Global patterns in excess body weight and the associated cancer burden.

The prevalence of excess body weight and the associated cancer burden have been rising over the past several decades globally. Between 1975 and 2016, the prevalence of excess body weight in adults-defined as a body mass index (BMI) ≥ 25 kg/m2 -increased from nearly 21% in men and 24% in women to approximately 40% in both sexes. Notably, the prevalence of obesity (BMI ≥ 30 kg/m2 ) quadrupled in men, from 3% to 12%, and more than doubled in women, from 7% to 16%. This change, combined with population growth, resulted in a more than 6-fold increase in the number of obese adults, from 100 to 671 million. The largest absolute increase in obesity occurred among men and boys in high-income Western countries and among women and girls in Central Asia, the Middle East, and North Africa. The simultaneous rise in excess body weight in almost all countries is thought to be driven largely by changes in the global food system, which promotes energy-dense, nutrient-poor foods, alongside reduced opportunities for physical activity. In 2012, excess body weight accounted for approximately 3.9% of all cancers (544,300 cases) with proportion varying from less than 1% in low-income countries to 7% or 8% in some high-income Western countries and in Middle Eastern and Northern African countries. The attributable burden by sex was higher for women (368,500 cases) than for men (175,800 cases). Given the pandemic proportion of excess body weight in high-income countries and the increasing prevalence in low- and middle-income countries, the global cancer burden attributable to this condition is likely to increase in the future. There is emerging consensus on opportunities for obesity control through the multisectoral coordinated implementation of core policy actions to promote an environment conducive to a healthy diet and active living. The rapid increase in both the prevalence of excess body weight and the associated cancer burden highlights the need for a rejuvenated focus on identifying, implementing, and evaluating interventions to prevent and control excess body weight.

Nutrition Assessment and Management in Celiac Disease.

Celiac disease (CeD) is the most common immune condition affecting the gastrointestinal tract; it is triggered by gluten and the only available treatment is a strict gluten-free diet (GFD). Therefore, for patients with CeD, adopting a GFD is not a lifestyle choice. The major problem is that a GFD is restrictive and, like all restrictive diets, it has the potential for adverse nutritional outcomes, especially if adopted for a long term. It is well known that GFD can be nutritionally inadequate and is frequently associated with vitamin and mineral deficiencies; it is also associated with excessive sugar and fat intake, particularly when gluten-free substitutes are consumed. Consequently, people with CeD are affected by higher rates of overweight and obesity and metabolic complications, such as fatty liver and cardiovascular disease. Therefore, assessment of nutritional status and diet quality at diagnosis and while on a long-term GFD is key in the management of CeD. This narrative review addresses nutritional considerations in CeD and management of common challenges associated with a GFD.

Birth Weight, Childhood and Young Adult Overweight, and the Risk of Coronary Heart Disease in Men.

BACKGROUND: Low birth weight is a known risk factor for adult coronary heart disease (CHD), but the additional effect of weight development during childhood and early adult life has not been studied. METHODS: We included 35 659 men born 1945 to 1961 from the population-based BMI Epidemiology Study Gothenburg, with data available on birthweight, BMI in childhood (8 years), and BMI in young adulthood (20 years). Information on CHD diagnoses was retrieved from national registers. We used Cox proportional hazards regression to estimate hazard ratios and 95% CIs for the risk of early and late CHD (before and after 58.4 years of age, respectively). RESULTS: During follow-up, a total of 3380 cases of CHD (fatal and nonfatal) were registered. Birth weight was inversely associated with the risk of both early (hazard ratio, 0.88 per SD increase [95% CI, 0.84-0.92]) and late (hazard ratio, 0.94 per SD increase [95% CI, 0.90-0.98]) CHD, independently of BMI at 8 years and BMI change during puberty. In a model including birth weight (below or above the median) together with overweight at 8 and 20 years, only birth weight and young adult overweight, but not overweight in childhood, were significantly associated with the risk of CHD. A birth weight below the median, followed by overweight at 20 years of age was associated with a more than doubled risk of early CHD (hazard ratio, 2.29 [95% CI, 1.86-2.81]), compared with the reference (birth weight above the median and normal weight at 20 years of age). This excess risk was even more pronounced for a birthweight below 2.5 kg. CONCLUSIONS: We demonstrate that low birth weight and young adult overweight are important developmental markers of risk for adult CHD. These findings motivate a life course perspective for prevention and risk assessment of adult CHD.

Obesity and immune-checkpoint inhibitors in advanced melanoma: A meta-analysis of survival outcomes from clinical studies.

Obesity is a chronic inflammatory condition that has been associated with different types of cancer. However, its role in melanoma incidence, progression, and response to immune-checkpoint-inhibitors (ICI) is still controversial. On the one hand, increased levels of lipids and adipokines can promote tumor proliferation and several genes associated with fatty acid metabolism have been found to be upregulated in melanomas. On the other hand, immunotherapy seems to be more effective in obese animal models, presumably due to an increase in CD8 + and subsequent decrease in PD-1 + T-cells in the tumor microenvironment. In humans, several studies have investigated the role of BMI (body mass index) and other adiposity-related parameters as potential prognostic markers of survival in advanced melanoma patients treated with ICI. The aim of this research has been to systematically review the scientific literature on studies evaluating the relationship between overweight/obesity and survival outcomes in patients with advanced melanoma treated with ICI and to perform a meta-analysis on those sharing common characteristics. After screening 1070 records identified through a literature search, 18 articles assessing the role of BMI-related exposure in relation to survival outcomes in ICI-treated patients with advanced melanoma were included in our review. In the meta-analysis of the association between overweight (defined as BMI>25 or BMI 25-30), overall survival (OS), and progression free survival (PFS), 7 studies were included, yielding a summary HR of 0.87 (95% CI: 0.74-1.03) and 0.96 (95% CI: 0.86-1.08), respectively. Our results show that, despite few suggestive findings, the use of BMI as a valuable predictor of melanoma patients' survival in terms of PFS and OS should not be currently recommended, due to the limited evidence available.

Low birthweight and overweight during childhood and young adulthood and the risk of type 2 diabetes in men: a population-based cohort study.

AIMS/HYPOTHESIS: This study aimed to determine the relative contributions of low birthweight and overweight during childhood and young adulthood to the risk of type 2 diabetes in men. METHODS: We included 34,231 men born between1945 and 1961 from the population-based BMI Epidemiology Study (BEST) Gothenburg with data on birthweight and overweight status in childhood (8 years, BMI >17.9 kg/m2) and young adulthood (20 years, BMI >25 kg/m2). Participants were followed from age 30 years until 31 December 2019. Information on type 2 diabetes diagnoses was retrieved from Swedish national registers. HRs and 95% CIs for the risk of early (≤59.4 years) and late (>59.4 years) type 2 diabetes were estimated using Cox proportional hazards regression. RESULTS: During follow-up, a total of 2733 cases of type 2 diabetes were diagnosed. Birthweight below the median (<3.6 kg) and overweight at age 20 (BMI >25 kg/m2), but not overweight at age 8 (BMI >17.9 kg/m2), were associated with an increased risk of early and late type 2 diabetes. Of note, a birthweight below the median followed by overweight at age 20 years was associated with a substantially increased risk of early type 2 diabetes (HR 6.07, 95% CI 5.08, 7.27), and a low birthweight (≤2.5 kg) combined with overweight at age 20 years was associated with a massive risk of early type 2 diabetes (HR 9.94, 95% CI 6.57, 15.05). CONCLUSIONS/INTERPRETATION: Low birthweight and overweight in young adulthood are the major developmental determinants of adult type 2 diabetes risk in men. They contribute in an additive manner to the risk of type 2 diabetes. To reduce the risk of type 2 diabetes, young adult overweight should be avoided, especially in boys with a low birthweight. DATA AVAILABILITY: The SPSS analysis code, the R analysis code and a data dictionary have been made available in an online repository ( https://osf.io/bx2as/ ).

Association between sex hormones and bone age in boys aged 9-18 years from China.

This study aimed to analyse the association between sex hormones and bone age (BA) in boys aged 9-18 years, both individually and interactively, and further to explore whether nutritional status may influence this association. A retrospective analysis was performed among 1382 Chinese boys with physical measurements, sexual characteristics, BA radiographs and sex hormone indicators from February 2015 to February 2022. A total of 470 (34.0%) boys had advanced BA. BA was positively associated with estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone in both advanced and normal BA groups after adjusting for age, genetic height and body mass index. Multiple logistic regression showed that after adjusting for covariates, estradiol (odds ratio [OR] = 1.66, 95% confidence interval [CI]: 1.14-2.12), LH (OR = 1.43, 95% CI: 1.04-1.96), and testosterone (OR = 1.58, 95% CI: 1.17-2.13) were significantly associated with the increased risk of advanced BA in boys, and the association was reinforced when these hormones were interactively explored. Stratified by nutritional status, the interaction between estradiol, LH, and testosterone showed a strong association with advanced BA in boys with normal weight.

Overweight in Adolescence and Young Adulthood in Association With Adult Cerebrovascular Disease: The NFBC1966 Study.

BACKGROUND: Risk factors for cerebrovascular disease in adulthood are well known. However, research on individuals' risk factors throughout their life span has been limited. This prospective cohort study aims to determine the effect of body mass index (BMI) and its changes in adolescence and young adulthood on early onset cerebrovascular disease. METHODS: This study includes 10 491 people (5185 women) from the Northern Finland Birth Cohort 1966. Height, weight, and BMI were measured at ages 14 and 31 years. Sex- and age-specific BMI ranges were used to define overweight and obesity. Data on ischemic and hemorrhagic cerebrovascular diseases between ages 14 and 54 years were extracted from national hospital and death registers. Cox proportion hazard models (95% CI) were used to estimate associations between BMI or its changes and cerebrovascular disease, while adjusting for sex, smoking, educational level, BMI at the other time point, and age at menarche for women. Additionally, sex-BMI interactions were calculated. RESULTS: A total of 452 individuals (4.7%) experienced cerebrovascular disease during the follow-up. The risk of ischemic cerebrovascular disease was increased for overweight women at ages 14 years (hazard ratio [HR], 2.49 [95% CI, 1.44-4.31]) and 31 years (HR, 2.13 [95% CI, 1.14-3.97]), as well as for obese women at ages 14 years (HR, 1.87 [95% CI, 0.76-4.58) and 31 years (HR, 2.67 [95% CI, 1.26-5.65]), with normal weight as the reference. These results were independent of earlier or later BMI. Similar associations were not found among men. The risk of hemorrhagic cerebrovascular disease was increased at age 31 years both among obese women (HR, 3.49 [95% CI, 1.13-10.7) and obese men (HR, 5.75 [95% CI, 1.43-23.1). The risk of any cerebrovascular disease related to overweight at age 14 years was 2.09× higher among girls than boys (95% CI, 1.06-4.15). The risk of ischemic cerebrovascular disease related to obesity at age 31 years was 6.96× higher among women than men (95% CI, 1.36-35.7). CONCLUSIONS: Among women, being overweight in adolescence or young adulthood increases the risk of cerebrovascular disease, especially ischemic, independent of their earlier or later BMI.

Overweight-years and cancer risk: A prospective study of the association and comparison of predictive performance with body mass index (Atherosclerosis Risk in Communities Study).

Excess body mass index (BMI) is associated with a higher risk of at least 13 cancers, but it is usually measured at a single time point. We tested whether the overweight-years metric, which incorporates exposure time to BMI ≥25 kg/m2 , is associated with cancer risk and compared this with a single BMI measure. We used adulthood BMI readings in the Atherosclerosis Risk in Communities (ARIC) study to derive the overweight-years metric. We calculated associations between the metric and BMI and the risk of cancers using Cox proportional hazards models. Models that either included the metric or BMI were compared using Harrell's C-statistic. We included 13,463 participants, with 3,876 first primary cancers over a mean of 19 years (SD 7) of cancer follow-up. Hazard ratios for obesity-related cancers per standard deviation overweight-years were 1.15 (95% CI: 1.05-1.25) in men and 1.14 (95% CI: 1.08-1.20) in women. The difference in the C-statistic between models that incorporated BMI, or the overweight-years metric was non-significant in men and women. Overweight-years was associated with the risk of obesity-related cancers but did not outperform a single BMI measure in association performance characteristics.

Environmental drivers of the rising incidence of early-onset colorectal cancer in the United States.

Incidence of early-onset (diagnosed before age 50) colorectal cancer (EOCRC) has increased alarmingly since the 1990s in the United States. This study investigated what environmental exposures may have driven this increase. We obtained EOCRC incidence data from the Surveillance, Epidemiology, and End Results Program, and data for 11 exposures, for example, body mass index (BMI), from long-term national surveys. We aggregated these data for 30 to 49-year-olds during 1992 to 2016 by population subgroups defined by calendar period, age, race and sex, and used negative binomial regression models to identify and estimate associations of EOCRC with multiple exposures. Furthermore, we used counterfactual modeling to quantify contributions of identified risk factors to EOCRC incidence. The top models (with lowest Bayesian Information Criteria) consistently identified excess body weight, represented by overweight and obesity (BMI ≥25) or obesity alone (BMI ≥30), as the strongest risk factor. The best-performing model estimated increased EOCRC incidence due to overweight and obesity, with an incidence rate ratio (95% confidence interval) of 1.20 (1.17-1.22) for white men, 1.04 (1.00-1.08) for black men, 1.17 (1.15-1.21) for white women and 1.03 (0.97-1.08) for black women. Increases in overweight and obesity prevalence contributed to an estimated 30% (standard error: 1%) for men and 28% (standard error: 2%) for women of ECORC incidence during 1992 to 2016. These findings suggest excess body weight substantially contributed to and is likely a primary driver of the rising incidence of EOCRC in the United States. Prevention of excess weight gain may help lower colorectal cancer risk early in life.

Safety, tolerability, pharmacokinetics, and pharmacodynamics of TG103 injection in participants who are overweight or obese: a randomized, double-blind, placebo-controlled, multiple-dose phase 1b study.

BACKGROUND: TG103, a glucagon-like peptide-1 analog, is being investigated as an option for weight management. We aimed to determine the safety, tolerability, pharmacokinetics, and pharmacodynamics of TG103 injection in participants who are overweight or obese without diabetes. METHODS: In this randomized, double-blind, placebo-controlled, multiple-dose phase 1b study, participants aged 18-75 years with a body-mass index (BMI) ≥ 26.0 kg/m2 and body weight ≥ 60 kg were enrolled from three centers in China. The study included three cohorts, and in each cohort, eligible participants were randomly assigned (3:1) to one of three once-weekly subcutaneous TG103 groups (15.0, 22.5 and 30.0 mg) or matched placebo, without lifestyle interventions. In each cohort, the doses of TG103 were escalated in 1-week intervals to the desired dose over 1 to 4 weeks. Then participants were treated at the target dose until week 12 and then followed up for 2 weeks. The primary endpoint was safety and tolerability assessed by the incidence and severity of adverse events (AEs) from baseline to the end of the follow-up period. Secondary endpoints included pharmacokinetic and pharmacodynamic profiles of TG103 and the occurrence of anti-drug antibodies to TG103. RESULTS: A total of 147 participants were screened, and 48 participants were randomly assigned to TG103 (15.0, 22.5 and 30.0 mg groups, n = 12 per group) or placebo (n = 12). The mean (standard deviation, SD) age of the participants was 33.9 (10.0) years; the mean bodyweight was 81.65 (10.50) kg, and the mean BMI was 29.8 (2.5) kg/m2. A total of 466 AEs occurred in 45 of the 48 participants, with 35 (97.2%) in the TG103 group and 10 (83.3%) in the pooled placebo group. Most AEs were grade 1 or 2 in severity, and there were no serious adverse events (SAEs), AEs leading to death, or AEs leading to discontinuation of treatment. The steady-state exposure of TG103 increased with increasing dose and was proportional to Cmax,ss, AUCss, AUC0-t and AUC0-inf. The mean values of Cmax,ss ranged from 951 to 1690 ng/mL, AUC0-t ranged from 150 to 321 µg*h/mL, and AUC0-inf ranged from 159 to 340 µg*h/mL. TG103 had a half-life of 110-116 h, with a median Tmax of 36-48 h. After treatment for 12 weeks, the mean (SD) values of weight loss from baseline in the TG103 15.0 mg, 22.5 mg and 30.0 mg groups were 5.65 (3.30) kg, 5.35 (3.39) kg and 5.13 (2.56) kg, respectively, and that in the placebo group was 1.37 (2.13) kg. The least square mean percent weight loss from baseline to D85 in all the TG103 groups was more than 5% with p < 0.05 for all comparisons with placebo. CONCLUSIONS: In this trial, all three doses of once-weekly TG103 were well tolerated with an acceptable safety profile. TG103 demonstrated preliminary 12-week body weight loss without lifestyle interventions, thus showing great potential for the treatment of overweight and obesity. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04855292. Registered on April 22, 2021.

Single-cell transcriptome analysis reveals immunosuppressive landscape in overweight and obese colorectal cancer.

BACKGROUND: Overweight and obesity are established risk factors for various types of cancers including colorectal cancer (CRC). However the underlying molecular mechanisms remain unclear. An in-depth understanding of the oncologic characteristics of overweight and obese CRC at the single-cell level can provide valuable insights for the development of more effective treatment strategies for CRC. METHODS: We conducted single-cell RNA sequencing (scRNA-seq) analysis on tumor and adjacent normal colorectal samples from 15 overweight/obese and 15 normal-weight CRC patients. Immunological and metabolic differences between overweight/obese CRC and non-obese CRC were characterized. RESULTS: We obtained single-cell transcriptomics data from a total of 192,785 cells across all samples. By evaluating marker gene expression patterns, we annotated nine main cell types in the CRC ecosystem. Specifically, we found that the cytotoxic function of effector T cells and NK cells was impaired in overweight/obese CRC compared with non-obese CRC, relating to its metabolic dysregulation. CD4+T cells in overweight/obese CRC exhibited higher expression of immune checkpoint molecules. The antigen-presenting ability of DCs and B cells is down-regulated in overweight/obese CRC, which may further aggravate the immunosuppression of overweight/obese CRC. Additionally, dysfunctional stromal cells were identified, potentially promoting invasion and metastasis in overweight/obese CRC. Furthermore, we discovered the up-regulated metabolism of glycolysis and lipids of tumor cells in overweight/obese CRC, which may impact the metabolism and function of immune cells. We also identified inhibitory interactions between tumor cells and T cells in overweight/obese CRC. CONCLUSIONS: The study demonstrated that overweight/obese CRC has a more immunosuppressive microenvironment and distinct metabolic reprogramming characterized by increased of glycolysis and lipid metabolism. These findings may have implications for the development of novel therapeutic strategies for overweight/obese CRC patients.

Dietary sulfur amino acid restriction in humans with overweight and obesity: a translational randomized controlled trial.

BACKGROUND: Dietary sulfur amino acid restriction (SAAR) improves metabolic health in animals. In this study, we investigated the effect of dietary SAAR on body weight, body composition, resting metabolic rate, gene expression profiles in white adipose tissue (WAT), and an extensive blood biomarker profile in humans with overweight or obesity. METHODS: N = 59 participants with overweight or obesity (73% women) were randomized stratified by sex to an 8-week plant-based dietary intervention low (~ 2 g/day, SAAR) or high (~ 5.6 g/day, control group) in sulfur amino acids. The diets were provided in full to the participants, and both investigators and participants were blinded to the intervention. Outcome analyses were performed using linear mixed model regression adjusted for baseline values of the outcome and sex. RESULTS: SAAR led to a ~ 20% greater weight loss compared to controls (ß 95% CI - 1.14 (- 2.04, - 0.25) kg, p = 0.013). Despite greater weight loss, resting metabolic rate remained similar between groups. Furthermore, SAAR decreased serum leptin, and increased ketone bodies compared to controls. In WAT, 20 genes were upregulated whereas 24 genes were downregulated (FDR < 5%) in the SAAR group compared to controls. Generally applicable gene set enrichment analyses revealed that processes associated with ribosomes were upregulated, whereas processes related to structural components were downregulated. CONCLUSION: Our study shows that SAAR leads to greater weight loss, decreased leptin and increased ketone bodies compared to controls. Further research on SAAR is needed to investigate the therapeutic potential for metabolic conditions in humans. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04701346, registered Jan 8th 2021, https://www. CLINICALTRIALS: gov/study/NCT04701346.

The coexistence of diabetes, hypertension and obesity is associated with worse pain outcomes following exercise for osteoarthritis: A cohort study on 80,893 patients.

OBJECTIVES: To investigate how the co-occurrence of diabetes, hypertension and overweight/obesity is associated with pain following an exercise intervention for knee and hip osteoarthritis (OA). METHODS: Register-based cohort study. We included people from the Swedish Osteoarthritis Register who underwent education and exercise for knee or hip OA. Diabetes and hypertension were defined using medical records and dispensation of medication. Body Mass Index (BMI) was used to identify people with overweight (≥25 to <30), and obesity (≥30). We used linear mixed-effect models with patients nested into clinics to estimate the associations between the exposures and pain (Numeric Rating Scale 0-10), adjusting for age, sex, education, and physical activity. RESULTS: We analysed 80,893 patients with knee or hip OA. The accumulation of metabolic conditions was associated with worse pain at baseline and follow-ups. When obesity, hypertension and diabetes coexisted, patients treated for knee OA reported more pain at baseline (adjusted mean pain difference 0.9 [95 %CI: 0.8; 1.0]), 3 months (1.0 [0.9; 1.1]) and 12 months (1.3 [1.1; 1.4]) compared to those without any of the conditions. Similar results were observed for patients treated for hip OA when obesity, hypertension and diabetes coexisted (baseline (0.7 [0.5; 0.8], 3 (0.8[0.6; 1.0]) and 12 months (1.1[0.8; 1.3]). CONCLUSIONS: When diabetes, hypertension and obesity coexist with OA, patients not only experience heightened baseline pain compared to metabolically healthy individuals, but the disparity increases after an education and exercise intervention suggesting that a one-size-fits-all approach may be inadequate in addressing the complex interplay between metabolic health and OA.

Peak serum luteinising hormone cut-off during gonadotropin-releasing hormone analogue test for diagnosing central precocious puberty was lower in girls with obesity as compared with girls with normal weight.

OBJECTIVE: Serum luteinising hormone (LH) concentration has been reported to be lower in girls with overweight and obesity (OW/OB) as compared with girls with normal weight (NW). This study aimed to evaluate peak serum LH concentration during gonadotropin-releasing hormone analogue (GnRHa) test in girls with OW/OB and NW who had central precocious puberty (CPP) and to determine peak serum LH cut-off for diagnosing CPP in girls with OW/OB. DESIGN, PATIENTS AND MEASUREMENTS: Medical records of 971 girls with premature breast development who underwent subcutaneous GnRHa (100 µg of triptorelin acetate) test were reviewed. All girls were classified as either CPP or premature thelarche. All of them were further classified into two groups according to their body mass index as NW and OW/OB groups for each Tanner stage. RESULTS: There were 634 and 337 girls in NW and OW/OB groups, respectively. CPP was diagnosed in 600 girls (249 had Tanner stage II and 351 had Tanner stage III). There were no differences in peak serum LH concentrations between CPP girls with NW and OW/OB. Peak serum LH cut-off of 5 IU/L (the current widely used cut-off) had a sensitivity and a specificity of 75% and 90%, respectively in NW group. Peak serum LH cut-off for CPP diagnosis was lower at 4 IU/L in the OW/OB group with greater sensitivity and specificity of 86% and 93%, respectively. The results were reproducible for each Tanner stage of breasts. CONCLUSION: Lower peak serum LH cut-off to 4 IU/L for diagnosing CPP in girls with OW/OB should be considered to avoid underdiagnosis of the condition.

Mild obesity does not affect perinatal outcome in gestational carrier cycles.

STUDY QUESTION: Does BMI of gestational carriers (GCs) affect perinatal outcomes after embryo transfer? SUMMARY ANSWER: Overweight and class I obesity in GCs does not affect the rate of good perinatal outcomes. WHAT IS KNOWN ALREADY: The use of GCs is increasing, but uniform guidance regarding optimal BMI for GCs is lacking. Women with obesity who conceive without fertility treatment or through autologous or donor in vitro fertilization are at higher risk of adverse maternal and fetal outcomes, but data on obesity in GCs are very limited. STUDY DESIGN, SIZE, DURATION: We performed a retrospective cohort study of 1121 GC cycles from January 2015 to December 2020 at US Fertility, the largest national partnership of fertility practices in the USA. PARTICIPANTS/MATERIALS, SETTING, AND METHODS: All GC cycles performed at a large network of fertility practices were reviewed. Same-sex partners undergoing co-IVF were excluded. The primary outcome was good perinatal outcome from the first embryo transfer, defined as a singleton live birth at ≥37 weeks of gestation with birth weight between 2500 and 4000 g. Secondary outcome measures included frequencies of live birth, clinical pregnancy, miscarriage, full-term birth, low birth weight, large for gestational age, and cesarean delivery. A generalized linear model (log-binomial) was used for each to compare outcomes across BMI groups using normal BMI (20-24.9 kg/m2) as the reference group. Risk ratios and 95% CIs were estimated for each category group relative to normal BMI. MAIN RESULTS AND THE ROLE OF CHANCE: We identified 1121 cycles in which GCs underwent first embryo transfer, of which 263 (23.5%) were in GCs with BMI >30. Demographics and reproductive history for GCs did not differ by BMI groups. The age of intended parents, use of frozen eggs, and fresh embryo transfers were higher with increasing BMI group. There were no statistically significant associations between BMI and good perinatal outcomes, live birth, clinical pregnancy, biochemical, spontaneous abortion, or low birth weight. However, among live births, higher BMI was significantly associated with birth by cesarean (P = 0.015) and large for gestational age infants (P = 0.023). LIMITATIONS, REASONS FOR CAUTION: This was a retrospective study, and there may be unmeasured confounders. The number of patients with BMI <20 or ≥35 was small, limiting the power for these groups. We were not able to assess all maternal and fetal outcomes. WIDER IMPLICATIONS OF THE FINDINGS: In this study, we did not identify any significant impact of BMI on the chances of having a good perinatal outcome. Prior research studies have been inconsistent and this is the largest study to date. STUDY FUNDING/COMPETING INTEREST(S): No external funding was received for this work. The authors do not have any conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Maternal pre-pregnancy BMI and reproductive health in adult sons: a study in the Danish National Birth Cohort.

STUDY QUESTION: Is maternal pre-pregnancy BMI associated with semen quality, testes volume, and reproductive hormone levels in sons? SUMMARY ANSWER: Maternal pre-pregnancy BMI was associated with an altered reproductive hormone profile in young adult sons, characterized by higher levels of oestradiol, LH, and free androgen index (FAI) and lower levels of sex hormone-binding globulin (SHBG) in sons born of mothers with pre-pregnancy overweight and obesity. WHAT IS KNOWN ALREADY: Evidence suggests that maternal pre-pregnancy BMI may influence reproductive health later in life. Only one pilot study has investigated the association between maternal pre-pregnancy BMI and reproductive health outcomes in sons, suggesting that a high BMI was associated with impaired reproductive function in the adult sons. STUDY DESIGN, SIZE, DURATION: A population-based follow-up study of 1058 young men from the Fetal Programming of Semen Quality (FEPOS) cohort nested within the Danish National Birth Cohort (DNBC), 1998-2019, was carried out. PARTICIPANTS/MATERIALS, SETTING, METHODS: In total, 1058 adult sons (median age 19 years, 2 months), born 1998-2000 by mothers included in the DNBC, participated in FEPOS. At a clinical examination, they provided a semen and blood sample, measured their testes volume, and had height and weight measured. Maternal pre-pregnancy BMI was obtained by self-report in early pregnancy. Semen characteristics, testes volume, and reproductive hormone levels were analysed according to maternal pre-pregnancy BMI categories and as restricted cubic splines using negative binomial and ordinary least square regression models. Mediation analyses examined potential mediation by the sons' birthweight, pubertal timing, fat mass, and BMI. Additional analyses investigated the role of paternal BMI in the potential associations between maternal BMI and reproductive health outcomes. MAIN RESULTS AND THE ROLE OF CHANCE: We found no consistent associations between maternal pre-pregnancy BMI and semen characteristics or testes volume. Sons of mothers with higher pre-pregnancy BMI had higher oestradiol and lower SHBG levels, both in a dose-dependent manner. Sons of mothers with pre-pregnancy obesity (≥30 kg/m2) had higher LH levels and a higher FAI than sons born by mothers with normal pre-pregnancy BMI (18.5-24.9 kg/m2). The mediation analyses suggested that the effect of maternal pre-pregnancy BMI on higher levels of oestrogen, LH, and FAI was partly mediated by the sons' birthweight, in addition to adult fat mass and BMI measured at the clinical examination, whereas most of the effect on lower levels of SHBG was primarily mediated by the sons' own fat mass and BMI. Paternal BMI was not a strong confounder of the associations in this study. LIMITATIONS, REASONS FOR CAUTION: This study was based in a population-based cohort with a low prevalence of overweight and obesity in both mothers and adult sons. Some men (10%) had blood for reproductive hormone assessment drawn in the evening. While several potential confounding factors were accounted for, this study's inherent risk of residual and unmeasured confounding precludes provision of causal estimates. Therefore, caution should be given when interpreting the causal effect of maternal BMI on sons' reproductive health. WIDER IMPLICATIONS OF THE FINDINGS: Given the widespread occurrence of overweight and obesity among pregnant women, it is imperative to thoroughly examine the potential consequences for reproductive hormone levels in adult sons. The potential effects of maternal pre-pregnancy obesity on sons' reproductive hormone profile may potentially be partly avoided by the prevention of overweight and obesity in the sons. STUDY FUNDING/COMPETING INTEREST(S): The project was funded by the Lundbeck Foundation (R170-2014-855), the Capital Region of Denmark, Medical doctor Sofus Carl Emil Friis and spouse Olga Doris Friis's Grant, Axel Muusfeldt's Foundation (2016-491), AP Møller Foundation (16-37), the Health Foundation, Dagmar Marshall's Fond, Aarhus University, Independent Research Fund Denmark (9039-00128B), and the European Union (ERC, BIOSFER, 101071773). Views and opinions expressed are, however, those of the authors only and do not necessarily reflect those of the European Union or the European Research Council. Neither the European Union nor the granting authority can be held responsible. The authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Long-term efficacy of washed microbiota transplantation in overweight patients.

BACKGROUND: Faecal microbiota transplantation holds promise in mitigating fat accumulation and improving obesity. This study aimed to evaluate the long-term efficacy of washed microbiota transplantation (WMT) among overweight patients. METHODS: The clinical data pertaining to the treatment of patients with WMT were collected retrospectively. Compared alterations in body mass index (BMI), blood glucose, blood lipids and blood pressure prior to and following WMT treatment. Comprehensive efficacy evaluation and atherosclerosis cardiovascular disease (ASCVD) grading evaluation were carried out, with an analysis of gut microbiota composition before and after WMT. RESULTS: A total of 186 patients were included (80 overweight, 106 normal weight). WMT not only had the effect of improving overweight patients to the normal weight patients (p < .001), but also could significantly reduce BMI in the long term by restoring gut microbiota homeostasis (p < .001). In addition, the BMI improvement value of multi course was more significant than that of single course or double course. WMT had a significant ASCVD downgrade effect on the high-risk and medium-risk groups outside 1 year, while it did not increase the risk of upgrading ASCVD for low-risk group. CONCLUSIONS: WMT could significantly reduce the BMI of overweight patients and still had an improvement effect in the long term.

Maternal overweight and obesity modify the association of serum fibroblast growth factor 21 levels with gestational diabetes mellitus: A nested case-control study.

AIMS: To examine the prospective association between fibroblast growth factor 21 (FGF21) and risk of gestational diabetes mellitus (GDM) and the modifying effect of overweight/obesity for this association. METHODS: Serum FGF21 levels were measured at 6-15 weeks of gestation among 332 GDM cases and 664 matched controls. Conditional logistic regression was used to evaluate its association with GDM risk. Interaction analyses on multiplicative and additive scales were conducted to investigate the modifying effect of overweight/obesity. RESULTS: Elevated FGF21 levels were associated with a higher risk of GDM in multivariable models, but the positive association was attenuated after further adjustment for pre-pregnancy body mass index (BMI). A significant multiplicative interaction was noted between FGF21 (both continuous and dichotomous) and pre-pregnancy BMI (p for interaction = 0.049 and 0.03), and the association was only significant in participants with pre-pregnancy BMI ≥24 kg/m2 . When participants were grouped based on pre-pregnancy BMI (≥24 and <24 kg/m2 ) and FGF21 levels (≥median and

Effects of Breastfeeding Promotion Intervention and Dietary Treatment in Postpartum Women with Overweight and Obesity: Results from a Randomized Controlled Trial on Weight and Cardiometabolic Risk Factors.

BACKGROUND: Childbearing increases the risk of weight gain and cardiometabolic disease. The reset hypothesis suggests that lactation has protective cardiometabolic effects on the mother. The hypothesis is based on observational studies, and the possible interacting role of weight loss needs to be elucidated. OBJECTIVES: This study aimed to examine the individual and interaction effects of a breastfeeding promotion intervention (BPI) and dietary intervention for weight loss postpartum (Diet) on body weight and cardiometabolic risk factors at 6 mo postpartum. METHODS: Pregnant women (n = 156) with a prepregnancy BMI of 25 to 35 kg/m2 were randomized to 4 groups in a 2 × 2 factorial design: BPI, Diet, both treatments, or no treatment. BPI consisted of individual counseling by a lactation consultant during pregnancy, at childbirth, and monthly thereafter or more frequently based on individual needs. Diet was initiated at 11 wk postpartum. Body weight, body composition, waist and hip circumferences, markers of lipid and glucose metabolism, and blood pressure were measured at 2 wk and 6 mo postpartum. We analyzed main and interaction effects using 2-way analysis of covariance adjusted for baseline values. RESULTS: Among the participants attending both visits (n = 108), 99% practiced any breastfeeding at baseline and 97% at follow-up. The BPI did not affect rates of exclusive or partial breastfeeding, age at introduction of complementary foods, or have main effects on body weight or cardiometabolic risk factors. There was a main effect of Diet reducing body weight, fat mass, fat-free mass, percentage fat mass, waist and hip circumferences, fasting glucose, and insulin (all P ≤ 0.03), with no interactions between the treatments. CONCLUSIONS: There were no effects of BPI on body weight or cardiometabolic risk factors at 6 mo postpartum. Diet caused weight loss and had favorable effects on risk factors for cardiovascular disease and type 2 diabetes. This study was registered at clinicaltrials.gov as NCT03580057.

Early life stress in relation with risk of overweight, depression, and their comorbidity across adulthood: findings from a British birth cohort.

BACKGROUND: Multimorbidity, known as the co-occurrence of at least two chronic conditions, has become of increasing concern in the current context of ageing populations, though it affects all ages. Early life risk factors of multimorbidity include adverse childhood experiences (ACEs), particularly associated with psychological conditions and weight problems. Few studies have considered related mechanisms and focus on old age participants. We are interested in estimating, from young adulthood, the risk of overweight-depression comorbidity related to ACEs while adjusting for early life confounders and intermediate variables. METHODS: We used data from the 1958 National Child Development Study, a prospective birth cohort study (N = 18 558). A four-category outcome (no condition, overweight only, depression only and, overweight-depression comorbidity) was constructed at 23, 33, and 42 years. Multinomial logistic regression models adjusting for intermediate variables co-occurring with this outcome were created. ACEs and sex interaction on comorbidity risk was tested. RESULTS: In our study sample (N = 7762), we found that ACEs were associated with overweight-depression comorbidity risk throughout adulthood (RRR [95% CI] at 23y = 3.80 [2.10-6.88]) though less overtime. Comorbidity risk was larger than risk of separate conditions. Intermediate variables explained part of the association. After full-adjustment, an association remained (RRR [95% CI] at 23y = 2.00 [1.08-3.72]). Comorbidity risk related to ACEs differed by sex at 42. CONCLUSION: Our study provides evidence on the link and potential mechanisms between ACEs and the co-occurrence of mental and physical diseases throughout the life-course. We suggest addressing ACEs in intervention strategies and public policies to go beyond single disease prevention.