Obesity (Silver Spring, Md.)最新文献

Objective: The high cost of novel glucagon-like peptide-1 receptor agonist (GLP-1 RA) class agents often limits access and creates barriers to care. This real-world study evaluated the efficacy of older-generation generic antiobesity medications (AOMs) for weight maintenance after 1 year of GLP-1 RA therapy in patients who had achieved successful weight loss.

Methods: We prospectively followed patients (N = 105) who had completed 12 months of therapy and were part of a "medical weight loss bundle," which included 12 months of GLP-1 RA therapy followed by 6 months of transition care. The baseline mean BMI was 36.4 kg/m². Body weight outcomes were measured at 6, 12, 18, and 24 months.

Results: After the medical weight loss bundle, 40 patients transitioned to generic AOMs. At 12 months, this cohort lost an average of 18.3%, 95% CI [13.0%, 23.6%] body weight from baseline, with a mean BMI of 27.9 kg/m². At 18 months, they maintained the weight loss, with a mean BMI of 27.9 kg/m². Subsequent follow-up visits (average 1.5 months later) without GLP-1 RAs showed further reduction, resulting in a total average weight loss of 25.5%, 95% CI [23.1%, 27.9%] compared to the initial visit.

Conclusions: Patients successfully treated with GLP-1 RAs can maintain their weight loss using generic older-generation AOMs, suggesting potential cost savings for insurers and implications for policy regarding AOM coverage.

Objective: The objective of this study was to identify sex differences in ntrahepatocellular (HCL) and intramyocardial lipids (MYCL) and cardiac function in participants with different grades of glucometabolic impairment and different BMI strata.

Methods: Data from 503 individuals from 17 clinical experimental studies were analyzed. HCL and MYCL were assessed with 3T and 7T scanners by magnetic resonance spectroscopy. Cardiac function was measured with a 3T scanner using electrocardiogram-gated TrueFISP sequences. Participants were classified as having normoglycemia, prediabetes, or type 2 diabetes. Three-way ANCOVA with post hoc simple effects analyses was used for statistical assessment.

Results: Consistent increases of HCL with BMI and deterioration of glucose metabolism, especially in female individuals, were detected. MYCL increased with BMI and glucose impairment in female individuals, but not in male individuals. Sex differences were found in cardiac function loss, with significant effects found among male individuals with worsening glucose metabolism. Myocardial mass and volume of the ventricle were higher in male individuals in all groups. This sex difference narrowed with increasing BMI and with progressing dysglycemia.

Conclusions: Sex differences in HCL and MYCL may be associated with a higher cardiovascular disease risk observed in female individuals progressing to diabetes. Further studies are needed to elucidate possible sex differences with advancing glucometabolic impairment and obesity and their potential impact on cardiovascular outcomes.

Objective: Apolipoprotein A4 (APOA4) is synthesized by the small intestine in response to dietary lipids. Chronic exposure to a high-fat diet (HFD) desensitizes lipid-induced APOA4 production and attenuates brown adipose tissue (BAT) thermogenesis. We hypothesized that exogenous APOA4 could increase BAT thermogenesis and energy expenditure in HFD-fed mice, resulting in decreased obesity and improved glucose tolerance.

Methods: BAT and inguinal white adipose tissue (IWAT) thermogenesis, body composition, energy intake and expenditure, and locomotor activity were measured using an infrared camera, immunoblots, quantitative magnetic resonance imaging, and a comprehensive lab animal monitoring system. An intraperitoneal glucose tolerance test and hepatic lipid accumulation and steatosis were assayed.

Results: Mice receiving continuous infusion of APOA4 for the last 4 weeks of 10 weeks of HFD feeding gained no additional body weight and had reduced fat mass but enhanced BAT and IWAT thermogenesis and energy expenditure, despite unaltered food intake and locomotor activity. Additionally, APOA4 infusion elevated fatty acid β oxidation; decreased lipogenesis, lipid accumulation, and steatosis in liver; and improved glucose tolerance.

Conclusions: Maintenance of plasma APOA4 via exogenous APOA4 protein parallels elevation of BAT and IWAT thermogenesis, hepatic fatty acid β oxidation, and overall energy expenditure, with subsequent prevention of additional weight gain in HFD-fed obese mice.

Objective: Previous studies have investigated the association between hepatic fat and intrapancreatic fat deposition (IPFD); however, results have been inconclusive. The presence of cardiometabolic factors in certain subpopulations could explain this discrepancy. The aim of the present study was to use moderation analyses to determine the conditions under which hepatic fat is associated with IPFD.

Methods: All participants underwent 3T abdominal magnetic resonance imaging (MRI) and spectroscopy. Hepatic fat and IPFD were manually quantified by independent raters. Moderation analyses were performed with adjustment for sex and ethnicity.

Results: There were 367 participants included. Adjusted analyses of the overall cohort revealed that age, glycated hemoglobin (HbA_1c), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides were significant moderators (p < 0.05) of the association between hepatic fat and IPFD. Ranges of significance included age < 61 years, HbA_1c < 45 mmol/mol, LDL-C < 157 mg/dL, HDL-C > 36 mg/dL, and triglycerides < 203 mg/dL.

Conclusions: The association between hepatic fat and IPFD is generally present in young and middle-aged adults with good cardiometabolic health, whereas the link between the two fat depots becomes uncoupled in older adults or individuals with cardiometabolic risk factors.

Objective: This study investigated how obesity, BMI ≥ 30 kg/m², abdominal adiposity, and systemic inflammation relate to neuroinflammation using diffusion basis spectrum imaging.

Methods: We analyzed data from 98 cognitively normal midlife participants (mean age: 49.4 [SD 6.2] years; 34 males [34.7%]; 56 with obesity [57.1%]). Participants underwent brain and abdominal magnetic resonance imaging (MRI), blood tests, and amyloid positron emission tomography (PET) imaging. Abdominal visceral and subcutaneous adipose tissue (VAT and SAT, respectively) was segmented, and Centiloids were calculated. Diffusion basis spectrum imaging parameter maps were created using an in-house script, and tract-based spatial statistics assessed white matter differences in high versus low BMI values, VAT, SAT, insulin resistance, systemic inflammation, and Centiloids, with age and sex as covariates.

Results: Obesity, high VAT, and high SAT were linked to lower axial diffusivity, reduced fiber fraction, and increased restricted fraction in white matter. Obesity was additionally associated with higher hindered fraction and lower fractional anisotropy. Also, individuals with high C-reactive protein showed lower axial diffusivity. Higher restricted fraction correlated with continuous BMI and SAT particularly in male individuals, whereas VAT effects were similar in male and female individuals.

Conclusions: The findings suggest that, at midlife, obesity and abdominal fat are associated with reduced brain axonal density and increased inflammation, with visceral fat playing a significant role in both sexes.

Objective: There is no clear evidence on the risk of gestational weight loss (GWL) for individuals with obesity. Our study aimed to assess the association between GWL and adverse perinatal outcomes among individuals with obesity.

Methods: This population-based retrospective cohort study examined individuals with prepregnancy BMI ≥ 30 kg/m² who had a singleton pregnancy, using Ontario, Canada, birth registry data from 2012 to 2020. The primary outcome was a composite of adverse outcomes, including perinatal death and neonatal morbidity. The association between GWL and risk of adverse perinatal outcomes was estimated using generalized estimating equation models and restricted cubic spline regression analysis. Stratified analysis was conducted by obesity class.

Results: Of the 157,205 individuals with obesity, 6.1% experienced GWL. Compared with adequate gestational weight gain, GWL was associated with an increased risk of a composite of adverse perinatal outcomes (adjusted risk ratio: 1.31; 95% CI: 1.22-1.39). Similar results were observed in the stratified analysis. Restricted cubic spline regression analysis revealed that average weekly gestational weight changes displayed a nonlinear U-shaped association, with a higher risk of a composite of adverse perinatal outcomes noted in the extremities, particularly toward GWL and excessive weight gain.

Conclusions: Our findings suggest that GWL may increase the risk of adverse perinatal outcomes across all obesity classes.