Obesity最新文献

Objective

This study aimed to characterize the reasons for treatment discontinuation with injectable semaglutide or tirzepatide for obesity in regular clinical practice.

Methods

This cross-sectional study used electronic health record data between January 2022 and December 2024 from a single integrated health system in Ohio and Florida. The primary reason for treatment discontinuation was examined in a randomly selected sample of adults with overweight or obesity and without type 2 diabetes who initiated injectable semaglutide or tirzepatide and discontinued treatment within the first year.

Results

We randomly selected 288 patients; 145 received semaglutide and 143 tirzepatide. Overall, 137 patients (47.6%) discontinued their medication due to cost or insurance-related issues, 42 (14.6%) due to inability to tolerate the side effects, 34 (11.8%) as they were unable to fill the medication due to shortages, 7 (2.4%) as they switched to a compounded medication, and 5 (1.7%) due to unsatisfactory weight loss; 31 (10.8%) discontinued for other reasons, and for 32 (11.1%) patients the discontinuation reason was not specified in the electronic health record.

Conclusions

High cost or insurance-related issues are the most common reasons for treatment discontinuation with semaglutide or tirzepatide for obesity. Our findings highlight the need for policies to address cost and could inform discussions between healthcare providers and patients concerning cost and side effects.

Objective

Fatty acids in adipose tissue are key structural and metabolic regulators of cardiometabolic health, but the genetic architecture governing depot-specific composition in subcutaneous (SAT) and visceral adipose tissue (VAT) is not well defined.

Methods

We used MRI-derived estimates of fatty acid composition in SAT and VAT from 33,583 UK Biobank participants to perform genome-wide association studies. Functional annotation, fine mapping, colocalization, and expression QTL analyses were conducted to prioritize likely causal variants and explore mechanisms.

Results

We identified six loci associated with adipose tissue fatty acid composition, including both shared (PKD2L1, INSIG1) and depot-specific associations (LEKR1 and KLF14 for SAT; CDCA2 for VAT). The strongest association, rs603424-G (near PKD2L1), was linked to higher monounsaturated and polyunsaturated fatty acids, lower saturated fatty acids, and increased SCD1 expression in SAT and VAT, suggesting a role in desaturation and lipid remodeling. Several loci were linked to cardiometabolic outcomes including type 2 diabetes, hypertension, and cholelithiasis, with functional evidence supporting gene–diet interactions at the PKD2L1 locus.

Conclusions

Our findings uncover genetic determinants of human adipose tissue fatty acid composition, highlight depot-specific regulation, and point to SCD1 as a potential metabolic regulator. These results deepen understanding of lipid metabolism and its links to cardiometabolic risk.

Objective

This study compared the effects of a very low-energy diet (VLED), alone or combined with sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB), on glucose-dependent insulinotropic polypeptide (GIP) and glucagon concentrations, hormones likely to play a role in weight loss maintenance.

Methods

Participants with severe obesity underwent 10 weeks of VLED alone (n = 15) or combined with SG (n = 15) or RYGB (n = 14). Plasma concentrations of glucagon and GIP (fasting and the first 60 min of a meal), insulin sensitivity, respiratory quotient, and resting energy expenditure (REE) were measured at pre- and post-intervention. Differences in hormone concentrations between groups at follow-up and associations between hormones and metabolic outcomes were evaluated.

Results

Fasting glucagon concentrations were higher, while postprandial GIP concentrations were lower, after RYGB compared to SG. An increase in postprandial glucagon was associated with a decrease in Matsuda index in the RYGB group and with an increase in REE in all groups. An increase in fasting GIP was correlated with an increase in HOMA-IR.

Conclusions

RYGB was associated with lower postprandial GIP and greater glucagon concentrations compared with other groups. These hormonal changes are likely to impact REE, as well as insulin sensitivity, potentially modulating the likelihood of weight loss maintenance.

Trial Registration: ClinicalTrials.gov identifier NCT04051190.

Objective

This study aimed to examine the association of BMI with cognitive performance in individuals with diabetes or prediabetes.

Methods

Among Diabetes Prevention Program Outcomes Study (DPPOS) participants, BMI was categorized as normal (< 25 kg/m²), overweight (25 to < 30 kg/m²), or obesity (≥ 30 kg/m²). Cognitive tests included the Brief Spanish English Verbal Learning Test (B-SEVLT) and the Digit Symbol Substitution test (DSST). The relationship between BMI at DPPOS Year 8 (Y8) visit and cognitive test scores at Y8, Y10, and Y15 visits was ascertained via linear mixed models accounting for repeated measures. Analogous models related BMI to Modified Mini-Mental State exam (3MS) score at Y15.

Results

A total of 2285 participants (mean ± SD age 51.1 ± 10.0 years; 67.7% female; 31% with overweight; and 60% with obesity at DPPOS Y8) completed cognitive assessments. Those with overweight or obesity at Y8 had a slower decline in B-SEVLT immediate and delayed recall, compared with those with normal BMI; 3MS performance was higher among individuals with overweight or obesity compared to those with normal BMI at Y15.

Conclusions

Among individuals with prediabetes or diabetes in DPPOS, overweight or obesity was associated with slower decline in verbal learning and memory compared with those with normal BMI.

Objective

This study aimed to investigate the associations of body roundness index (BRI) with cardiometabolic disease (CMD), cardiometabolic multimorbidity (CMM), and all-cause mortality, while evaluating its impact across different stages of CMM progression.

Methods

In this prospective cohort study, 87,902 participants from the Kailuan cohort were categorized into BRI quartiles. Cox models estimated hazard ratios (HRs) and 95% CIs for the first occurrence of cardiometabolic disease (FCMD), CMM, and mortality. Multistate models assessed BRI's role across CMM progression.

Results

Over a median follow-up of 13.68 years, 21,636 participants developed FCMD, 2114 developed CMM, and 14,782 died. Elevated BRI increased risks of FCMD, CMM, and mortality in Cox models. Multistate analysis revealed differential BRI effects across CMM progression: participants in the highest versus lowest BRI quartile showed HRs of 2.08 (1.99–2.17) for healthy-to-FCMD transition, 1.61 (1.38–1.88) for FCMD-to-CMM transition, and 1.09 (1.03–1.16), 0.99 (0.89–1.10), and 0.73 (0.54–0.99) for mortality from the healthy state, FCMD, and CMM, respectively. BRI's impact varied by disease type (diabetes mellitus, myocardial infarction, stroke) and sex, with stronger associations in females.

Conclusions

Our findings emphasize dynamic BRI monitoring as a biomarker for early CMM risk identification and prognostic assessment, necessitating disease- and sex-specific prevention strategies.

Objective

Access to only high-fat diet (HFD) during the light versus dark cycle promotes different metabolic outcomes. We assessed changes in body weight/composition, feeding behavior, and metabolic parameters in mice fed HFD during the light or dark cycle with concomitant ad libitum access to chow.

Methods

Male C57BL/6J mice were housed in metabolic chambers with two hoppers containing chow. HFD was then provided in one hopper, with access restricted to the light or dark cycle. The other hopper provided ad libitum access to chow. Food intake, meal patterns, energy expenditure, activity, and substrate oxidation were measured for ~4 weeks. Body weight/composition was measured before and after ~4-week HFD access.

Results

Light cycle HFD access promoted greater weight and fat mass gain. Although daily caloric intake was equivalent between groups, light cycle HFD access increased preference for HFD and intake of larger, more frequent HFD meals during the daytime. Dark cycle HFD access promoted preference for chow and consumption of larger, more frequent chow meals.

Conclusions

Light cycle HFD access parallels detrimental metabolic outcomes of ad libitum HFD access. Dark cycle HFD access reduces weight gain and adiposity; this is associated with enhanced chow preference.

Objective

This study aimed to evaluate associations of maternal prepregnancy BMI with offspring BMI and blood pressure in childhood, specifically for infants born preterm.

Methods

In this observational cohort study of children in the Environmental Influences on Child Health Outcomes (ECHO) Cohort, we utilized four levels of maternal prepregnancy BMI and child BMI. Children were categorized as being born extremely, very, or moderately preterm; late preterm; or term.

Results

In total, 13,810 children from 44 ECHO cohorts were included in these analyses. After adjusting for maternal education, maternal age at delivery, and singleton birth, a monotonic dose relationship was noted between child BMI z-scores and maternal prepregnancy BMI level. For child blood pressure outcomes, only extremely preterm children born to mothers with healthy weight and obesity and very/moderately preterm children born to mothers with healthy weight had higher odds of elevated blood pressure/hypertension compared with their term counterparts.

Conclusions

High maternal prepregnancy BMI was associated with a stepwise increase in offspring BMI in childhood. Preterm children had a higher probability of elevated blood pressure/hypertension than term children. These findings highlight a possible window of opportunity to modify lifestyles and behavior of at-risk children prior to adolescence to positively impact adolescent cardiometabolic health.

Objective

This study aimed to evaluate the early effects of a comprehensive redevelopment of a low-income, minority community on adult obesity.

Methods

We analyzed longitudinal data on a cohort of public housing residents from Jordan Downs (JD), the community undergoing redevelopment, and a comparison group in Watts, Los Angeles, California. Difference-in-difference models with individual fixed effects were estimated on a sample of 421 adults comparing changes in BMI and waist circumference for JD versus comparison group residents between baseline (2018–2019) and follow-up (2021–2022). Quasi-experimental variation in redevelopment exposure was used to assess dose–response relationships. Secondary outcomes included diet and physical activity barriers and behaviors.

Results

There were no significant differences in BMI or waist circumference changes between JD residents (n = 279) and the comparison group (n = 149) overall. Within JD, those who moved to redeveloped areas (n = 75) experienced a 2.2% larger reduction in waist circumference (95% CI: −0.05 to −0.003) and a 10.6 percentage point (95% CI: −0.20 to −0.02) greater decline in abdominal obesity, relative to the comparison group. They reported greater declines in barriers to healthy eating and exercise, along with reduced added sugar intake, but no differential changes in BMI, obesity, physical activity, or diet quality.

Conclusions

Redeveloping low-income communities can reduce abdominal obesity.