Obesity最新文献

Objective

Pair-feeding is a study design element where one group's food intake is provided to another group to assess whether a treatment effect is independent of food intake. Investigators often assume equivalent food intake across experimental conditions and exclude it from the statistical analysis. However, the impact of this practice on type I error (T1Er) rates has not been quantified.

Methods

We conducted a Monte Carlo simulation in which animals were assigned baseline weights and food intakes, then randomized to non-pair-fed or pair-fed groups. Daily food intake for both groups was initially drawn from the baseline food intake distribution. For pair-fed animals, food intake was truncated if it exceeded the previous day's intake of the matched non-pair-fed animal (individual pair-feeding) or the group's average (group pair-feeding). Weight changes were calculated as a function of food intake, and final weight change was analyzed with and without adjusting for mean food intake.

Results

Both individual and group pair-feeding inflated T1Er rates ranging from 0.12 to 0.71 in unadjusted models. However, adjustment for food intake reduced error rates to around 0.05.

Conclusions

Under some circumstances, pair-feeding designs can inflate T1Er rates. Investigators can mitigate this inflation by adjusting the analyses for food intake.

Objective

We investigated the impact of sex on the subcutaneous adipose tissue (AT) transcriptome and its obesity-related adaptations.

Methods

We studied rare BMI-discordant monozygotic twin pairs (ΔBMI > 2.5 kg/m²; 21 female, 16 male pairs) to assess how sex affects AT and whole-body metabolism. AT RNA sequencing was analyzed using linear mixed modeling and pathway enrichment for: (1) sex differences in individual twins, adjusted for BMI, (2) sex-stratified effects of acquired obesity (ΔBMI between co-twins separately in females and males), (3) sex-specific effects of obesity (differences in the ΔBMI effect between sexes).

Results

(1) AT transcriptional profiles differed between sexes, associating with insulin sensitivity. (2) Sex-stratified obesity effects within pairs were stronger in females, with upregulated inflammation and downregulated mitochondrial oxidative phosphorylation; males showed increased inflammation and decreased histone modification. (3) The response to obesity was sex-specific: lower expression of genes in unsaturated fatty acid metabolism in obesity was seen in females only. Sex-specific obesity AT gene expression was associated with metabolic health, with a negative association between unsaturated fatty acid metabolism and insulin sensitivity in males only.

Conclusions

Biological sex influences the AT transcriptome and its response to obesity, highlighting distinct molecular mechanisms that may contribute to sex-specific metabolic health.

Objective

This study aimed to quantify the effect of glucagon-like peptide-1 receptor agonists (GLP-1s) on weight loss and weight gain following GLP-1 discontinuation.

Methods

This retrospective cohort study using electronic health records from TriNetX included individuals age 18 years or older with various lengths of continuous GLP-1 use between September 2014 and November 2023. Applying an intention-to-treat framework, we used linear mixed effects models and propensity score adjustment to model changes in BMI after GLP-1 discontinuation while accounting for correlated within-person observations and potential confounders.

Results

A total of 78,076 (19.7%) individuals used GLP-1s continuously for 3 months, 23,861 (6.0%) for 6 months, and 12,642 (3.2%) for 9 months. The median BMI prior to initiation was 36.38 (IQR 36.30–36.46), which declined by 2.15% (IQR 2.10%–2.21%) to 35.81 (IQR 35.7–35.92) among individuals with 3 months of continuous GLP-1 use. Median BMI declines were greater among individuals with 6 months (4.38%, IQR 4.27%–4.48%) and 9 months (5.56%, IQR 5.34%–5.78%) of continuous use. On average, weight loss among discontinuers at months 3, 6, and 9 slowed in comparison to their counterparts.

Conclusions

Among this real-world sample, GLP-1 use was associated with more modest weight loss than has been demonstrated in randomized controlled trials.

Objective

We aimed to compare the effectiveness and safety of semaglutide 1.0 mg versus dulaglutide 1.5 mg and liraglutide 1.8 mg in patients with type 2 diabetes mellitus (T2DM) under routine clinical care.

Methods

This multicenter, retrospective, real-world study enrolled Chinese adults with T2DM who initiated GLP-1 receptor agonist therapy in endocrinology clinics between January 1, 2022, and August 31, 2024. We compared the effectiveness of these agents on HbA1c and weight loss, with safety as a key exploratory endpoint. Additionally, the UK Prospective Diabetes Study Outcomes Model 2.1 was utilized to project long-term health outcomes.

Results

This multicenter retrospective study included 111, 74, and 107 patients treated with semaglutide 1.0 mg, dulaglutide 1.5 mg, and liraglutide 1.8 mg, respectively. After 1:1 propensity score matching, semaglutide demonstrated significantly greater HbA1c reduction compared to both dulaglutide (−0.27% ± 0.70%, p = 0.008) and liraglutide (−0.39% ± 0.87%, p < 0.001), along with higher glycemic target achievement rates. Semaglutide was associated with improved outcomes in all death, cardiovascular death, and other death endpoints. No significant differences in safety profiles were observed among the three treatment groups.

Conclusions

Semaglutide demonstrated superior glycemic control and weight loss compared to both dulaglutide and liraglutide, whereas dulaglutide and liraglutide exhibited comparable clinical efficacy.

Objective

This study examined the impact of a 2-week eucaloric diet high in ultraprocessed foods (UPF) compared to a diet without UPF (non-UPF) on ad libitum energy intake (EI) and food selection in individuals aged 18–25.

Methods

In a randomized, crossover, proof-of-concept trial, participants completed two 14-day controlled feeding periods (81% UPF vs. 0% UPF), with a 4-week washout. Diets were matched for macronutrients, fiber, added sugar, diet quality, and energy density. Following each condition, participants consumed an ad libitum buffet meal including UPF and non-UPF. Energy and food grams consumed were quantified. Statistical analyses were conducted for the full sample, late adolescents (aged 18–21), and young adults (aged 22–25).

Results

Twenty-seven individuals aged 22 ± 2 years (mean BMI = 24 ± 3 kg/m²) were included. Diet compliance was ~99% overall. There was no effect of diet condition on meal total kcal or grams consumed or UPF or non-UPF consumption in the full sample (all p > 0.05). In the exploratory age subgroup analysis, an interaction between diet and age was observed for total EI (p < 0.001), where total EI increased among adolescents following the UPF diet (p = 0.03, d = 0.79), but not in young adults.

Conclusions

Late adolescents may be susceptible to increased EI following a UPF diet. Future trials are warranted to evaluate this possibility.

Trial Registration: ClinicalTrials.gov: NCT05550818.

Objective

This cross-sectional study examined a Lifestyle Risk Factor Index (LSRI) in relation to adiposity measures including visceral adipose tissue (VAT) in the German National Cohort (NAKO).

Methods

Based on self-reports at baseline among 30,920 of > 205,000 NAKO eligible participants with magnetic resonance imaging (MRI) scans, one point each for not smoking, adhering to ≥ 3/7 diet recommendations, consuming ≤ 1 (women)/≤ 2 (men) alcoholic drinks/day, and ≥ 150 min/week physical activity was assigned. VAT volume, obtained from whole-body MRI at 3T, was analyzed by deep learning-based image segmentation. General linear models estimated adjusted geometric mean adiposity measures by LSRI and stratified analyses by sex and BMI.

Results

Of 18,508 participants aged 48.2 ± 12.2 years, the respective proportions for 0/1, 2, 3, and 4 LSRI points were 7%, 24%, 51%, and 18%. Participants with LSRI scores of 4 versus 0/1 had lower adjusted geometric mean volumes of VAT (2.3; 95% CI 2.2, 2.3 vs. 3.0; 95% CI 2.9, 3.1 L). These differences were slightly attenuated after adding BMI. This association was weaker for individuals with obesity than normal/overweight.

Conclusion

A combination of lifestyle factors appears to be associated with lower VAT volume, but an elevated BMI may have a greater influence on VAT accumulation than lifestyle behaviors alone.

Objective

This study examined the association between obesity severity and cardiometabolic and renal disease, using BMI as a surrogate for obesity severity.

Methods

This is a cross-sectional study using data from the United States Behavioral Risk Factor Surveillance System (BRFSS), 2011–2023. Survey-weighted logistic regression estimated odds ratios (OR) for the diagnosis of diabetes, hypertension, hyperlipidemia, kidney disease, myocardial infarction, stroke, and coronary artery disease among increasing BMI categories.

Results

Higher BMI was associated with increased odds of all conditions. For BMI ≥ 50 kg/m², odds were notably elevated for diabetes (OR 8.32; 95% CI: 7.78–8.91), hypertension (OR 6.07; 95% CI: 5.58–6.61), and kidney disease (OR 3.60; 95% CI: 3.21–4.03). The odds of cardiovascular disease also rose substantially, including myocardial infarction (OR 2.89; 95% CI: 2.56–3.28) and coronary artery disease (OR 3.44; 95% CI: 3.08–3.84). Mean age at diabetes diagnosis decreased with increasing BMI, from 52.2 years in Class I to 45.3 years in Class IV obesity.

Conclusions

Obesity severity is incrementally associated with cardiometabolic and renal disease burden, particularly among adults with BMI ≥ 50 kg/m². These findings highlight the urgent need for early, aggressive interventions targeting individuals with all classes of obesity.

Objective

Self-directed dietary restraint (i.e., outside of evidence-based weight management programs) has been associated with disordered eating in youth. This study examined associations between maladaptive facets of dietary restraint and disordered eating among youth with higher weight.

Methods

Participants (N = 529; mean age = 10.8 ± 2.08; BMI ≥ 85th percentile) self-reported dietary restraint (restraint over eating, avoidance of eating, food avoidance, desire for an empty stomach, and dietary rules) and disordered eating behaviors (i.e., objective and subjective binge eating, driven exercise, and vomiting) over the past 3 months. Network analysis estimated partial correlations between restraint factors and disordered eating behaviors.

Results

The restraint item most strongly associated with disordered eating behaviors was “dietary rules,” which was associated with “driven exercise” and “subjective binge eating.” The disordered eating behavior most strongly connected to restraint was “subjective binge eating,” which was positively associated with “dietary rules,” “desire for an empty stomach,” and “food avoidance.”

Conclusions

Trying to follow definite dietary rules may be associated with disordered eating behaviors in youth with higher weight. Prospective research is needed to examine causality among youth undergoing weight management interventions, which could inform screening and monitoring of restraint prior to and during weight management.

Objective

Most studies have investigated how childhood BMI impacts risks of single diseases. We investigated whether sex-specific patterns of disease diagnoses from ages 15 to 60 years differed by childhood BMI.

Methods

We included 112,952 children (55,603 girls) from the Copenhagen School Health Records Register, born 1962–1996, with measured weights and heights. BMI at 7 years was classified as underweight (4.3%), normal weight (83.1%), overweight (9.2%), or obesity (3.5%). Hospital-based diagnoses came from national registers. Sex-specific cumulative incidences were calculated for the 50 most frequent diseases per BMI group.

Results

Individuals with childhood obesity had the highest estimated mean number of hospital-based diagnoses by age 60, 18.2 (95% CI: 16.9–19.5) in females and 15.1 (13.8–16.4) in males. Corresponding estimates for normal weight were 14.7 (14.5–14.9) in females and 11.7 (11.5–11.8) in males. Among females and males with obesity in childhood, the most common diagnosis before age 60 years was adult overweight/obesity (36.4% and 11.8%, respectively). There were only minor differences for other diseases by childhood BMI categories.

Conclusions

Adults with obesity in childhood had the highest number of hospital-based diagnoses. Disease patterns across the life course were generally similar by childhood BMI groups apart from adult overweight and obesity.