants, 213 (17%) had a baseline BMI ≥30 kg/m2. At W48, 92% vs. 93% of participants with lower vs. higher BMI had HIV-1 RNA <50 copies/mL, respectively. Including data beyond W48, 18 participants had CVF; those in the higher BMI group (n = 8) all had at least one other baseline factor associated with CVF (archived RPV resistance-associated mutations or HIV 1 subtype A6/A1). Safety and pharmacokinetic profiles were comparable between BMI categories. CAB + RPV LA was efficacious and well tolerated, regardless of baseline BMI category.Main point summary: CAB + RPV LA is effective in the maintenance of HIV-1 virologic suppression in adults regardless of BMI category, with longer-length needles (≥2 inches) recommend for those with BMI ≥30 kg/m2 to accommodate individual body habitus and ensure appropriate administration.

1985. A Prospective, Randomized Trial to Assess a Protease Inhibitor–based Regimen Switch Strategy to Manage Integrase Inhibitor–related Weight Gain

Abstract Background Integrase inhibitor (INI)–based antiretroviral (ARV) therapies are associated with greater weight gain than non-nucleoside reverse transcriptase inhibitor– or boosted protease inhibitor–based regimens, disproportionately affecting Black and Hispanic individuals and women. The mechanisms underlying this weight gain are unknown, and there are no prospective, randomized data exploring the impact of switching ARV classes to mitigate or reverse ARV-related weight gain. Methods DEFINE (ClinicalTrials.gov: NCT04442737) is a randomized (1:1), prospective, 48-week, active-controlled, open-label, multicenter phase 4 study evaluating switching to darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) versus continuing INI+TAF/emtricitabine (FTC) in virologically-suppressed HIV-1–infected adults who had ≥10% weight gain while on the INI-based regimen. The primary objective was to assess percent change in body weight from baseline to Week 24 in both arms. The primary endpoint was analyzed using a mixed model for repeated measures in the intent-to-treat set of randomized participants who had received ≥1 dose of study drug. Secondary endpoints included change in body mass index (BMI), waist circumference (WC), efficacy, and safety. Data through Week 24 are reported. Results Overall, 103 adults were randomized to D/C/F/TAF (n=53) or continued INI+TAF/FTC (n=50); 30% were female and 61% were Black/African American, with median 27.0 months virologic suppression on INI+TAF/FTC (Table 1). Discontinuation rates were low and similar between arms. At Week 24, there was no significant difference in percent change in body weight from baseline between the D/C/F/TAF and INI+TAF/FTC arms (Figure). Most participants in each arm had body weight changes of ≤±3% and remained within baseline BMI and WC categories. Percent body weight changes for key subgroups are shown in Table 2. Switching to D/C/F/TAF was safe and well tolerated, and efficacy was maintained.Table 1.Demographics and Baseline Characteristics (ITT Set)BMI, body mass index; D/C/F/TAF, darunavir/cobicistat/emtricitabine/tenofovir alafenamide; FTC, emtricitabine; INI, integrase inhibitor; ITT, intent-to-treat; TAF, tenofovir alafenamide. *One participant in the D/C/F/TAF arm did not have available data. Percent Change From Baseline in Body Weight Over Time for Participants Who Switched to D/C/F/TAF and Those Who Continued Their Current INI+TAF/FTC Regimen (ITT Set) D/C/F/TAF, darunavir/cobicistat/emtricitabine/tenofovir alafenamide; FTC, emtricitabine; INI, integrase inhibitor; ITT, intent-to-treat; LS, least-squares; TAF, tenofovir alafenamide. LS means percent changes in body weight were calculated in the ITT set of randomized participants who had received ≥1 dose of study drug using a mixed model for repeated measures, in which the dependent variable was percent change from baseline in body weight; independent variables were treatment, baseline body mass index, sex, and race (Black/African American vs non–Black/African American); and visits were repeated measures. Participants in the ITT set with baseline records and ≥1 postbaseline record were included. Conclusion There was no significant difference in weight change through 24 weeks after switching from an INI-based regimen to D/C/F/TAF in adults with INI-related weight gain. Additional analyses are ongoing, including follow up through Week 48 and evaluation of changes in biomarkers and body composition (DEXA).Table 2.Percent Change From Baseline in Body Weight at Week 24 Among Key Subgroups (ITT Set)BMI, body mass index; D/C/F/TAF, darunavir/cobicistat/emtricitabine/tenofovir alafenamide; FTC, emtricitabine; INI, integrase inhibitor; ITT, intent-to-treat; TAF, tenofovir alafenamide. Disclosures William R. Short, MD, Gilead Sciences: Advisor/Consultant|ViiV: Advisor/Consultant|ViiV: Honoraria Moti Ramgopal, MD, FACP, FIDSA, AbbVie: Honoraria|Gilead Sciences, Inc.: Advisor/Consultant|Gilead Sciences, Inc.: Honoraria|Janssen Pharmaceuticals: Advisor/Consultant|Janssen Pharmaceuticals: Honoraria|Merck: Advisor/Consultant|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Honoraria Debbie P. Hagins, MD, FAPCR, AAHIVS, Janssen Pharmaceuticals: Advisor/Consultant Johnnie Lee, MD, Janssen Pharmaceuticals: Employee|Janssen Pharmaceuticals: Stocks/Bonds Richard Bruce Simonson, BS, Janssen Pharmaceuticals: Employee|Janssen Pharmaceuticals: Stocks/Bonds Tien-Huei Hsu, PhD, Janssen Pharmaceuticals: Employee|Janssen Pharmaceuticals: Stocks/Bonds Ping Xu, PhD, Janssen Pharmaceuticals: Employee|Janssen Pharmaceuticals: Stocks/Bonds David Anderson, MD, Janssen Pharmaceuticals: Employee|Janssen Pharmaceuticals: Stocks/Bonds

The impact of COVID-19 lockdowns on the body mass index of people living with obesity: A UK retrospective cohort study using the UK Clinical Practice Research Datalink

BackgroundRestrictions implemented by governments during the coronavirus disease 2019 (COVID-19) pandemic affected people’s eating habits and physical activity. We investigated the effect of COVID-19 lockdowns and restrictions on body mass index (BMI) and weight in a UK population, according to BMI class, sex, age and ethnicity. MethodsThis retrospective observational cohort study used the Clinical Practice Research Datalink AURUM database. Baseline spanned from 22 March 2017–22 March 2020, and the follow-up lockdown period was from 23 March 2020 (start of the lockdown in the UK) to 13 March 2021. The descriptive analysis included individuals with ≥ 1 valid BMI/weight measurements during both the baseline and follow-up periods, while the model-based analysis comprised individuals with ≥ 1 valid measurement(s) during baseline. Results were stratified by baseline BMI category, sex, age and ethnicity. ResultsIn the descriptive analysis (n = 273,529), most individuals did not change BMI category post-lockdown (66.4–83.3%). A greater proportion of women (12.6%) than men (9.5%) moved up BMI categories post-lockdown. Compared with older groups, a higher proportion of individuals < 45 years old increased post-lockdown BMI category. The model-based analysis (n = 938,150) revealed consistent trends, where changes in body weight and BMI trajectories pre- and post-lockdown were observed for women and for individuals < 45 years. ConclusionDuring COVID-19 restrictions, women and young individuals were more likely than other groups to increase BMI category and weight post-lockdown.

Association of Body Weight With Response to Vitamin D Supplementation and Metabolism

In the Vitamin D and Omega-3 Trial (VITAL), the effects of randomized vitamin D supplementation (cholecalciferol), 2000 IU/d, reduced the risk of several health outcomes among participants with normal, but not elevated, body weights. It was unclear whether weight had any association with the outcomes of the supplementation. To investigate whether baseline body mass index (BMI) modifies vitamin D metabolism and response to supplementation. VITAL is a completed randomized, double-blind, placebo-controlled trial for the primary prevention of cancer and cardiovascular disease. In the present cohort study, an analysis was conducted in a subset of VITAL participants who provided a blood sample at baseline and a subset with a repeated sample at 2 years' follow-up. VITAL was conducted from July 1, 2010, to November 10, 2018; data analysis for the present study was conducted from August 1, 2021, to November 9, 2021. Treatment outcomes of vitamin D, 2000 IU/d, supplementation vs placebo associated with clinical and novel vitamin D-related biomarkers by BMI category adjusted for other factors associated with vitamin D status. Multivariable-adjusted means (SE) or 95% CIs of vitamin D-related serum biomarkers at baseline and follow-up: total 25-hydroxyvitamin D (25-OHD), 25-OHD3, free vitamin D (FVD), bioavailable vitamin D (BioD), vitamin D-binding protein (VDBP), albumin, parathyroid hormone (PTH), and calcium, and log-transformed as needed. A total of 16 515 participants (mean [SD] age, 67.7 [7.0] years; 8371 women [50.7%]; 12420 non-Hispanic White [76.9%]) were analyzed at baseline, including 2742 with a follow-up blood sample. Before randomization, serum total 25-OHD levels were incrementally lower at higher BMI categories (adjusted mean [SE]: underweight, 32.3 [0.7] ng/mL; normal weight, 32.3 [0.1] ng/mL; overweight, 30.5 [0.1] ng/mL; obesity class I, 29.0 [0.2] ng/mL; and obesity class II, 28.0 [0.2] ng/mL; P < .001 for linear trend). Similarly, baseline 25-OHD3, FVD, BioD, VDBP, albumin, and calcium levels were lower with higher BMI, while PTH level was higher (all P < .001 for linear trend). Compared with placebo, randomization to vitamin D supplementation was associated with an increase in total 25-OHD, 25-OHD3, FVD, and BioD levels compared with placebo at 2 years' follow-up, but increases were significantly lower at higher BMI categories (all treatment effect interactions P < .001). Supplementation did not substantially change VDBP, albumin, PTH, or calcium levels. In this randomized cohort study, vitamin D supplementation increased serum vitamin D-related biomarkers, with a blunted response observed for participants with overweight or obesity at baseline. These longitudinal findings suggest that BMI may be associated with modified response to vitamin D supplementation and may in part explain the observed diminished outcomes of supplementation for various health outcomes among individuals with higher BMI.

Weight change and clinical outcomes in heart failure with reduced ejection fraction: insights from EMPEROR-Reduced.

Baseline body mass index (BMI) and weight loss promoted by sodium-glucose cotransporter 2 inhibitors may impact outcomes in patients with heart failure with reduced ejection fraction (HFrEF). We assessed in the EMPEROR-Reduced population treated with empagliflozin versus placebo the relationship between baseline BMI, weight loss and effects on the primary (time to first hospitalization for heart failure [HHF] or cardiovascular death) and key secondary outcomes. We categorized patients according to their baseline BMI: <20 kg/m2 (n=180); 20 to <25 kg/m2 (n=1038); 25 to <30 kg/m2 (n=1345); 30 to <35 kg/m2 (n=774) and ≥35 kg/m2 (n=393). The treatment effect of empagliflozin on the primary outcome was consistent across all BMI categories (hazard ratios in subgroups 0.66-0.88, interaction trend p=0.32), as was the effect on total (first plus recurrent) HHF (interaction trend p=0.31). Empagliflozin reduced the rate of estimated glomerular filtration rate decline consistently across the BMI categories (interaction trend p=0.67). Overall, incidence rates of any or serious adverse events were comparable between the treatment groups across all BMI categories. A total of 313 (17.4%) patients treated with empagliflozin experienced a weight loss of more than 5% at week 52 versus 230 (12.8%) in placebo. When analysed separately within each treatment group, presence of weight loss was similarly associated with an increased risk of all-cause mortality. The benefits of empagliflozin versus placebo were consistently present across all BMI categories in HFrEF patients. Weight loss was associated with higher risk of all-cause mortality, regardless of treatment group.

Associations of body mass index (BMI) and BMI change with progression of chronic kidney disease in children.

Obesity is prevalent among children with chronic kidney disease (CKD) and is associated with cardiovascular disease and reduced quality of life. Its relationship with pediatric CKD progression has not been described. We evaluated relationships between both body mass index (BMI) category (normal, overweight, obese) and BMI z-score (BMIz) change on CKD progression among participants of the Chronic Kidney Disease in Children study. Kaplan-Meier survival curves and multivariable parametric failure time models depict the association of baseline BMI category on time to kidney replacement therapy (KRT). Additionally, the annualized percentage change in estimated glomerular filtration rate (eGFR) was modeled against concurrent change in BMIz using multivariable linear regression with generalized estimating equations which allowed for quantification of the effect of BMIz change on annualized eGFR change. Participants had median age of 10.9years [IQR: 6.5, 14.6], median eGFR of 50ml/1.73 m2 [IQR: 37, 64] and 63% were male. 160 (27%) of 600 children with non-glomerular and 77 (31%) of 247 children with glomerular CKD progressed to KRT over a median of 5years [IQR: 2, 8]. Times to KRT were not significantly associated with baseline BMI category. Children with non-glomerular CKD who were obese experienced significant improvement in eGFR (+ 0.62%; 95% CI: + 0.17%, + 1.08%) for every 0.1 standard deviation concurrent decrease in BMI. In participants with glomerular CKD who were obese, BMIz change was not significantly associated with annualized eGFR change. Obesity may represent a target of intervention to improve kidney function in children with non-glomerular CKD. A higher resolution version of the Graphical abstract is available as Supplementary information.

Changes in BMI During the COVID-19 Pandemic.

Experts hypothesized increased weight gain in children associated with the coronavirus disease 2019 (COVID-19) pandemic. Our objective was to evaluate whether the rate of change of child body mass index (BMI) increased during the COVID-19 pandemic compared with prepandemic years. The study population of 1996 children ages 2 to 19 years with at least 1 BMI measure before and during the COVID-19 pandemic was drawn from 38 pediatric cohorts across the United States participating in the Environmental Influences on Child Health Outcomes-wide cohort study. We modeled change in BMI using linear mixed models, adjusting for age, sex, race, ethnicity, maternal education, income, baseline BMI category, and type of BMI measure. Data collection and analysis were approved by the local institutional review board of each institution or by the central Environmental Influences on Child Health Outcomes institutional review board. BMI increased during the COVID-19 pandemic compared with previous years (0.24 higher annual gain in BMI during the pandemic compared with previous years, 95% confidence interval 0.02 to 0.45). Children with BMI in the obese range compared with the healthy weight range were at higher risk for excess BMI gain during the pandemic, whereas children in higher-income households were at decreased risk of BMI gain. One effect of the COVID-19 pandemic is an increase in annual BMI gain during the COVID-19 pandemic compared with the 3 previous years among children in our national cohort. This increased risk among US children may worsen a critical threat to public health and health equity.

Impact of body mass index on pathological complete response and survival of breast cancer patients receiving neoadjuvant chemotherapy.

High body mass index (BMI) is regarded as a poor prognostic factor in breast cancer (BC). However, its association with pathological complete response (pCR) and survival after neoadjuvant chemotherapy (NAC) remains controversial. We wanted to assess the prognostic impact of BMI in this setting. Single-center, retrospective review of 314 BC patients undergoing NAC from 2010 to 2018. Patients were categorized as underweight/normal weight (UW/NW) (BMI < 25) or overweight/obese (OW/OB) (BMI ≥ 25). The relationship between BMI and other traditional clinical-pathological prognostic variables with the pCR rate was investigated using logistic regression analysis. The effect on event-free survival (EFS) and overall survival (OS) was estimated by the Cox proportional hazards regression analysis. One hundred and twenty-two patients were UW/NW while 192 were OW/OB. Multivariate analysis revealed that hormonal receptors negative, HER2 positive, and clinical tumor stage (cT) 1-2 were independent predictor factors for pCR. Multivariate analysis confirmed tumor grade G3 and lack of pCR as independent adverse prognostic factors for EFS, while factors associated with worse OS were cT3-4, hormone receptors negative, and lack of pCR. Non-significant differences in pCR, EFS, or OS were observed between the two baseline BMI categories. In our experience, BMI is not associated with pCR, EFS, or OS in BC patients receiving NAC. Achieving pCR is the most consistent factor associated with EFS and OS. Prospective and well-designed studies taking into account other important biological and anthropometric factors are needed to determine the exact role of BMI in this setting.

Efficacy and safety of relugolix in men with advanced prostate cancer based on baseline body mass index (BMI): A subgroup analysis from the randomized, phase 3 HERO study versus leuprolide (LEU).

5073 Background: BMI has been correlated with adverse prostate cancer outcomes, such as risk of biochemical failure, mortality and androgen deprivation therapy complications. Relugolix is a FDA-approved, once-daily oral GnRH receptor antagonist that has demonstrated superior continuous suppression of testosterone (T) to castrate levels through Week 48 compared to LEU (96.7% vs 88.8%, respectively; Shore N, NEJM 2020;382:2187) in men with advanced prostate cancer (APC). This HERO subgroup analysis looks at the impact of baseline BMI on efficacy and safety. Methods: HERO was a phase 3 randomized, open-label study to evaluate relugolix vs LEU in 930 men with APC. This analysis looked at all men enrolled and treated in the HERO study divided by baseline BMI (BMI subgroups: &lt;25.0 [underweight and healthy weight]; 25.0 – 29.9 [overweight]; and &gt;29.9 [obese]). Assessments included sustained T suppression to castrate levels (&lt;50 ng/dL) from Day 29 through 48 weeks, early T suppression to castrate levels (Day 4 and Day 15), prostate specific antigen (PSA) response (&gt;50% decrease from baseline) at Day 15 with confirmation at Day 29, and profound castration rate (&lt;20 ng/dL) at Day 15. T recovery subset analysis was not included due to low patient numbers. All analyses performed were descriptive. Results: Of the 930 men (relugolix:622; LEU:308) treated in HERO, 287 (30.9%) men had BMI &lt;25, 424 (45.6%) were 25 – 29.9, 219 (23.5%) were &gt;29.9. Sustained castration rates through 48 weeks were higher for the relugolix group than the LEU group and results for select key secondary endpoints were generally consistent across BMI categories, although PSA response proportions were lower in obese patients (table). No differences were noted in the incidence or types of adverse events within treatment groups in the subgroups analyzed. Conclusions: In this HERO study subgroup analysis, relugolix demonstrated greater continuous T suppression than LEU regardless of baseline BMI. Although higher BMI has been associated with poorer outcomes, we did not observe a similar trend with T responses. A numerically lower PSA response was seen in obese patients. Additional research with longer follow-up is warranted. Clinical trial information: NCT03085095. [Table: see text]

Comparison of Ambulatory Health Care Costs and Use Associated With Roux-en-Y Gastric Bypass vs Sleeve Gastrectomy

Studies comparing contemporary bariatric surgical types could facilitate procedure selection for patients interested in reducing their frequency of health care visits and reliance on prescription drugs. To compare the association of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) with ambulatory health care costs and use for as long as 4 years after surgery. This comparative effectiveness study, which included patients undergoing bariatric surgery who were aged 18 to 64 years with at least 24 months of enrollment data before surgery and 12 months of enrollment data after surgery, used a retrospective interrupted time series with a comparison group. Data represent insurance claims dated January 2006 to June 2017, with analyses completed in September 2021. Data were collected from US commercial and Medicare Advantage claims database. Cohorts were matched on characteristics including baseline body mass index category, diabetes status, baseline ambulatory care costs, region of the United States, and year of surgery. SG or RYGB, based on procedure codes. Annual ambulatory health care costs, and subtypes of cost and use including prescriptions, office visits, laboratory encounters, and radiology. Matched cohorts included 3049 patients who underwent SG and 3251 patients who underwent RYGB, with a mean (SD) age of 45.2 (10.0) years; 4820 (77%) were women. Full follow-up was 37% for SG (514 patients) and 38% for RYGB (643 patients) among those eligible for 4-year follow-up. There were no significant differences between SG and RYGB in total ambulatory costs, office visit costs, or radiology costs in all follow-up years. Patients who underwent SG had significantly higher prescription costs than those who underwent RYGB bypass in year 4 ($852.8 per patient per year; 95% CI: $395.6-$1310.0 per patient per year) with more cardiometabolic medication fills in each year (eg, year 4: 42.5%; 95% CI, 13.7%-71.2%). In contrast, early after surgery, patients who underwent SG had relatively fewer specialist visits (eg, year 1: -7.2%; 95% CI, -14.3% to -0.2%) and lower laboratory costs (eg, year 1: -$118.9 per patient per year; 95% CI, -$220.2 to -$17.5 per patient per year). Despite clinical studies showing greater weight loss and comorbidity improvement with RYGB vs SG, this study found no difference in total ambulatory costs for as long as 4 years after SG and RYGB. These findings may reflect the trade-off between greater improvements in cardiometabolic health and additional surgery-related care among patients undergoing RYGB. Studies with longer follow-up time could determine whether greater sustained weight loss from RYGB eventually results in lower costs compared with SG.

Changes in body mass index, weight, and height in children with acute myeloid leukemia and the associations with outcome

AbstractLittle is known about body composition changes in patients with acute myeloid leukemia (AML) during and after treatment or their associations with outcomes. Z-scores for body mass index (BMI), weight, and height at diagnosis, their longitudinal changes from diagnosis to 5 years off therapy, and their associations with adverse effects and outcomes were evaluated in 227 pediatric patients with AML enrolled in the AML02 and AML08 trials at St. Jude Children's Research Hospital between 2002-2017. The median Z-scores for baseline weight, height, and BMI were 0.193, 0.209, and 0.170, respectively, and those for weight and height decreased significantly during therapy to −0.038 and −0.163, respectively, at off-therapy (P < .001 for both). At 5 years off therapy, the Z-scores for weight and BMI had increased significantly to 0.492 (P = .003) and 0.911 (P < .001), respectively, whereas the height Z-score remained significantly lower at −0.066 (P < .001) compared with baseline. The height Z-score of transplant recipients decreased further from −0.211 at transplant to −0.617 12 months later (P < .001). Baseline BMI category and Z-score were not associated with outcomes, but higher weight Z-scores were associated with lower incidences of refractory or relapsed disease (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.67-0.99) and higher incidences of death in remission (HR, 1.31; 95% CI, 1.01-1.70). Furthermore, weight Z-score decrease during induction therapy was associated with gastrointestinal, hepatic, and infection toxicities during subsequent therapy and with death in remission (HR, 2.66; 95% CI, 1.11-6.45). Multidisciplinary monitoring for weight changes and short stature is required from diagnosis to the off-therapy period.

Association of weight status and the risks of diabetes in adults: a systematic review and meta-analysis of prospective cohort studies.

Obesity is a known risk factor for type 2 diabetes mellitus (T2DM); however, the associations between underweight and T2DM and between weight status and prediabetes have not been systematically reviewed. We aimed to estimate the relative risks (RRs) of prediabetes/T2DM in underweight/overweight/obesity relative to normal weight. PubMed, Embase, Web of Science, and Cochrane Library were searched from inception to December 8, 2021. Prospective cohort studies with a minimum 12-month follow-up period reporting the association between baseline body mass index (BMI) categories and risk of prediabetes/T2DM in adults were included. Study quality was assessed using the Newcastle-Ottawa Scale. The main analyses of T2DM risk were performed using the ethnic-specific (Asian/non-Asian) BMI classification and additional analyses of prediabetes/T2DM risk by including all eligible studies. Random-effects models with inverse variance weighting were used. Subgroup analyses and meta-regression were conducted to explore the potential effects of pre-specified modifiers. The study protocol was registered with PROSPERO (CRD42020215957). Eighty-four articles involving over 2.69 million participants from 20 countries were included. The pooled RR of prediabetes risk was 1.24 (95% CI: 1.19-1.28, I2 = 9.7%, n = 5 studies) for overweight/obesity vs. normal weight. The pooled RRs of T2DM based on the ethnic-specific BMI categories were 0.93 (95% CI: 0.75-1.15, I2 = 55.5%, n = 12) for underweight, 2.24 (95% CI: 1.95-2.56, I2 = 92.0%, n = 47) for overweight, 4.56 (95% CI: 3.69-5.64, I2 = 96%, n = 43) for obesity, and 22.97 (95% CI: 13.58-38.86, I2 = 92.1%, n = 6) for severe obesity vs. normal weight. Subgroup analyses indicated that underweight is a protective factor against T2DM in non-Asians (RR = 0.68, 95% CI: 0.40-0.99, I2 = 56.1%, n = 6). The magnitude of the RR of T2DM in overweight/obesity decreased with age and varied by region and the assessment methods for weight and T2DM. Overweight/obesity was associated with an increased prediabetes/T2DM risk. Further studies are required to confirm the association between underweight and prediabetes/T2DM, particularly in Asian populations.

Abstract P2-11-11: Impact of baseline body mass index (BMI) and weight changes after diagnosis in young women with early breast cancer (BC): A multicenter retrospective study

Abstract Background: Prior studies demonstrated that premenopausal obese women with BC have a poorer prognosis than non-obese patients (pts). We examined time trends in the prevalence of overweight and obesity among young women diagnosed with early BC and assessed the impact of baseline BMI and weight changes in disease outcomes. Patients and methods: Multicenter retrospective cohort study including young women (≤40yrs) diagnosed with stage I-III BC during 2000-2016 treated in two large Belgian hospitals. Data on baseline characteristics, treatment, and survival outcomes were collected. Pts were classified according to baseline BMI into underweight (&amp;lt;18.5 kg/m2), normal weight (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2) and obese (≥30 kg/m2). Landmark analysis at 2y after diagnosis (+/-6 months) was performed to evaluate the impact of weight changes (≥5% from baseline) on disease outcomes. Univariate hazard ratios were calculated for outcomes of interest (invasive disease-free survival [IDFS], distant recurrence-free interval [DRFI], overall survival [OS]). Multivariable analysis adjusting for factors that differed between groups was performed for the analysis of 2 BMI categories. Results: A total of 1,849 eligible pts were included, of whom 1,371 (74.1%) had a BMI recorded: 84 (6.1%) were underweight, 871 (63.5%) had normal weight, 304 (22.1%) were overweight and 112 (8.1%) were obese. Baseline BMI was similar across age groups. Overweight and obese pts had significantly larger tumor size when compared to underweight and normal weight pts (p=0.002) with similar rates of nodal involvement. The proportion of pts diagnosed with a BMI ≥25 significantly increased over time (OR: 1.03; 1.00-1.05 p=0.024). There was no difference in OS, DRFI and IDFS according to baseline BMI when grouping pts in the 4 BMI categories (underweight vs. normal weight vs. overweight vs. obese) or in the 2 BMI categories (underweight/normal weight vs. overweight/obese). Multivariate analysis with 2 BMI categories also did not demonstrate differences in OS, DRFI and IDFS. 1,023 pts had weight registered at 2y follow-up, of whom 360 (35.1%) were overweight, and 107 (10.4%) obese. Regarding weight changes, 117 (11.4%) presented weight loss, 617 (60.4%) stable weight, and 287 (28.1%) had weight gain. Weight gain was significantly associated with the use of endocrine therapy in general (p=0.029) and ovarian function suppression (p&amp;lt;0.001). In pts with baseline BMI ≥25, 59 (18.5%) lost weight, 185 (58%) maintained a stable weight, and 74 (23.2%) continued to gain weight. There was no statistically significant impact of weight changes at 2y on disease outcomes. Conclusions: Our time trend analysis suggests that the prevalence of overweight and obesity among young women with BC is increasing over time, highlighting the need for preventing overweight/obesity. In this retrospective analysis, BMI had no impact on disease outcomes. Prospective studies and analyzes of body composition can add important information in this regard. Weight gain after BC diagnosis was significantly associated with the use of endocrine therapy and ovarian function suppression and is a prevalent issue among young women, with 23% of overweight/obese pts at diagnosis continuing to gain weight. Further studies evaluating weight changes and interventions to prevent weight gain are needed to better inform survivorship programs. Table 1.- Impact of Baseline BMI and weight changes on disease outcomesOverall survival (OS)4 BMI categories (baseline)Hazard ratio2 BMI categories (baseline)Hazard ratioNormal weightReferenceUnderweight/normal weight (BMI&amp;lt;25)ReferenceUnderweight1.37 (0.8-2.2)Overweight1.01 (0.7-.1.3)Overweight/obese (BMI≥25)1.05 (0.7-1.3)Obese1.28 (0.4-1.2)Distant Recurrence-Free Interval (DRFI)Normal weightReferenceUnderweight/normal weight (BMI&amp;lt;25)ReferenceUnderweight0.86 (0.5-1.3)Overweight0.88 (0.6-1.1)Overweight/obese (BMI≥25)0.91 (0.7-1.1)Obese0.94 (0.6-1.3)Invasive disease-free survival (IDFS)Normal weightReferenceUnderweight/normal weight (BMI&amp;lt;25)ReferenceUnderweight0.88 (0.5-1.3)Overweight0.88 (0.6-1.1)Overweight/obese (BMI≥25)0.92 (0.7-1.1)Obese0.99 (0.6-1.4)Weight changes analysisWeight changes categoryHazard ratio for OSHazard ratio for DRFIHazard ratio for IDFSStable weightReferenceReferenceReferenceWeight Loss1.45 (0.9-2.2)1.11 (0.6-1.8)1.05 (0.6-1.6)Weight Gain0.77 (0.5-1.14)0.92 (0.6-1.3)0.92 (0.6-1.2) Citation Format: Maria Alice Franzoi, Kevin Punie, Annouschka Laenen, Boudewijn Dullens, Celia Fernandes Costa, Patrick Neven, Hans Wildiers, Matteo Lambertini, Evandro de Azambuja. Impact of baseline body mass index (BMI) and weight changes after diagnosis in young women with early breast cancer (BC): A multicenter retrospective study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-11-11.

Abstract PD5-11: Pilot study to assess prolonged nightly fasting in breast cancer survivors (LONGFAST)

Abstract Background: Prior, retrospective analysis of nightly fasting among women with breast cancer suggests that fasting less than 13 hours per night may be associated with higher risk of breast cancer recurrence. Small studies suggest that fasting duration can influence inflammation, obesity, sleep, and other potential mediators of breast cancer recurrence risk. Prolonged overnight fasting is a simple, nonpharmacological behavioral intervention strategy that may be doable for most patients. We designed this pilot study to prospectively evaluate the feasibility of prolonged overnight fasting among breast cancer survivors. Methods: We designed a single-arm, pilot study to evaluate the feasibility of fasting for 13 hours overnight for a 12-week period among women with a history of early stage breast cancer (I to III) who had completed initial cancer therapy at least 6 months prior. Baseline and end of study assessments included measurements of body mass index (BMI), quality of life (QOL) (Functional Assessment of Cancer Therapy - General (FACT-G)), mood (Hospital Anxiety and Depression Scale (HADS)), fatigue (Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue), levels of physical activity (Godin Leisure-Time Exercise Questionnaire), and blood biomarkers (expanded lipid profile, hemoglobin A1c, C-reactive protein, interleukin-6, tumor necrosis factor alpha, leptin, adiponectin). Patient-reported outcome (PRO) surveys were also administered at 6 weeks. Feasibility was defined as ≥ 60% of participants documenting fasting in the food diary for 13 hours on at least 70% of nights during the study period. Changes in study measures from baseline were evaluated using Wilcoxon signed-rank tests. Results: Between July 2020 and January 2021, we enrolled 40 women with a history of breast cancer. Participants had a median age of 59.9 (range 34.9-76.3) and median time since diagnosis was 4.5 years (range 0.8-20.7). At baseline, BMI was normal (18.5-24.9) in 40.0%, overweight (25-29.9) in 37.5%, and obese (≥30) in 22.5%. Forty-two and a half percent had Stage I cancer, 42.5% stage II, and 15.0% stage III. Sixty-five percent were on hormonal therapy. Ninety-five percent of participants fasted ≥ 13 hours for at least 70% of study days (95% CI 83%-99%). At 6 weeks, there was a statistically significant improvement in anxiety (p=.0007). No other significant changes were seen in PROs. At 12 weeks, there were statistically significant improvements in BMI (p=.0072), anxiety (p=.0141), depression (p=.0048), and fatigue (p=.0105). There was no association between change in BMI during the study and baseline BMI category, age, or endocrine therapy. There was no significant change in overall QOL, physical activity levels, or blood biomarkers at 12 weeks. Conclusions: Prolonged overnight fasting is feasible in the breast cancer population and may improve BMI, mood, and fatigue without a detrimental effect on overall QOL. The data from this study support the need for a larger, longer randomized study of prolonged overnight fasting in the breast cancer population to further evaluate the effects on body composition, mood, QOL, metabolic markers, and risk of recurrence. Table 1.Impact of Prolonged Overnight Fasting among Breast Cancer SurvivorsStudy AssessmentMedian at baselineMedian at 12 weeksMedian within-participant changep-valueBody Mass Index (kg/m2)26.4225.80-0.380.0072HADS - Depression1.001.00-1.000.0048HADS - Anxiety4.504.00-0.500.0141FACIT - Fatigue47.5049.821.000.0105FACT-G - Quality of Life95.2096.840.910.4933Physical Activity Level40.5039.000.000.3340Hemoglobin A1c (mg/dL)5.455.400.000.2758High-density lipoprotein (mg/dL)72.0073.00-2.000.4688Low-density lipoprotein (mg/dL)92.0099.001.000.5626Total Cholesterol (mg/dL)193.00192.003.000.6569C-reactive protein (mg/L)1.500.90-0.100.1043Interleukin-6 (pg/mL)2.001.90-0.300.1213Tumor Necrosis Factor α (pg/mL)0.740.74-0.050.2898Adiponectin (ug/mL)12.0012.000.000.0682Leptin (ng/mL)7.158.30-0.100.8418 Citation Format: Elizabeth K. O'Donnell, Yael N. Shapiro, Amy Comander, Steven J. Isakoff, Beverly Moy, Laura Spring, Seth Wander, Irene Kuter, Jennifer Shin, Jerry Younger, Michelle Specht, Chryssanthi Kourniotis, Carol Sullivan, Loren Winters, Nora Horick, Jeffrey Peppercorn. Pilot study to assess prolonged nightly fasting in breast cancer survivors (LONGFAST) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD5-11.

69. Incidence of metabolic complications among treatment-naïve adults living with HIV-1 randomized to B/F/TAF, DTG/ABC/3TC or DTG+F/TAF after 144 Weeks

BackgroundMetabolic comorbidities including diabetes (DM) and dyslipidemia pose challenges to the long-term care of people with HIV (PWH). Incidence of cardiovascular disease and DM are reported at higher rates in PWH than the general population. Obesity is broadly prevalent in both the general population and PWH, and higher body mass index (BMI) can contribute to metabolic complications. Here we present longer-term follow up on incidence of DM, hypertension (HTN), BMI categorical shifts, and lipid changes over 144 weeks of blinded treatment from two trials of PWH initiating antiretroviral therapy.MethodsWe assessed incidence of metabolic complications in adult PWH in Study 1489: bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) vs dolutegravir/abacavir/ lamivudine (DTG/ABC/3TC) and Study 1490: B/F/TAF vs DTG+F/TAF. Treatment-emergent (TE) metabolic comorbidities were defined by standard MedDRA search lists. CDC-defined BMI categories were compared from baseline (BL) to Week 144. Analyses by sex at birth and race were performed, as well as for lipid changes.ResultsAmong 1,274 total participants, median (range) age was 33 years (18-77), 90% men, 33% black. In study 1489, BL prevalence of DM and HTN was 4.5 and 12.1% with TE DM and HTN in B/F/TAF being 0.7% and 10%, and for DTG/ABC/3TC 1.3% and 6.9%, respectively. In study 1490, BL prevalence of DM and HTN was 6.8 and 18.8% with TE DM and HTN in B/F/TAF being 2.1 and 5.8%, and for DTG+F/TAF 2.3 and 6.5%, respectively. BMI shift from Normal to Obese: B/F/TAF 0%, DTG/ABC/3TC 3.2%, p=0.12 (1489) (Table 1); B/F/TAF 2.5%, DTG+F/TAF 2.9% p=1.00 (1490) (Table 2). Subgroup analyses by gender/race showed similar findings for TE DM, HTN, and BMI changes. Median changes from BL fasted lipids were small (Table 1).Table 1§. Studies 1489 and 1490: Metabolic Outcomes from Baseline to Week 144 Table 2±. Shift Table of BMI Category at Week 144 by Baseline BMI Category – Overall ConclusionThrough over 144 weeks of follow up, PWH randomized to initiate B/F/TAF, DTG/ABC/3TC or DTG+F/TAF had low rates of incident DM or HTN-related AEs, with no statistically significant differences by treatment group. BMI changes/categorical shifts from BL did not significantly differ by regimen, and no clinically significant change or difference by regimen in lipids were observed. While data are limited by three years of follow up, they are strengthened by randomized study design of three widely used initial ART regimens.Disclosures Eric Daar, MD, Bristol-Myers Squibb (Consultant)Gilead Sciences Inc. (Consultant, Scientific Research Study Investigator, Advisor or Review Panel member, Research Grant or Support)Janssen (Consultant, Advisor or Review Panel member, Research Grant or Support)Merck (Consultant, Advisor or Review Panel member, Research Grant or Support)Teva (Consultant, Advisor or Review Panel member)ViiV Healthcare (Consultant, Advisor or Review Panel member, Research Grant or Support) Chloe Orkin, MD, Gilead Sciences Inc. (Grant/Research Support, Scientific Research Study Investigator, Other Financial or Material Support)Janssen (Research Grant or Support, Other Financial or Material Support)Merck (Research Grant or Support, Other Financial or Material Support)ViiV Healthcare (Research Grant or Support, Other Financial or Material Support) Paul Sax, MD, Gilead Sciences (Consultant, Grant/Research Support)Janssen (Consultant)Merck (Consultant, Research Grant or Support)ViiV (Consultant, Research Grant or Support) Jeffrey L. Stephens, MD, Gilead Sciences Inc. (Scientific Research Study Investigator, Research Grant or Support) Ellen Koenig, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Amanda Clarke, MD, Gilead Sciences Inc. (Consultant, Scientific Research Study Investigator, Other Financial or Material Support, Conference attendance sponsorship)ViiV Healthcare (Consultant, Other Financial or Material Support, Conference travel sponsorship) Axel Baumgarten, MD, AbbVie (Advisor or Review Panel member, Speaker’s Bureau)Bristol-Myers Squibb (Advisor or Review Panel member, Speaker's Bureau)Gilead Sciences Inc. (Scientific Research Study Investigator, Advisor or Review Panel member, Speaker's Bureau)Janssen (Speaker’s Bureau)Merck (Advisor or Review Panel member) Cynthia Brinson, MD, Abbvie (Scientific Research Study Investigator)BI (Scientific Research Study Investigator)Gilead Sciences Inc. (Scientific Research Study Investigator, Advisor or Review Panel member, Speaker's Bureau, Personal fees)GSK (Scientific Research Study Investigator)Novo Nordisk (Scientific Research Study Investigator)ViiV Healthcare (Scientific Research Study Investigator, Advisor or Review Panel member, Speaker's Bureau) Moti Ramgopal, MD FIDSA, Abbvie (Scientific Research Study Investigator, Speaker's Bureau)Gilead (Consultant, Scientific Research Study Investigator, Speaker's Bureau)Janssen (Consultant, Scientific Research Study Investigator, Research Grant or Support, Speaker's Bureau)Merck (Consultant, Scientific Research Study Investigator)ViiV (Consultant, Scientific Research Study Investigator, Speaker's Bureau) Hailin Huang, PhD, Gilead Sciences Inc. (Employee, Shareholder) Terry Farrow, MD, Gilead Sciences Inc. (Employee, Shareholder) Jared Baeten, MD, PHD, Gilead Sciences Inc. (Employee, Shareholder) Jason Hindman, PharmD, Gilead Sciences Inc. (Employee, Shareholder) Hal Martin, MD, MPH, Gilead Sciences Inc. (Employee, Shareholder) Kimberly Workowski, MD, Nothing to disclose