Obesity Cohort Research Articles

Obesity-related subclinical hypothyroidism in childhood: Elevated triglycerides but not basal metabolicrate.

Studies on the associations between obesity-related subclinical hypothyroidism with basal metabolic rate and risk factors of cardiovascular disease in children and adolescents are scarce. Retrospective cohort study of children with obesity (n = 294) from the Uppsala Longitudinal Study of Childhood Obesity cohort. Differences in basal metabolic rate quantified by indirect calorimetry, and the cardiovascular risk factors; body mass index, blood lipids, fasting and 2 h oral glucose tolerance test glucose, glycated haemoglobin and insulin resistance, between subjects with and without subclinical hypothyroidism were investigated. The associations of baseline thyroid stimulating hormone (TSH) and ΔTSH with change in cardiovascular risk factors over time were assessed. Subjects with subclinical hypothyroidism had elevated triacylglycerides but no alterations in basal metabolic rate or other measured cardiovascular risk factors. ΔTSH was positively associated with Δtriacylglycerides, Δtotal-cholesterol and ΔLDL-cholesterol, independently of age, sex, Δbody mass index and ΔT4. In the subclinical hypothyroidism group, 92% of individuals normalised their TSH 0.9-2.9 years later. Children with obesity and subclinical hypothyroidism did not have an altered basal metabolic rate but elevated triacylglycerides. During the follow-up period, TSH changed in parallel with several blood lipids. Elevated TSH often normalised without pharmaceutical intervention within 3 years. The present study found that subclinical hypothyroidism in paediatric obesity is related to elevated triglycerides. The present study found that subclinical hypothyroidism is not associated to basal metabolic rate in paediatric obesity. TSH change over time correlated with the change in triglycerides and LDL and total cholesterol. Among subjects with subclinical hypothyroidism at baseline 92% normalised without pharmaceutical intervention within 3 years. This research adds to the knowledge of the longitudinal, natural course of elevated TSH in paediatric obesity which is expected to help to make informed decisions regarding follow-up and evaluation of this patient group.

Evaluation of an oral small-molecule glucagon-like peptide-1 receptor agonist, lotiglipron, for type 2 diabetes and obesity: A dose-ranging, phase 2, randomized, placebo-controlled study.

The aim was to investigate the effects of lotiglipron, a once-daily, oral small-molecule glucagon-like peptide-1 (GLP-1) receptor agonist, in participants with type 2 diabetes (T2D) or obesity. A phase 2, randomized, double-blind, placebo-controlled, dose-ranging study investigated the efficacy and safety of lotiglipron. The study was terminated early for safety reasons after routine data and monitoring review. The planned analyses for the end points were modified prior to unblinding the study. In total, 901 participants were treated with at least one dose of the study drug (T2D cohort: n = 512, obesity cohort: n = 389). Although the majority of participants who were randomly assigned to higher doses did not reach their target maintenance dose, statistically significant changes in HbA1c and body weight were observed. In the T2D cohort, reductions in HbA1c were observed across all lotiglipron doses at week 16 (p < 0.0001), with least squares mean decreases up to -1.44% (90% confidence interval [CI]: -1.63, -1.26) (lotiglipron 80 mg), versus placebo, -0.07% (90% CI: -0.25, 0.11). In the obesity cohort, decreases in body weight were observed across all lotiglipron doses at week 20 (p < 0.01), up to -7.47% (90% CI: -8.50, -6.43) (lotiglipron 200 mg, five-step titration), versus placebo, -1.84% (90% CI: -2.85, -0.83). Across cohorts, the most frequently reported treatment-emergent adverse events were gastrointestinal related (most mild to moderate severity), with nausea being the most common (ranging from 4% [placebo] to 28.8% [80 mg] in the T2D cohort and 12.5% [placebo] to 60.6% [200 mg, four-step titration] in the obesity cohort). Transaminase elevations were observed in a subset of participants (6.6% and 6.0% of participants on lotiglipron in the T2D and obesity cohorts, respectively, compared with 1.6% on placebo in the obesity cohort). The efficacy (HbA1c and/or body weight) of a range of lotiglipron doses was demonstrated in T2D and obesity cohorts. The safety profile was largely consistent with what has been previously known about the mechanism of action. Our results are unique in reporting elevations in liver transaminases in a subset of participants treated with lotiglipron, with attempts to identify the at-risk population unsuccessful and therefore clinical development of lotiglipron terminated. GOV: NCT05579977.

Steatotic Liver Disease in Pediatric Obesity and Increased Risk for Youth-Onset Type 2 Diabetes.

To assess 1) the association between metabolic dysfunction-associated steatotic liver disease (MASLD) in pediatric obesity and youth-onset type 2 diabetes, 2) the joint effect of MASLD and intermediate hyperglycemia on type 2 diabetes risk, and 3) the effect of obesity treatment on type 2 diabetes risk. A cohort study using the Swedish Childhood Obesity Treatment Register (Barnobesitas Registret i Sverige [BORIS]) (1999-2020) linked with national registers was conducted. We included 10,346 children with overweight or obesity and 59,336 matched control individuals. MASLD was defined by transaminases and diagnosis code, separately. Type 2 diabetes was ascertained from national registers. In the obesity cohort, median age at type 2 diabetes diagnosis was 16.9 (quartile 1 [Q1], quartile 3 [Q3]: 14.7, 21.4) years, median follow-up was 8.1 (Q1, Q3: 5.1, 11.7) years. Cumulative incidence of type 2 diabetes at age 30 was 22.7% (obesity and MASLD), 9.9% (obesity alone), and 0.7% (control individuals). MASLD was associated with risk for type 2 diabetes (hazard ratio [HR] 2.71 [95% CI 2.14-3.43]), independently of age, sex, degree of obesity, intermediate hyperglycemia, and parental type 2 diabetes. Joint effect of MASLD and intermediate hyperglycemia increased type 2 diabetes risk (HR 9.04 [6.38-12.79]). Optimal response in obesity treatment reduced the risk (HR 0.23 [0.09-0.57]). MASLD, defined by transaminases or diagnosis code, in pediatric obesity is associated with increased risk for youth-onset type 2 diabetes. MASLD interacts synergistically with intermediate hyperglycemia to dramatically increase the risk. Optimal response in obesity treatment reduces type 2 diabetes risk, despite MASLD.

Prenatal exposure to phthalates and childhood wheeze and asthma in the PROGRESS cohort

IntroductionPrenatal phthalate exposure may influence lung development and lead to wheezing and asthma in childhood, and these associations may vary by sex. Despite ubiquity of exposure, there is limited epidemiologic data on these associations in Latin America. MethodsWe assessed 593 mother-child dyads enrolled in the Programming Research in Obesity, Growth, Environment, and Social Stressors birth cohort in Mexico City. We quantified 15 phthalate metabolites in 2nd and 3rd trimester maternal urine. Report of ever wheeze, wheeze in the past 12 months (current wheeze) and ever asthma were obtained using a validated survey when children were 4 and 6 years of age. We examined individual associations with modified Poisson models. Mixture effects were assessed using Bayesian Weighted Quantile Sum (BWQS) regression. All models were adjusted for child's sex, maternal age and education at enrollment, and parity. ResultsIn Poisson models, a doubling of mono (carboxy-isononyl) phthalate (MCNP) during the 2nd trimester was associated with higher risk of wheeze (RR: 1.14, 95 % CI: 1.01, 1.29), and asthma (RR: 1.44, 95 % CI: 1.05, 1.97) at 4 years of age. Higher concentrations of the sum of di-isononyl phthalate metabolites (∑DiNP) during the 2nd trimester were also associated with asthma at 4 years of age (RR: 1.30, 95 % CI: 1.04, 1.61). Mixture associations of phthalate metabolite concentrations during the 2nd trimester and asthma at 4 years of age were stronger in males (BWQS, OR: 1.94, 95 % CI: 0.90, 4.60; 90 % CrI: 1.04, 3.73) compared to females (BWQS, OR: 1.23, 95 % CI: 0.56, 2.88; 90 % CrI: 0.61, 2.55). Additionally, we observed stronger inverse associations between prenatal phthalate mixtures during the 3rd trimester and current wheeze at 4 and 6 years of age in females (BWQS, OR: 0.54, 90 % CrI: 0.35, 0.82; OR: 0.45, 90 % CrI: 0.22, 0.84) compared to males (BWQS, OR: 0.95, 90 % Cri: 0.68, 1.35; OR: 0.97, 90 % CrI: 0.59, 1.54). ConclusionsPrenatal phthalate metabolite concentrations were associated with respiratory outcomes in childhood, with some evidence of sex specific effects. Future work investigating phthalate exposure and wheeze trajectories/lung function will be important for understanding how these may predict later disease.

Prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances and childhood bone mineral density: A prospective birth cohort study

Background and aimPerfluoroalkyl and polyfluoroalkyl substances (PFAS) have demonstrated potential toxicity in skeletal development. However, the relationship between prenatal PFAS exposure and offspring bone health remains unclear in epidemiological studies. Therefore, we aim to investigate whether prenatal exposure to PFAS is associated with bone mineral density (BMD) in offspring. MethodThis study population included 182 mother-child pairs in the Shanghai Obesity and Allergy Cohort, enrolled during 2012–2013. 10 PFAS were measured by liquid chromatography-mass spectrometry (LC-MS) in cord plasma. The child's spinal BMD was measured using a dual-energy X-ray absorptiometry (DXA) scanner at the age of 8. Multivariable linear regression models were used to estimate the associations between individual PFAS concentrations (as a continuous variable or categorized into quartiles) and child BMD. Bayesian kernel machine regression (BKMR) was employed to explore the joint effects of PFAS mixtures on BMD. ResultsAmong the 10 PFAS, 8 of them had a detection rate >90% and were included in the subsequent analysis. We observed no significant associations between individual PFAS (as a continuous variable) and spinal BMD in 8-year-old children using the multivariable linear regression model. When treated as quartile categories, the second and fourth quartiles of perfluorobutane sulfonate (PFBS) was associated with higher BMD in the first lumbar vertebra, compared with the lowest quartile. BKMR analysis revealed no association between the PFAS mixture and child BMD. ConclusionWe observed no associations of prenatal PFAS exposure with child BMD at 8 years of age. Given the inconsistent epidemiological evidence, further research is needed to confirm these findings from other studies or elucidate the potentially toxic effects of PFAS on bone.

Prenatal and early life exposure to fine particulate matter and telomere length in early childhood

BackgroundTelomere length is a biomarker of molecular aging that may be impacted by air pollution exposure starting in utero. We aimed to examine the association between prenatal and early life exposure to fine particulate matter (PM2.5) and leukocyte telomere length (LTL) in children and explore sex differences. MethodsAnalyses included 384 mother–child pairs enrolled in the Programming Research in Obesity, Growth, and Environmental Stressors (PROGRESS) birth cohort in Mexico City. Exposure to PM2.5 was estimated at the residential level using a satellite based spatio-temporally resolved prediction model. Average relative LTL was measured in DNA isolated from blood collected at age 4–6 years using quantitative real-time polymerase chain reaction. Linear regression models were used to examine the association between average PM2.5 across pregnancy, individual trimesters, first postnatal year, and LTL. Models were adjusted for maternal age and education at enrollment, prenatal environmental tobacco smoke exposure, child sex, age, and body mass index z-score at LTL measurement. Effect modification by sex was investigated with interaction terms and stratification. ResultsIn trimester specific models, we found an association between 2nd trimester PM2.5 and elongated LTL (β: 4.34, 95%CI [0.42, 8.42], per 5 μg/m3 increase). There was suggestive effect modification by sex on average 2nd trimester PM2.5 with stronger associations seen in females compared to males (β: 7.12, [95%CI: 0.98, 13.6] and β: 1.43 [95%CI: −3.46, 6.57]) per 5 μg/m3 increase respectively. ConclusionSecond trimester PM2.5 levels were associated with changes in LTL in early childhood. Understanding temporal and sex differences in PM2.5 exposure may provide insights into telomere dynamics over early life.

Prevalence of cardiovascular events among transgender adults with obesity: A population-based analysis

IntroductionAlthough obesity and its impact on cardiovascular (CV) events have been extensively studied in the cisgender population, little is known about its impact on CV events in transgender individuals. Our study aimed to establish the prevalence of obesity and CV events in transgender adults. MethodsWe conducted a retrospective cohort comparative study utilizing the U.S. National Inpatient Sample 2020 database. We identified admissions of transgender patients with administrative codes. Later, these patients were divided into obesity and non-obesity cohorts. Multivariable regression analysis was then performed for in-hospital all-cause mortality, acute myocardial infarction, acute ischemic stroke, cardiac arrest, pulmonary embolism and, major adverse cardiovascular and cerebrovascular events (MACCE). ResultsIn 2020, 19,345 transgender patients were admitted; 16,390 (84.7 %) had no obesity, and 2,955 (15.3 %) had obesity. The median age was 31 years in the non-obesity cohort and 37 years in the obesity cohort. Transgender men comprised 54.5 % of the non-obesity cohort and 47.9 % of the obesity cohort. Common baseline conditions in the non-obesity and obesity cohorts, respectively, included hypertension (20.7 % vs. 43.5 %), diabetes (10.2 % vs. 32.5 %), chronic pulmonary disease (18.9 % vs. 27.7 %), and hyperlipidemia (11.5 % vs. 25 %). MACCE was observed in 2.3 % of the non-obesity cohort compared to 5.4 % in the obesity cohort, and cardiac arrest occurred in 0.2 % of the non-obesity cohort versus 1.2 % in the obesity cohort. A statistically significant association was found in MACCE [odds ratio (OR) 2.1, 95 % confidence interval (CI) 1.24–3.55, p = 0.006] and cardiac arrest [OR 3.92, 95 % CI 1.11–12.63, p = 0.022] among transgender patients with obesity. ConclusionWe observed increased odds of MACCE and cardiac arrest in transgender patients with obesity, possibly due to obesity and CV risk factors like hypertension, diabetes, and hyperlipidemia. Further large-scale comparative studies are needed to better understand obesity's impact on CV outcomes in the transgender population.

The risk of herpes zoster is positively associated with obesity, especially morbid obesity

This study aimed to investigate the association between obesity and herpes zoster (HZ) occurrence. This study used data covering 2 million people in Taiwan in 2000, which were obtained from the National Health Insurance Research Database. The cohort study observed aged 20–100 years with obesity from 2000 to 2017 (tracking to 2018). Obesity was indicated by the presence of two or more outpatient diagnoses or at least one admission record. And, obesity was categorized into non-morbid obesity and morbid obesity. Patients with HZ before the index date were excluded. The obesity cohort and control cohort were matched 1:1 according to age, sex, comorbidities, and index year. There were 18,855 patients in both the obesity and control cohorts. The obesity cohort [adjusted hazard ratio (aHR) 1.09] had a higher risk of HZ than the control cohort. Further analysis, the morbid obesity group (aHR 1.47), had a significantly higher risk of HZ than the non-morbid obesity group. Among the patients without any comorbidities, the patients with obesity had a significantly higher risk of developing HZ than the patients without obesity (aHR 1.18). Obese patients are at a higher risk of HZ development, especially in the patients with morbid obesity. Weight reduction is critical for preventing the onset of chronic diseases and decreasing the risk of HZ in patients with obesity.

Bariatric surgery patients have 5-year risk of revision following total shoulder arthroplasty comparable to that of class III obesity patients

BackgroundObesity has been correlated with heightened risk of complications after orthopedic surgeries. Bariatric surgery (BS) is an effective tool commonly utilized for the reduction of body mass index. However, the impact of BS on complications in total shoulder arthroplasty (TSA) remains inadequately investigated. This study examines the 5-year risk of revision following TSA in patients with a history of BS compared to matched cohorts without history of BS. MethodsUtilizing the PearlDiver Mariner database, a retrospective cohort analysis was conducted on over 157 million U.S. patients from January 2010 to October 2021. Inclusion criteria identified patients undergoing primary TSA with a minimum 2-year follow-up. Propensity-score matching was employed to control for covariates, comparing BS patients with a matched control and a matched class III obesity control without history of BS. Demographics, comorbidities, and outcomes, including 5-year cumulative incidence of revision were analyzed. ResultsThe 5-year cumulative incidence of all-cause revision within the BS group was found to be 4.6%. While this represented a higher risk than that of the general population (hazard ratio 1.70; 95% confidence interval 1.21-2.39), there was no significant difference when compared to controls with class III obesity. The BS cohort had higher risk of revision secondary to dislocation/subluxation and rotator cuff tear than in the general population. When compared to the class III obesity cohort, only the risk of revision due to rotator cuff tear was found to be higher. ConclusionIndividuals with a history of BS showed a higher risk of revision than a cohort without history of BS and an equivalent risk of revision compared to a cohort of class III obesity controls after undergoing TSA. Though obesity is an important risk factor for complications after TSA, BS might not be an effective tool for preoperative risk optimization.

#1382 Kidney outcomes after bariatric surgery: a population-based cohort study

Abstract Background and Aims Obesity is associated with nephrolithiasis, chronic kidney disease (CKD), and kidney failure. Bariatric surgeries, including Roux en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), are effective treatments of severe obesity and may mitigate obesity-related kidney diseases such as CKD and kidney failure, but could on the other hand induce hyperoxaluria and nephrolithiasis, posing a potential risk to the kidneys. We examined the risk of nephrolithiasis, acute kidney injury (AKI), CKD, and kidney failure after bariatric surgery. Method We included individuals undergoing bariatric surgery (RYGB or SG) in Denmark between 2006 and 2018 using population-based registries. These individuals were age- and sex-matched 1:5 to a background general population cohort and a cohort with hospital-diagnosed obesity. Nephrolithiasis was identified by diagnosis codes within the Danish National Patient Registry (DNPR). AKI was defined as an increase in serum creatinine (sCr) of ≥26.5 µmol/L within 48 hours or a relative increase of ≥1.5 times within seven days or from a median outpatient baseline value. CKD was defined as the presence of two outpatient eGFR samples below 60 ml/min/1.73 m2, with a minimum interval of three months between each measurement. Kidney failure was defined by recordings of kidney transplantation or chronic dialysis in DNPR. One- and ten-year cumulative incidences (risks) were computed for each cohort accounting for the competing risk of death. Rates of incident nephrolithiasis, AKI, incident CKD, and incident kidney failure in post-bariatric-surgery patients were compared with the background population cohort and obesity cohort using multivariable Cox regression adjusting for age, sex, and Charlson Comorbidity Index (CCI)-score. Results We included 18,827 individuals with bariatric surgery (17,200 with RYGB and 1,627 with SG). Median follow-up was 8.1 years (5.2-9.2), 8.0 years (4.6-9.1), and 7.9 years (4.2-9.1) for the overall bariatric cohort, the background population cohort, and the obesity cohort, respectively. Within the bariatric cohort, the ten-year risk of nephrolithiasis was 2.8%, the one-year risk of AKI was 2.7%, while the ten-year risks of CKD, and kidney failure were 0.2% and 0.1%, respectively. When comparing the post-bariatric-surgery cohort with the general population cohort, the adjusted hazard ratio (HR) was 2.92 (95% CI; 2.61, 3.27) for nephrolithiasis, 2.60 (95% CI; 2.06, 3.28) for AKI, 0.36 (95% CI; 0.18, 0.73) for CKD, and 0.81 (95% CI; 0.49, 1.32) for kidney failure. Compared with the obesity cohort, the adjusted HRs for adverse events were at 1.73 (95% CI: 1.56, 1.91) for nephrolithiasis, 1.63 (95% CI; 1.38, 1.92) for AKI, 0.41 (95% CI; 0.26, 0.66) for CKD, and 0.65 (95% CI; 0.42, 0.98) for kidney failure. Conclusion Individuals with bariatric surgery had a higher ten-year rate of nephrolithiasis and a higher one-year rate of AKI, but reduced rates of CKD and kidney failure within ten years after surgery compared with both the background cohort and the obesity cohort.

Genetic determinants of serum bilirubin using inferred native American gene variants in Chilean adolescents.

Gene variants in the UGT1A1 gene are strongly associated with circulating bilirubin levels in several populations, as well as other variants of modest effect across the genome. However, the effects of such variants are unknown regarding the Native American ancestry of the admixed Latino population. Our objective was to assess the Native American genetic determinants of serum bilirubin in Chilean admixed adolescents using the local ancestry deconvolution approach. We measured total serum bilirubin levels in 707 adolescents of the Chilean Growth and Obesity Cohort Study (GOCS) and performed high-density genotyping using the Illumina-MEGA array (>1.7 million genotypes). We constructed a local ancestry reference panel with participants from the 1000 Genomes Project, the Human Genome Diversity Project, and our GOCS cohort. Then, we inferred and isolated haplotype tracts of Native American, European, or African origin to perform genome-wide association studies. In the whole cohort, the rs887829 variant and others near UGT1A1 were the unique signals achieving genome-wide statistical significance (b = 0.30; p = 3.34 × 10-57). After applying deconvolution methods, we found that significance is also maintained in Native American (b = 0.35; p = 3.29 × 10-17) and European (b = 0.28; p = 1.14 × 10-23) ancestry components. The rs887829 variant explained a higher percentage of the variance of bilirubin in the Native American (37.6%) compared to European ancestry (28.4%). In Native American ancestry, carriers of the TT genotype of this variant averaged 4-fold higher bilirubinemia compared to the CC genotype (p = 2.82 × 10-12). We showed for the first time that UGT1A1 variants are the primary determinant of bilirubin levels in Native American ancestry, confirming its pan-ethnic relevance. Our study illustrates the general value of the local ancestry deconvolution approach to assessing isolated ancestry effects in admixed populations.

Time-specific impact of trace metals on breast density of adolescent girls in Santiago, Chile.

Whether trace metals modify breast density, the strongest predictor for breast cancer, during critical developmental stages such as puberty remains understudied. Our study prospectively evaluated the association between trace metals at Tanner breast stage B1 (n = 291) and at stages both B1 and B4 (n = 253) and breast density at 2 years post-menarche among Chilean girls from the Growth and Obesity Cohort Study. Dual-energy x-ray absorptiometry assessed the volume of dense breast tissue (absolute fibroglandular volume [FGV]) and percent breast density (%FGV). Urine trace metals included arsenic, barium, cadmium, cobalt, cesium, copper, magnesium, manganese, molybdenum, nickel, lead, antimony, selenium, tin, thallium, vanadium, and zinc. At B1, a doubling of thallium concentration resulted in 13.69 cm3 increase in absolute FGV (β: 13.69, 95% confidence interval [CI]: 2.81, 24.52), while a doubling of lead concentration resulted in a 7.76 cm3 decrease in absolute FGV (β: -7.76, 95%CI: -14.71, -0.73). At B4, a doubling of barium concentration was associated with a 10.06 cm3 increase (β: 10.06, 95% CI: 1.44, 18.60), copper concentration with a 12.29 cm3 increase (β: 12.29, 95% CI: 2.78, 21.56), lead concentration with a 9.86 cm3 increase (β: 9.86, 95% CI: 0.73, 18.98), antimony concentration with a 12.97 cm3 increase (β: 12.97, 95% CI: 1.98, 23.79) and vanadium concentration with a 13.14 cm3 increase in absolute FGV (β: 13.14, 95% CI: 2.73, 23.58). Trace metals may affect pubertal breast density at varying developmental stages with implications for increased susceptibility for breast cancer.

Obesity is Associated with Increased Risk of New-Onset Chronic Rhinosinusitis: A United States Population-Based Cohort Study.

The aim of this study was to determine the risk of a new-encounter diagnosis of unspecified chronic rhinosinusitis (CRS), CRS with nasal polyps (CRSwNP), and eosinophilic granulomatosis with polyangiitis (EGPA) 1 and 2 years following body mass index (BMI) classification of obesity utilizing a large-population-based analytics platform. Retrospective cohort analysis SETTING: The U.S. Collaborative Network within the TriNetX Analytics platform contains deidentified electronic health record (EHR) data of more than 100 million patients and was used to determine the association between obesity and a new encounter diagnosis of 3 CRS phenotypes in this study. After 1:1 propensity score matching, patients with an overweight BMI and obesity were at a higher risk for a new-encounter diagnosis of unspecified CRS and CRSwNP compared to healthy-weight individuals. The obesity cohort had the greatest increased risk of new-onset unspecified CRS with a relative risk of 1.23 (95% CI: 1.20-1.25) and 1.26 (95% CI: 1.24-1.28) 1 and 2 years following BMI classification, respectively. Our study indicates an association between obesity and new-onset unspecified CRS and CRSwNP. With the increasing prevalence of obesity in the United States population, it will be important to understand how obesity-associated CRS may affect treatment response. Future prospective studies are needed to assess causality and define a mechanistic link.

Breast composition during and after puberty: the Chilean Growth and Obesity Cohort Study

BackgroundBreast density (BD) is a strong risk factor for breast cancer. Little is known about how BD develops during puberty. Understanding BD trajectories during puberty and its determinants could be crucial for promoting preventive actions against breast cancer (BC) at early ages. The objective of this research is to characterize % fibroglandular volume (%FGV), absolute fibroglandular volume (AFGV), and breast volume (BV) at different breast Tanner stages until 4-year post menarche in a Latino cohort and to assess determinants of high %FGV and AFGV during puberty and in a fully mature breast.MethodsThis is a longitudinal follow-up of 509 girls from low-middle socioeconomic status of the Southeast area of Santiago, recruited at a mean age of 3.5 years. The inclusion criteria were singleton birth born, birthweight between 2500 and 4500 g with no medical or mental disorder. A trained dietitian measured weight and height since 3.5 years old and sexual maturation from 8 years old (breast Tanner stages and age at menarche onset). Using standardized methods, BD was measured using dual-energy X-ray absorptiometry (DXA) in various developmental periods (breast Tanner stage B1 until 4 years after menarche onset).ResultsIn the 509 girls, we collected 1,442 breast DXA scans; the mean age at Tanner B4 was 11.3 years. %FGV increased across breast Tanner stages and peaked 250 days after menarche. AFGV and BV peaked 2 years after menarche onset. Girls in the highest quartiles of %FGV, AFGV, and BV at Tanner B4 and B5 before menarche onset had the highest values thereafter until 4 years after menarche onset. The most important determinants of %FGV and AFGV variability were BMI z-score (R2 = 44%) and time since menarche (R2 = 42%), respectively.ConclusionWe characterize the breast development during puberty, a critical window of susceptibility. Although the onset of menarche is a key milestone for breast development, we observed that girls in the highest quartiles of %FGV and AFGV tracked in that group afterwards. Following these participants in adulthood would be of interest to understand the changes in breast composition during this period and its potential link with BC risk.

Relation between Body Composition Trajectories from Childhood to Adolescence and Nonalcoholic Fatty Liver Disease Risk.

NAFLD has become the leading cause of chronic liver disease in children, as a direct consequence of the high prevalence of childhood obesity. This study aimed to characterize body composition trajectories from childhood to adolescence and their association with the risk of developing nonalcoholic fatty liver disease (NAFLD) during adolescence. The participants were part of the 'Chilean Growth and Obesity Cohort Study', comprising 784 children who were followed prospectively from age 3 years. Annual assessments of nutritional status and body composition were conducted, with ultrasound screening for NAFLD during adolescence revealing a 9.8% prevalence. Higher waist circumference measures were associated with NAFLD from age 3 years (p = 0.03), all skin folds from age 4 years (p < 0.01), and DXA body fat measurements from age 12 years (p = 0.01). The fat-free mass index was higher in females (p = 0.006) but not in males (p = 0.211). The second and third tertiles of the fat mass index (FMI) had odds ratios for NAFLD during adolescence of 2.19 (1.48-3.25, 95% CI) and 6.94 (4.79-10.04, 95% CI), respectively. Elevated waist circumference, skin folds, and total body fat were identified as risk factors for future NAFLD development. A higher FMI during childhood was associated with an increased risk of NAFLD during adolescence.

No Difference in Revision Rates up to 10 years Following Total Hip Arthroplasty in Patients Who Had Prior Bariatric Surgery When Compared to Patients Who Had Class III Obesity: A Propensity Matched Analysis

BackgroundThere is no clear research showcasing bariatric surgery’s (BS’s) impact on long-term surgical complications following total hip arthroplasty (THA). Therefore, this study compared the 10-year cumulative incidence and risk of revision following THA in patients who underwent BS when compared to the general population and class III obesity patients who did not undergo BS. MethodsPatients who underwent elective THA from 2010 to 2021 were identified using an all-payer claims database. Patients who underwent BS prior to THA were separately matched to a control of the general population and those who had class III obesity (body mass index ≥40) by age, sex, Charlson Comorbidity Index, and diabetes using a 1:4 ratio. Kaplan-Meier analyses generated 10-year cumulative incidence rates, and a Cox proportional hazard ratio (HR) model generated HRs and 95% confidence intervals (CIs). ResultsWhen compared to the general control, patients who have a history of BS had an elevated 10-year risk of all-cause revision (HR 1.31, 95% CI: 1.16 to 1.47, P < .001), prosthetic joint infection (HR: 1.62, CI: 1.30 to 2.04; P < .001), mechanical loosening (HR: 1.20, CI: 1.01 to 1.44; P = .040), and dislocation/instability (HR: 1.35, CI: 1.09 to 1.68; P = .007). There was no difference in the 10-year risk of all-cause revision or other indications for revision in the BS cohort compared to the matched class III obesity cohort (P = .142). ConclusionsThose who underwent BS before THA had comparable 10-year revision rates when compared to those who had class III obesity and higher rates compared to the general population. This suggests BS may not reduce the 10-year surgical risks associated with obesity when compared to a class III obese surgical population.

Claudin-1 as a novel target gene induced in obesity and associated to inflammation, fibrosis, and cell differentiation.

T lymphocytes from visceral and subcutaneous white adipose tissues (vWAT and sWAT, respectively) can have opposing roles in the systemic metabolic changes associated with obesity. However, few studies have focused on this subject. Claudin-1 (CLDN1) is a protein involved canonically in tight junctions and tissue paracellular permeability. We evaluated T-lymphocyte gene expression in vWAT and sWAT and in the whole adipose depots in human samples. A Clariom D-based transcriptomic analysis was performed on T lymphocytes magnetically separated from vWAT and sWAT from patients with obesity (Cohort 1; N = 11). Expression of candidate genes resulting from that analysis was determined in whole WAT from individuals with and without obesity (Cohort 2; patients with obesity: N = 13; patients without obesity: N = 14). We observed transcriptional differences between T lymphocytes from sWAT compared with vWAT. Specifically, CLDN1 expression was found to be dramatically induced in vWAT T cells relative to those isolated from sWAT in patients with obesity. CLDN1 was also induced in obesity in vWAT and its expression correlates with genes involved in inflammation, fibrosis, and adipogenesis. These results suggest that CLDN1 is a novel marker induced in obesity and differentially expressed in T lymphocytes infiltrated in human vWAT as compared with sWAT. This protein may have a crucial role in the crosstalk between T lymphocytes and other adipose tissue cells and may contribute to inflammation, fibrosis, and alter homeostasis and promote metabolic disease in obesity.

Oligogenic inheritance in severe adult obesity.

The genetic architecture of extreme non-syndromic obesity in adults remains to be elucidated. A range of genes are known to cause monogenic obesity, but even when pathogenic mutations are present, there may be variable penetrance. Whole-exome sequencing (WES) was carried out on a 15-year-old male proband of Pakistani ancestry who had severe obesity. This was followed by family segregation analysis, using Sanger sequencing. We also undertook re-analysis of WES data from 91 unrelated adults with severe obesity (86% white European ancestry) from the Personalised Medicine for Morbid Obesity (PMMO) cohort, recruited from the UK National Health Service. We identified an oligogenic mode of inheritance of obesity in the proband's family-this provided the impetus to reanalyze existing sequence data in a separate dataset. Analysis of PMMO participant data revealed two further patients who carried more than one rare, predicted-deleterious mutation in a known monogenic obesity gene. In all three cases, the genes involved had known autosomal dominant inheritance, with incomplete penetrance. Oligogenic inheritance may explain some of the variable penetrance in Mendelian forms of obesity. We caution clinicians and researchers to avoid confining sequence analysis to individual genes and, in particular, not to stop looking when the first potentially-causative mutation is found.

Prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) in a middle-aged population with overweight and normal liver enzymes, and diagnostic accuracy of noninvasive proxies.

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing at an alarming rate. Elevated liver enzymes are a primary reason to refer patients for further testing. However, liver enzymes within the normal range do not exclude the presence of MASLD. We examined the prevalence of MASLD in a middle-aged population with overweight and normal liver enzymes. In addition, we examined the accuracy of 4 sets of noninvasive proxies for MASLD. We included 1017 participants from the Netherlands epidemiology of obesity cohort study with body mass index ≥25 kg/m2 and liver enzymes (asparate aminotransferase, alanine aminotransferase, gamma-glutamyltranspeptidase) within normal range. The diagnostic accuracy of biomarker scores (fatty liver index, liver fat score [LFS], STEATO-ELSA, and hepatic steatosis index) was determined against elevated hepatic triglyceride content measured by 1proton magnetic resonance spectroscopy. Participants (mean age 56 years, 49% women), had a median body mass index of 29.6 kg/m2 and a median hepatic triglyceride content of 4.4%. MASLD was present in 42% of participants and was more common in men than women, with respectively 47% and 36% being affected. The LFS showed the highest accuracy with an area under the curve of 0.72. We identified metabolic syndrome as the prime predictor for MASLD with an odds ratio of 2.95 (95% confidence interval 2.20-3.98). The prevalence of MASLD in middle-aged men and women with overweight and liver enzymes within the normal range is over 40%. LFS showed the highest accuracy to detect MASLD, but, overall, biomarker scores performed relatively poor. The presence of metabolic syndrome was the prime predictor of MASLD.

Longitudinal associations between early-life fluoride exposures and cardiometabolic outcomes in school-aged children

Background/AimFluoride is a natural mineral present in food, water, and dental products, constituting ubiquitous long-term exposure in early childhood and across the lifespan. Experimental evidence shows fluoride-induced lipid disturbances with potential implications for cardiometabolic health. However, epidemiological studies are scarce. For the first time, we evaluated associations between repeated fluoride measures and cardiometabolic outcomes in children. MethodsWe studied ∼ 500 Mexican children from the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) cohort with measurements on urinary fluoride at age 4, and dietary fluoride at ages 4, 6, and 8 years approximately. We used covariate-adjusted linear mixed-effects and linear regression models to assess fluoride associations with multiple cardiometabolic outcomes (ages 4–8): lipids (total cholesterol, HDL, LDL, and triglycerides), glucose, HbA1c, adipokines (leptin and adiponectin), body fat, and age- and sex-specific z-scores of body mass index (zBMI), waist circumference, and blood pressure. ResultsDietary fluoride intake at age 4 was associated with annual increases in triglycerides [β per-fluoride-doubling = 2.02 (95 % CI: 0.37, 3.69)], cholesterol [β = 1.46 (95 % CI: 0.52, 2.39)], HDL [β = 0.39 (95 % CI: 0.02, 0.76)], LDL [β = 0.87 (95 % CI: 0.02, 1.71)], and HbA1c [β = 0.76 (95 % CI: 0.28, 1.24)], and decreased leptin [β = -3.58 (95 % CI: −6.34, −0.75)] between the ages 4 and 8. In cross-sectional analyses at age 8, higher tertiles of fluoride exposure were associated with increases in zBMI, triglycerides, glucose, and leptin (p-tertile trend < 0.05). Stronger associations were observed in boys at year 8 and in girls prior to year 8 (p-sex interaction < 0.05). Fewer but consistent associations were observed for urinary fluoride at age 4, indicating increased annual changes in HDL and HbA1c with higher fluoride levels. ConclusionDietary fluoride exposures in early- and mid-childhood were associated with adverse cardiometabolic outcomes in school-aged children. Further research is needed to elucidate whether these associations persist at later ages.