Persistent Obesity Research Articles

The Efficacy and Safety of Liraglutide in Patients Remaining Obese 6 Months after Metabolic Surgery.

The safety and efficacy of liraglutide as a weight loss intervention in individuals who remain obese within 1year post-metabolic surgery remain unclear. This study aimed to evaluate the effects and safety of liraglutide (1.8mg) in patients with persistent obesity at 6months postoperatively. This retrospective cohort study included 61 patients who remained obese (body mass index [BMI] ≥ 28.0kg/m2) at 6months postoperatively. Among these patients, 27 were treated with 1.8mg of liraglutide for 12weeks, whereas 34 served as controls. The primary endpoint was the change in total weight loss (%TWL) after 24weeks. Changes in weight, BMI, complications, and adverse events were also assessed. The liraglutide group showed a greater reduction in %TWL than the control group (11.6% ± 1.1% vs. 4.9% ± 1.0%), with an estimated treatment difference of 6.6% (95% confidence interval [CI], 3.7-9.6%, P < 0.01). The adjusted mean differences in the reduction of weight and BMI between the liraglutide and control groups were -6.2kg (95% CI -8.9 to -3.4, P < 0.01) and -3.0kg/m2 (95% CI -4.2 to -1.7, P < 0.01), respectively. The liraglutide group exhibited increased rates of remission in non-alcoholic fatty liver disease and hypertension. No serious adverse reactions were observed. For patients who remained obese at 6months postoperatively, 12-week liraglutide treatment resulted in increased weight loss, improved metabolic control, and high rate of remission for obesity-related metabolic diseases after 24weeks. Earlier and more timely adjuvant weight loss medication intervention based on BMI within 1year postoperatively may enhance weight loss after metabolic surgery. Graphical abstract available for this article.

Assessment and medical management of weight regain after adolescent metabolic and bariatric surgery: a narrative review

BackgroundMetabolic and bariatric surgery (MBS) in adolescents results in durable treatment of severe obesity and related complications for most. However, substantial weight regain can undermine long-term health benefits. There is no evidence-based standard of care for the medical management of weight regain after MBS in pediatrics or adults. ObjectivesThis narrative review summarizes current pediatric evidence pertaining to the assessment and medical management of post-MBS weight regain, identify gaps, and offer recommendations. MethodsA PubMed search was conducted through March 2024 and focused on adolescents after sleeve gastrectomy or Roux-en-Y gastric bypass. Domains included nutrition, activity, mental health, anti-obesity medications (AOMs), type 2 diabetes, hypothalamic obesity, and transition of care. In total, 600 articles were screened and 61 were included in this review. ResultsRecent consensus definitions for post-MBS weight regain have been established for adults, but have not been validated in pediatrics. Limited, high-quality evidence was identified in the nutrition domain, where targets that may mitigate weight regain include adequate protein intake (>=60g/day), absence of loss of control eating, and micronutrient sufficiency. Emerging data for post-MBS AOMs in adults with/without diabetes and in adolescents with persistent obesity is promising. Large gaps include post-MBS interventions focused on physical activity and mental health. ConclusionsThe overall quality of pediatric-specific evidence for the assessment and medical management of post-MBS weight regain is low. A standard definition of weight regain associated with health outcomes in pediatrics would be valuable. Clarifying risk and protective factors for weight regain can guide more precise risk stratification and treatment.

Epidemiology of overweight in under-five children in India: insights from National Family Health Survey.

Childhood overweight is not only an immediate health concern due to its implications but also significantly increases the risk of persistent obesity and consequently CVD in the future, posing a serious threat to public health. The objective of this study was to examine the trends and associated factors of childhood overweight in India, using nationally representative data from three rounds of the National Family Health Survey (NFHS). For the primary analysis, we used data from 199375 children aged 0-59 months from fifth round of the NFHS (NFHS-5). Overweight was defined as BMI-for-age Z (BMI Z) score > +2 sd above the WHO growth standards median. We compared the prevalence estimates of childhood overweight with third round of the third round of NFHS and fourth round of the NFHS. Potential risk factors were identified through multiple logistic regression analyses. The prevalence of overweight increased from 1·9 % in third round of NFHS to 4·0 % in NFHS-5, a trend seen across most states and union territories, with the Northeast region showing the highest prevalence. The BMI Z-score distributions from the latest two surveys indicated that the increase in overweight was substantially larger than the decrease in underweight. The consistent upward trend in the prevalence across different demographic groups raises important public health concerns. While undernutrition rates have remained relatively stable, there has been a noticeable rise in the incidence of overweight during the same time frame. The increasing trend of overweight among children in India calls for immediate action.

Hypothalamic obesity: Epidemiology in rare sellar/suprasellar tumors-A German claims database analysis.

Hypothalamic obesity (HO) is defined as abnormal weight gain resulting in severe persistent obesity due to physical, tumor- and/or treatment-related damage to the hypothalamus. HO epidemiology is poorly understood. We developed a database algorithm supporting the standardized identification of tumor/treatment-related HO (TTR-HO) patients. The algorithm is used to estimate incidence rates of TTR-HO patients in the German healthcare context from a representative claims database (n = 5.42 million) covering 2010-2020. Patients were identified based on surgery/radiotherapy procedures and HO-associated tumor diagnoses (n = 3976). HO was defined by incident obesity and validated based on incident diabetes insipidus diagnoses and desmopressin prescription within a 12-month period after surgery/radiotherapy. Uncertainty due to algorithm definitions is explored in sensitivity analyses. Estimated annual incidence of TTR-HO in Germany is between 0.7 and 1.7 cases per 1,000,000 persons (2019 prevalence: n = 1262 patients). With observed cases in all age groups, two HO-incidence peaks are identified: children/young adults aged 10-24 years and adults aged 40-44 years. Most frequent HO-validated tumor diagnoses are benign sellar/suprasellar tumors (6.1/1,000,000 persons over 9 years), including tumors of the craniopharyngeal duct (1.3/1,000,000), neoplasms of the pituitary gland (4.1/1,000,000), and nonspecific brain tumors of endocrine glands (2.4/1,000,000). This is the first real-world database analysis of TTR-HO epidemiology, refining current estimates of HO epidemiology and early patient identification. A more comprehensive characterization of patients with HO as well as a better understanding of clinical implications will be crucial in developing optimal treatment strategies to improve patient outcomes.

Altered gait patterns during arch important development period in children with persistent obesity: An experimental longitudinal study

BackgroundObesity can cause structural changes and functional adjustments in growing children’s feet. However, there is a lack of continuous observation of changes in feet in children with persistent obesity during important developmental periods. This makes it challenging to provide precise preventive measures. ObjectiveThis study aimed to investigate the effects of persistent obesity on gait patterns in children at an important stage in the formation of a robust foot arch. MethodsThe Footscan® plantar pressure system was used for 3 checks over two years. A total of 372 children aged 7–8 years participated in the study, and gait data from 33 children who maintained normal weight and 26 children with persistent obesity were finally selected. Repeated measures ANOVA or Friedman’s test were used for longitudinal comparisons. Independent-Sample t-tests or the Mann-Whitney-Wilcoxon tests were used for cross-sectional comparisons. ResultsDuring the important period of development, children with persistent obesity did not exhibit a significant decrease in the arch index and had significantly higher values than the normal group in the third check. The persistently obese children showed increased load accumulation in the lateral rearfoot, first metatarsophalangeal joints, and the great toe regions. Children with persistent obesity had significantly greater medial-lateral displacements in the initial contact phase and forefoot contact phase than normal children in the first check. These differences diminished between the second and third checks. SignificancePersistent obesity during an important period of foot development leads to slow or abnormal development of arch structure and affects foot loading patterns with heel inverted and forefoot everted. Additionally, the development of gait stability is not limited by persistent obesity.

MicroRNAs as Epigenetic Regulators of Obesity.

In obesity, the process of adipogenesis largely determines the number of adipocytes in body fat depots. Adipogenesis is regulated by several adipocyte-selective micro-ribonucleic acids (miRNAs) and transcription factors that modulate adipocyte proliferation and differentiation. However, some miRNAs block the expression of master regulators of adipogenesis. Since the specific miRNAs display different expressions during adipogenesis, in mature adipocytes and permanent obesity, their use as biomarkers or therapeutic targets is feasible. Upregulated miRNAs in persistent obesity are downregulated during adipogenesis. Moreover, some of the downregulated miRNAs in obese individuals are upregulated in mature adipocytes. Induction of adipocyte stress and hypertrophy leads to the release of adipocyte-derived exosomes (AdEXs) that contain the cargo molecules, miRNAs. miRNAs are important messengers for intercellular communication involved in metabolic responses and have very specific signatures that direct the metabolic activity of target cells. While each miRNA targets multiple messenger RNAs (mRNAs), which may coordinate or antagonize each other's functions, several miRNAs are dysregulated in other tissues during obesity-related comorbidities. Deletion of the miRNA-processing enzyme DICER in pro-opiomelanocortin-expressing cells results in obesity, which is characterized by hyperphagia, increased adiposity, hyperleptinemia, defective glucose metabolism, and alterations in the pituitary-adrenal axis. In recent years, RNA-based therapeutical approaches have entered clinical trials as novel therapies against overweight and its complications. Development of lipid droplets, macrophage accumulation, macrophage polarization, tumor necrosis factor receptor-associated factor 6 activity, lipolysis, lipotoxicity, and insulin resistance are effectively controlled by miRNAs. Thereby, miRNAs as epigenetic regulators are used to determine the new gene transcripts and therapeutic targets.

Comparing Lifestyle and Behavior of Post-Bariatric Surgery and Participants with Obesity: A Community-Based Cross-Sectional Study.

There is a paucity of research dedicated to exploring behavioral change in patients following bariatric surgery. However, there is a need for comparison analysis of individuals with obesity who have received surgical treatment and those who have not opted for any surgical procedures for weight loss. This study is designed to scrutinize the lifestyle choices, behavioral patterns, psychological elements, and eating habits of individuals who have undergone bariatric surgery, in contrast to those with obesity who have not undergone such a procedure. This study is a secondary analysis from Sharik Diet and Health National Survey (SDHNS) dataset, which is a cross-sectional investigation covering the period from 2020 to 2022. The study focused on demographic factors like age, gender, educational attainment, and monthly earnings. Furthermore, other variables such as physical activity, leisure and workplace sitting habits, smoking patterns, strategies for managing weight, and eating and consumption behaviors were also examined. Out of the initial 15,980 participants reached, 4,069 satisfied the study's inclusion criteria. Bariatric surgery was reported by 806 participants (19.8%). Upon comparing three obesity status groups - The participants who underwent bariatric surgery with or without obesity, those with obesity who did not opt for any surgical weight loss measure, the analysis found that the three obesity status groups were significantly different in 21 variables from a total of 26. Moreover, a logistic regression analysis revealed that 11 variables influenced persistent obesity in the post-surgery phase, as opposed to those who successfully lost weight. These variables included advanced age, limited education, being female, lower income, waterpipe smoking habits, and the consumption of carbonated drinks. This study showed that inability to lose weight after bariatric surgery are linked to poor lifestyle choices and behavior compared to those who were able to lose weight after the surgery.

Interactive effects of gestational diabetes and high pre-pregnancy body mass index on adverse growth patterns of offspring.

To examine the independent and interactive effects of maternal gestational diabetes mellitus (GDM) and high pre-pregnancy body mass index (BMI) on the risk of offspring adverse growth patterns. One thousand six hundred and eighty onemother-child pairs were followed for 8years in Tianjin, China. Group-based trajectory modelling was used to identify offspring growth patterns. Logistic regression was performed to obtain odds ratios (ORs) and 95% confidence intervals (CIs) of GDM and high pre-pregnancy BMI for offspring adverse growth patterns. Restricted cubic spline was used to identify cut-off points. Additive interactions and multiplicative interactions were used to test interactive effects between GDM and high pre-pregnancy BMI for adverse growth patterns. Four distinct growth patterns were identified in offspring, including normal growth pattern, persistent lean growth pattern, late obesity growth pattern (LOGP), and persistent obesity growth pattern (POGP). Maternal high pre-pregnancy BMI was associated with LOGP and POGP (adjusted OR, 95% CI: 2.38, 1.74-3.25 & 4.92, 2.26-10.73). GDM greatly enhanced the adjusted OR of high pre-pregnancy BMI for LOGP up to 3.48 (95% CI: 2.25-5.38). Additive interactions and multiplicative interactions between both risk factors were significant for LOGP but not for POGP. Maternal high pre-pregnancy BMI was associated with increased risk of LOGP and POGP, whereas GDM greatly enhanced the risk of high pre-pregnancy BMI for LOGP.

Food security and trajectories of childhood overweight: Results from the Growing Up in Scotland Study

Abstract Background Inequalities in childhood obesity have widened since 2010 in Scotland, raising concerns for future adult and child health. Increasing food insecurity may contribute to the trend, however evidence for an association with childhood overweight is mixed. We estimate the association between food insecurity and trajectories of overweight among primary school aged children in Scotland. Methods Data were from 1824 children in the Growing Up in Scotland Study, a nationally representative cohort born 2004/5. Height and weight were measured at ages 4, 6, 8 and 10 years, and classified as overweight/obese using age and sex standardised cut-offs. Observed trajectories included: never, always, increasing, decreasing, and mixed patterns of overweight (including obesity). Associations between household food insecurity, measured at age 2, and overweight trajectory were estimated using multinomial regression (never overweight as baseline), adjusted for area deprivation, lone parenting, and mother education. Results Most children were never overweight (54.8%), while 12.6% were overweight throughout. Children with high household food insecurity (6.2%) had nearly twice the risk of experiencing persistent overweight (including obesity) than those with no food insecurity (RRR 1.84, 95% CI 1.02-3.30). Additional analysis showed an even larger association for persistent obesity (RRR 2.53, 95% CI 1.06-6.08). Risk of experiencing increasing, decreasing or mixed patterns of overweight were also elevated. Associations were similar for boys and girls. Conclusions Food insecurity is associated with persistent childhood overweight and obesity. The cost-of-living crisis has exacerbated barriers to accessing healthy, nutritious food. Interventions to tackle childhood food security are vital to avoid storing up future health inequalities. Key messages • The cost-of-living crisis is exacerbating food insecurity among UK families. • Food insecurity is associated with persistent overweight and obesity during childhood in Scotland.

A high-sugar diet, but not obesity, reduces female fertility in Drosophila melanogaster.

Obesity is linked to reduced fertility in various species, from Drosophila to humans. Considering that obesity is often induced by changes in diet or eating behavior, it remains unclear whether obesity, diet, or both reduce fertility. Here, we show that Drosophila females on a high-sugar diet become rapidly obese and less fertile as a result of increased death of early germline cysts and vitellogenic egg chambers (or follicles). They also have high glycogen, glucose and trehalose levels and develop insulin resistance in their fat bodies (but not ovaries). By contrast, females with adipocyte-specific knockdown of the anti-obesity genes brummer or adipose are obese but have normal fertility. Remarkably, females on a high-sugar diet supplemented with a separate source of water have mostly normal fertility and glucose levels, despite persistent obesity, high glycogen and trehalose levels, and fat body insulin resistance. These findings demonstrate that a high-sugar diet affects specific processes in oogenesis independently of insulin resistance, that high glucose levels correlate with reduced fertility on a high-sugar diet, and that obesity alone does not impair fertility.

Serum Sulfur-Containing Amino Acids and Risk of Maternal Gestational Diabetes and Adverse Growth Patterns in Offspring.

To estimate associations of sulfur-containing amino acids (SAAs) in the early trimester of pregnancy and gestational diabetes mellitus (GDM) and estimate associations of maternal SAAs with adverse growth patterns in offspring. We established a 1:1 matched case-control study (n = 486) from our cohort of pregnant women, and 401 children were followed up at ages 1 to 8 years. We conducted binary conditional logistic regression to estimate the risk associations of serum SAAs with GDM. Multinomial logistic regression was implemented to explore associations of maternal SAAs with adverse growth patterns in the offspring. High serum methionine and cystine were independently associated with increased GDM risk (OR: 1.92, 95%CI: 1.18-3.13 and 2.69, 1.59-4.53). Conversely, a low level of serum taurine was independently associated with increased GDM risk (2.61, 1.64-4.16). Maternal high cystine and low taurine were also associated with an increased risk of persistent obesity growth pattern (POGP) in offspring (OR: 2.79, 95%CI: 1.09-7.17 and 3.92, 1.11-13.89) and the effect was largely independent of GDM. High serum methionine, cystine and low serum taurine in the early trimester of pregnancy were associated with a greatly increased risk of GDM. Maternal high cystine and low taurine were associated with elevated risk of offspring POGP, largely independent of GDM.

Association of changes in obesity and abdominal obesity status with early-onset colorectal cancer risk: a nationwide population-based cohort study.

The incidence of early-onset colorectal cancer (EO-CRC, diagnosed before 50 years of age) has increased in recent decades. The aim of this study was to investigate the association between changes in obesity status and EO-CRC risk. From a nationwide population-based cohort, individuals <50 years old who participated in the national health checkup program in both 2009 and 2011 were included. Obesity was defined as a body mass index ≥25 kg/m2. Abdominal obesity was defined as a waist circumference ≥ 90 cm in men and ≥ 85 cm in women. Participants were classified into 4 groups according to the change in obesity (normal/normal, normal/obese, obese/normal, persistent obese) and abdominal obesity (normal/normal, normal/abdominal obesity, abdominal obesity/normal, persistent abdominal obesity) status. Participants were followed up until 2019 and censored when they became 50 years old. Among 3,340,635 participants, 7,492 patients were diagnosed with EO-CRC during 7.1 years of follow-up. The risk of EO-CRC was higher in the persistent obesity and persistent abdominal obesity groups than in the normal/normal groups (hazard ratio (HR) [95% confidence interval (CI)] = 1.09 [1.03-1.16] and 1.18 [1.09-1.29], respectively). Participants with both persistent obesity and abdominal obesity had a higher EO-CRC risk than those in the normal/normal groups for both [HR (95% CI) = 1.19 (1.09-1.30)]. Persistent obesity and persistent abdominal obesity before the age of 50 are associated with a slightly increased risk of EO-CRC. Addressing obesity and abdominal obesity in young individuals might be beneficial in reducing the risk of EO-CRC.

373-OR: Repetitive Transcranial Magnetic Stimulation—A Potential Antiobesity Approach for Long-Term Maintenance of Weight Loss

Current anti-obesity interventions result in early rapid weight loss, but long-term maintenance of lost weight is much more challenging. Initial weight loss is typically followed by a weight plateau and progressive regain. We demonstrated the efficacy of repetitive Transcranial Magnetic Stimulation (rTMS) in inducing long-term weight loss (up to 1 year) in individuals with obesity by modulating the brain dopaminergic system and the prefrontal cortex. In a post-hoc analysis, we re-evaluated body weight loss up to 3 years after, in 44 individuals treated with a 5-week high frequency rTMS or sham stimulation, for obesity. Out of 44 subjects, 30 individuals (21 F/9 M, BMI 35.3±2.8, age 49.9±9.3) did not undergo any further weight loss treatments (except diet), 9 subjects (5 F/4 M, BMI 40.4±4.7, age 44.7±.6.1) underwent bariatric surgery, and 5 patients were treated for persistent obesity with a GLP-1 receptor agonist (GLP1-RA) (5 F/0 M, BMI 36.8±6.5, age 53.2±13.9). Out of 30 subject who did not undergo any further weight loss intervention, the 16 patients who received real rTMS (10 F/6 M, BMI 34.6±3.2, age 49.2±7.5) reported a significant body weight loss compared to the Sham group (11 F/3M, BMI 36.1±2.0, age 50.7±2.0) at the end of the 5-week intervention (BMI:-4.5±1.7% vs -1.6±1.8%, p=0.0001). Crucially, they continued to lose body weight compared to the Sham even 3 years after the end of intervention (BMI: -9.5±7.6% vs -3.6±8.4%, p=0.056). As expected, during the 3-year follow-up, bariatric surgery was more effective in promoting weight loss compared to the rTMS and the GLP1-RA (p=0.0001), but rTMS has not been shown to be less effective than GLP1-RA in maintaining lost weight (p=0.621). This preliminary evidence of efficacy of rTMS in promoting long-term weight loss (over one year) may be explained via neuronal neuroplasticity. TMS alone or in combination with other anti-obesity approaches may open new ways to sustain the efficacy of weight control interventions. Disclosure A.Ferrulli: None. S.Massarini: None. C.Macrì: None. P.Senesi: None. I.Terruzzi: None. D.Cannavaro: None. L.Luzi: Advisory Panel; Eli Lilly and Company, Medtronic, Research Support; Gelesis, Speaker's Bureau; A. Menarini Diagnostics, Amgen Inc., Boehringer Ingelheim and Eli Lilly Alliance, Eli Lilly and Company, Novo Nordisk, Novartis. Funding IRCCS MultiMedica (Ricerca Corrente)

The risk of colorectal cancer according to obesity status at four-year intervals: a nationwide population-based cohort study

Obesity is a risk factor for colorectal cancer. However, the effect of body weight change on colorectal cancer is uncertain. This study aimed to investigate the relationship between difference in body mass index and the risk of colorectal cancer. In this nationwide population-based cohort study, participants of the national cancer screening program in 2005 and 2009 were enrolled. Difference of body mass index was calculated from screening data from 2005 and 2009. Participants were divided into four groups according to direction of obesity status: non-obese/non-obese, non-obese/obese, obese/non-obese, and obese/obese. The effect of differences in body mass index on colorectal cancer was analyzed. Among 3,858,228 participants, 47,894 (1.24%) participants were newly diagnosed with colorectal cancer during the 9.2 years of follow-up. The incidence of colorectal cancer was higher in the obese/obese group than the non-obese/non-obese group (hazard ratio = 1.08 [1.06–1.11], P trend < 0.001). The men in the obese/obese group had a higher risk of colon cancer than women (hazard ratio = 1.13 [1.10–1.17] in men, and hazard ratio = 1.04 [1.01–1.18] in women, P = 0.001). Persistent obesity was associated with a higher risk of incidence of colorectal cancer.

Longitudinal weight status and academic achievement in elementary schoolchildren in the United States.

Childhood overweight and obesity have a well-established negative impact on children's health. Overweight and obesity might also negatively impact children's academic performance, but existing literature on this association is inconclusive. This study uses a longitudinal design in a large, diverse elementary school sample to rigorously test the association between longitudinal weight status and academic achievement. Analyses also investigate modification by sex, race/ethnicity, and cardiorespiratory fitness (CRF). In a large suburban school district in the United States, 4936 Grade 4 students were recruited. Demographic, course grade, and standardized test data were collected from school records for Grades 3-5, and body mass index and CRF were assessed each year. Students wore accelerometers during the school day for up to 15 days across three semesters (Grade 4 Fall and Spring, Grade 5 Fall) to objectively measure physical activity. Multiple imputation addressed missing data and multilevel analyses controlled for student demographics and clustering within schools. Unadjusted multilevel models found small negative associations between persistent obesity and course grades and standardized test scores, but these associations largely disappeared when controlling for demographic characteristics. Residual associations for math and writing course grades were attenuated when controlling for CRF, though some marginal negative associations for math and writing remained for students who developed obesity during follow-up. There was also evidence of marginal negative associations with course grades for students who developed overweight/obesity. There was no evidence of modification by sex or race/ethnicity. Results suggest very small associations between weight status and academic achievement that were largely explained by sociodemographic factors and CRF. Evidence of an association between weight status and achievement was stronger among students who developed overweight/obesity. Interventions promoting healthy weight and high CRF remain critical for schools given the link between student health and achievement.

Nutritional Modulation of Associations between Prenatal Exposure to Persistent Organic Pollutants and Childhood Obesity: A Prospective Cohort Study.

Prenatal exposure to persistent organic pollutants (POPs) may contribute to the development of childhood obesity and metabolic disorders. However, little is known about whether the maternal nutritional status during pregnancy can modulate these associations. The main objective was to characterize the joint associations and interactions between prenatal levels of POPs and nutrients on childhood obesity. We used data from to the Spanish INfancia y Medio Ambiente-Environment and Childhood (INMA) birth cohort, on POPs and nutritional biomarkers measured in maternal blood collected at the first trimester of pregnancy and child anthropometric measurements at 7 years of age. Six organochlorine compounds (OCs) [dichlorodiphenyldichloroethylene, hexachlorobenzene (HCB), () and polychlorinated biphenyls 138, 153, 180] and four per- and polyfluoroalkyl substances (PFAS) were measured. Nutrients included vitamins (D, B12, and folate), polyunsaturated fatty acids (PUFAs), and dietary carotenoids. Two POPs-nutrients mixtures data sets were established: a) OCs, PFAS, vitamins, and carotenoids (), and b) OCs, PUFAs, and vitamins (). Joint associations of mixtures on obesity were characterized using Bayesian kernel machine regression (BKMR). Relative importance of biomarkers and two-way interactions were identified using gradient boosting machine, hierarchical group lasso regularization, and BKMR. Interactions were further characterized using multivariate regression models in the multiplicative and additive scale. Forty percent of children had overweight or obesity. We observed a positive overall joint association of both POPs-nutrients mixtures on overweight/obesity risk, with HCB and vitamin B12 the biomarkers contributing the most. Recurrent interactions were found between HCB and vitamin B12 across screening models. Relative risk for a natural log increase of HCB was 1.31 (95% CI: 1.11, 1.54, ) in the tertile 2 of vitamin B12 and in the additive scale a relative excess risk due to interaction of 0.11 (95% CI: 0.02, 0.20) was found. Interaction between perfluorooctane sulfonate and suggested a protective effect of the antioxidant on overweight/obesity risk. These results support that maternal nutritional status may modulate the effect of prenatal exposure to POPs on childhood overweight/obesity. These findings may help to develop a biological hypothesis for future toxicological studies and to better interpret inconsistent findings in epidemiological studies. https://doi.org/10.1289/EHP11258.

Characteristics and outcomes for patients undergoing revisional bariatric surgery due to persistent obesity: a retrospective cohort study of 10,589 patients.

Revisional bariatric surgery in an option for patients who experience weight regain or inadequate weight loss after primary elective bariatric procedures. However, there is conflicting data on safety outcomes of revisional procedures. We aim to characterize patient demographics, procedure type, and safety outcomes for those undergoing revisional compared to initial bariatric interventions to guide management of these patients. The 2020 Metabolic and Bariatric Accreditation and Quality Improvement Program (MBSAQIP) registry was analyzed, comparing primary elective to revisional bariatric procedures for inadequate weight loss. Bivariate analysis was performed to determine between group differences. Multivariable logistic regression determined factors associated with serious complications or mortality. We evaluated 158,424 patients, including 10,589 (6.7%) revisional procedures. Patients undergoing revisional procedures were more like to be female (85.5% revisional vs. 81.0% initial; p < 0.001), had lower body mass index (43.6 ± 7.8kg/m2 revisional vs. 45.2 ± 7.8kg/m2 initial; p < 0.001), and less metabolic comorbidities than patients undergoing primary bariatric surgery. The most common revisional procedures were Roux-en-Y gastric bypass (48.4%) and sleeve gastrectomy (32.5%). Revisional procedures had longer operative duration compared to primary procedures. Patients undergoing revisional procedures were more likely to experience readmission to hospital (4.8% revisional vs. 2.9% initial; p < 0.001) and require reoperation (2.4% revisional vs. 1.0% initial; p < 0.001) within 30days of the procedure. Revisional procedures were independently associated with increased serious complications (OR 1.49, CI 1.36-1.64, p < 0.001) but were not a significant predictor of 30-day mortality (OR 0.74, CI 0.36-1.50, p = 0.409). In comparison to primary bariatric surgery, patients undergoing revisional procedures have less metabolic comorbidities. Revisional procedures have worse perioperative outcomes and are independently associated with serious complications. These data help to contextualize outcomes for patients undergoing revisional bariatric procedures and to inform decision making in these patients.

A natural history study of paediatric non-alcoholic fatty liver disease over 10 years

The long-term outcome of paediatric non-alcoholic fatty liver disease (NAFLD) has not been well established. Between 2008 and 2012, an unselected cohort of 133 children with severe obesity was screened for NAFLD. The aim of this study was to determine the 10-year natural history of NAFLD in this cohort. All 133 participants of the original study were approached. Proton magnetic resonance spectroscopy (1H-MRS) and the Enhanced Liver Fibrosis® (ELF) test were used to assess longitudinal changes in steatosis and fibrosis, respectively. Risk factors for disease progression were explored. Fifty-one of the 133 participants (38%) from the original cohort were included. The mean follow-up time was 10.3 years (range 7-13 years), 65% were female and 92% had persistent obesity. The proportion of participants with steatosis remained unchanged (47%). Nine individuals developed steatosis and in nine individuals steatosis resolved. Predefined relevant individual changes in 1H-MRS were seen in 38% of the participants. The mean ELF test did not change significantly (8.70 ± 0.58 vs. 8.51 ± 0.71, p= 0.22). However, 16% had a relevant increase in ELF test and 6% of those with NAFLD developed advanced fibrosis at follow-up. Changes in steatosis correlated with changes in established metabolic risk factors, alanine aminotransferase, and bariatric surgery. A change in the ELF test was associated with a change in triglycerides. This 10-year follow-up study shows that one-third of the young adults who had childhood obesity develop steatosis and in one-third steatosis resolves. Six percent of those with NAFLD had developed advanced fibrosis at follow-up. These data underscore the importance of screening for NAFLD and monitoring for progression to advanced NAFLD in young people with obesity. Childhood obesity accompanied by fat accumulation in the liver persists into young adulthood in the vast majority, and 6% develop serious liver injury. Worsening of metabolic disturbances increases the risk of liver injury.

Changes in general and abdominal obesity in children at 4, 6 and 9 years of age and their association with other cardiometabolic risk factors

Temporary changes in childhood obesity and their association with cardiometabolic risk factors have been receiving increased attention. The objective of this study was to evaluate changes in general (GO) and abdominal (AO) obesity in children from 4 to 9 years of age and their associations with cardiometabolic risk factors at 9 years of age. This study includes 1344 children from the Longitudinal Childhood Obesity Study (ELOIN). Physical examinations performed at 4, 6 and 9 years of age and a blood sample was only taken at 9 years of age. Changes in obesity from 4 to 9 years of age were estimated using Body Mass Index and waist circumference. Participants were classified into four groups according to GO and AO: (1) stable without obesity (no obesity at all three measurements); (2) remitting obesity at 9 years (obesity at 4 and/or 6 years but not at 9 years); (3) incident or recurrent obesity at 9 years (obesity only at 9 years, at 4 and 9 years or at 6 and 9 years); and (4) stable or persistent with obesity (obesity at 4, 6 and 9 years). Dyslipidemia and dysglycemia were defined by the presence of at least one altered parameter of the lipid or glycemic profile. Odds ratios (OR) were estimated using logistic regression. Compared with children without GO at all ages, those with persistent GO had an OR of 3.66 (95% CI: 2.06–6.51) for dyslipidemia, 10.61 (95% CI: 5.69–19.79) for dysglycemia and 8.35 (95% CI: 4.55–15.30) for high blood pressure. The associations were fairly similar in the case of AO, with ORs of 3.52 (95% CI: 1.96–6.34), 17.15 (95% CI: 9.09–32.34) and 8.22 (95% CI: 4.46–15.15), respectively, when comparing persistent versus stable without AO. Children with incident obesity at 9 years presented a moderate cardiometabolic risk that was nevertheless higher compared to those stable without obesity, whereas those with remitting obesity did not show any significant associations.Conclusion: Incident, and especially, persistent obesity, is associated with an increased cardiometabolic risk. The very early prevention of obesity, with a focus on nutrition, physical activity and sedentary behaviour, as well as tracking growth from birth to age 5, should be a priority to prevent the burden of cardiometabolic disease with consequences for adulthood.What is Known:• General and abdominal obesity has been shown to be associated with other cardiometabolic risk factors such as dyslipidemia, insulin resistance and hypertension.• Temporary changes in obesity and their associations with cardiometabolic risk factors have not been sufficiently explored in childhood.What is New:• Children with incident, and especially persistent, general and/or abdominal obesity, had an increased risk of dyslipidemia, dysglycemia and high blood pressure.•Remitting obesity was not associated with an increased cardiometabolic risk.

Offspring epigenetic markers at birth related to gestational BMI predict offspring BMI-trajectories from infancy to 26years.

To date, epigenetic studies identified differential DNA methylation (DNAm) related to gestational-body mass index (BMI) in offspring at birth. This study investigated whether the identified DNAm in offspring were also associated with BMI trajectories from infancy to age 26years. Data of 794 participants from Isle of Wight birth cohort in UK were investigated to study association between BMI trajectories and DNAm related to gestational-BMI at birth. Multinominal logistic regression models were applied to test the association between 1090 DNAm sites reported in three prior epigenome-wide association studies and BMI trajectories. DNAm site cg23089913 (NANOS1) and cg13217064 (SOX14) were associated with early persistent obesity (EPO) and delayed overweight (DOW) trajectories respectively. A higher methylation of cg23089913 showed low odds of being in EPO trajectory (OR: 0.84; 95% CI: 0.76-0.93) while higher methylation of cg13217064 resulted in 1.4-times the odds of being in DOW trajectory when compared to the normal trajectory [Correction added on 22 February 2023, after first online publication: Range of the DNAm site cg23089913 has been changed from 'lower' to 'higher' in the preceding sentence.]. In a gender-stratified analysis, the odds of developing into DOW was 1.8 times in female participants for cg13217064 while not such association was observed in males. Deviations in methylation of cg23089913 (NANOS1) and cg13217064 (SOX14) in newborns may change the risk of having excess body weight.