Non-alcoholic fatty liver disease (NAFLD) is associated with overweight/obesity, metabolic syndrome and type 2 diabetes (T2D) due to chronic caloric excess and physical inactivity. Previous meta-analyses have confirmed associations between ultra-processed food (UPF) intake and obesity and T2D. We aim to ascertain the contribution of UPF consumption to the risk of developing NAFLD. We performed a systematic review and meta-analysis (PROSPERO (CRD42022368763)). All records registered on Ovid Medline and Web of Science were searched from inception until December 2022. Studies that assessed UPF consumption in adults, determined according to the NOVA food classification system, and that reported NAFLD determined by surrogate (steatosis) scores, imaging or liver biopsy were included. The association between UPF consumption and NAFLD was assessed using random-effects meta-analysis methods. Study quality was assessed, and evidence credibility evaluated, using the Newcastle Ottawa Scale and NutriGrade systems, respectively. A total of 5454 records were screened, and 112 records underwent full text review. From these, 9 studies (3 cross-sectional, 3 case-control and 3 cohort), analysing 60,961 individuals, were included in the current review. Both moderate (vs. low) (pooled relative risk 1.03 (1.00–1.07) (p = 0.04) (I² = 0%)) and high (vs. low) (1.42 (1.16–1.75) (<0.01) (I² = 89%)) intake of UPF significantly increased the risk of NAFLD. Funnel plots demonstrate low risk of publication bias. Consumption of UPF is associated with NAFLD with a dose–response effect. Public health measures to reduce overconsumption of UPF are imperative to reduce the burden of NAFLD, and the related conditions, obesity and T2D.

Background and aims: Poor cardiometabolic health is associated with dementia. Considering previous meta-analyses have confirmed associations between ultra-processed foods (UPFs) and cardiometabolic disease, we were interested in the contribution of UPF consumption to the risk of developing dementia. Methods: We performed a systematic review and meta-analysis of all records registered on Ovid Medline and Web of Science from inception until December 2022 [PROSPERO (CRD42023388363)]. Studies that assessed UPF consumption in adults, determined according to NOVA, and that reported dementia (Alzheimer’s disease, vascular dementia and mild cognitive impairment) determined by clearly stated diagnostic criteria (including formal assessment of dementia or use of diagnostic codes) were included. The association between UPF consumption and dementia was assessed using random-effects meta-analysis, controlling for confounding variables. Study quality was assessed using the Newcastle Ottawa Scale and evidence credibility evaluated using the NutriGrade system. Results: Seven thousand ten records were screened, and 122 records underwent full text review. From these, 10 observational (8 longitudinal) studies, analysing 867,316 individuals, were included. Included studies adjusted for age, socioeconomic status and co-morbidity, alongside other confounders. High (vs. low) intake of UPF was associated with increased risk of dementia (pooled relative risk 1.44 (95% confidence interval 1.09–1.90) (p = 0.02)) (I² = 97.0%), although moderate (vs. low) intake of UPF was not (1.12 (0.96–1.31) (0.13)) (85.0%). Funnel plots demonstrate low risk of publication bias. Conclusion: High UPF consumption is associated with dementia. Public health measures to reduce overconsumption of UPFs are imperative to reduce the burden of dementia. Graphical

The prevalence of obesity in older adults (people aged >60 years) is increasing in line with the demographic shift in global populations. Despite knowledge of obesity-related complications in younger adults (increased risk of type 2 diabetes, liver and cardiovascular disease and malignancy), these considerations may be outweighed, in older adults, by concerns regarding weight-loss induced reduction in skeletal muscle and bone mass, and the awareness of the ‘obesity paradox’. Obesity in the elderly contributes to various obesity-related complications from cardiometabolic disease and cancer, to functional decline, worsening cognition, and quality of life, that will have already suffered an age-related decline. Lifestyle interventions remain the cornerstone of obesity management in older adults, with emphasis on resistance training for muscle strength and bone mineral density preservation. However, in older adults with obesity refractory to lifestyle strategies, pharmacotherapy, using anti-obesity medicines (AOMs), can be a useful adjunct. Recent evidence suggests that intentional weight loss in older adults with overweight and obesity is effective and safe, hence a diminishing reluctance to use AOMs in this more vulnerable population. Despite nine AOMs being currently approved for the treatment of obesity, limited clinical trial evidence in older adults predominantly focuses on incretin therapy with glucagon-like peptide-1 receptor agonists (liraglutide, semaglutide, and tirzepatide). AOMs enhance weight loss and reduce cardiometabolic events, while maintaining muscle mass. Future randomised controlled trials should specifically evaluate the effectiveness of novel AOMs for long-term weight management in older adults with obesity, carefully considering the impact on body composition and functional ability, as well as health economics.

Background Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are treatments for type 2 diabetes (T2D). Beyond glucose-lowering and cardiorenal protection, these drugs may protect against pneumonia and sepsis. Aims This study assesses the impact of SGLT2i and GLP-1 RAs on the risk of incident pneumonia and severe sepsis. Methods A retrospective cohort study was conducted using anonymised electronic medical records from TriNetX, a global federated database. Two intention-to-treat analyses were performed, each with two cohorts of adult T2D patients. The first analysis compared individuals prescribed SGLT2i, and the second individuals prescribed GLP-1 RAs, with those prescribed dipeptidyl peptidase-4 inhibitors (DPP-4i). An active comparator new user design was used, with outcomes defined as time-to-incident pneumonia and severe sepsis. Propensity score matching (1:1) was applied to control for potential confounders, and patients were followed for 12 months. Secondary analyses compared SGLT2i and GLP-1 RAs against other glucose-lowering therapies. Results After propensity score matching, 352 687 patients were included in the SGLT2i versus DPP-4i comparison. SGLT2i treatment was associated with a risk reduction in incident pneumonia (HR 0.75 (95% CI 0.73, 0.78)) and severe sepsis (0.75 (0.73, 0.77)). In the GLP-1 RA versus DPP-4i comparison, 331 863 patients were included. GLP-1 RA treatment was associated with a risk reduction in incident pneumonia (0.60 (0.58, 0.62)) and severe sepsis (0.61 (0.59, 0.63)). Conclusion SGLT2i and GLP-1 RAs are associated with a reduced risk of incident pneumonia and severe sepsis in patients with T2D. Further research and focused randomised controlled trials are warranted to explore the broader clinical implications of these treatments.

Background Polycystic ovary syndrome (PCOS) is associated with adverse clinical outcomes that may differ according to PCOS phenotype. Methods Using UK Biobank data, we compared the incidence of type 2 diabetes (T2D), metabolic dysfunction associated steatotic liver disease, cardiovascular disease (CVD), hormone-dependent cancers, and dementia between PCOS participants and age- and body mass index-matched controls. We also compared multiorgan (liver, cardiac, and brain) magnetic resonance imaging (MRI) data and examined the impact of PCOS phenotype (hyperandrogenic and normoandrogenic) on these outcomes. Results We included 1008 women with PCOS (defined by diagnostic codes, self-reported diagnoses, or clinical/biochemical features of hyperandrogenism and a/oligoCmenorrhoea) and 5017 matched controls (5:1 ratio); median age, 61 years, body mass index, 28.4 kg/m². Adjusted Cox proportional hazard modeling demonstrated PCOS participants had greater incident T2D [hazard ratio (HR) 1.47; 95% confidence interval (CI), 1.11-1.95] and all-cause CVD (1.76; 1.35-2.30). No between-group differences existed for cancers or dementia. Liver MRI confirmed more PCOS participants had hepatic steatosis (proton density fat fraction >5.5%: 35.9 vs 23.9%; P = .02) and higher fibroinflammation (corrected T1 721.4 vs 701.5 ms; P = <.01) vs controls. No between-group difference existed for cardiac (biventricular/atrial structure and function) or brain (grey and white matter volumes) imaging. Normoandrogenic (but not hyperandrogenic) PCOS participants had greater incident all-cause CVD (1.82; 1.29-2.56) while hyperandrogenic (but not normoandrogenic) PCOS participants were more likely to have hepatic steatosis (8.96 vs 6.04 vs 5.23%; P = .03) with greater fibroinflammation (776.3 vs 707.7 vs 701.9 ms; P=<.01). Conclusion Cardiometabolic disease may be increased in PCOS patients with a disease phenotype-specific pattern.

Rationale: Glucagon-like peptide-1 (GLP-1) receptor agonists (liraglutide, semaglutide) and dual glucose-dependent insulinotropic polypeptide (GLP-1/GIP) receptor agonists (tirzepatide) are approved for treatment of type 2 diabetes (T2D) and obesity. Objective: To compare the relative efficacy of tirzepatide, liraglutide, and semaglutide in reducing major adverse cardiovascular events (MACEs) in patients with obstructive sleep apnea (OSA) and T2D. Methods: We performed a retrospective cohort analysis in a large global federated database of patients with OSA and T2D. Two cohorts were generated, both with a treatment arm of patients prescribed tirzepatide. Liraglutide and semaglutide-treated patients provided the reference arms in cohort 1 and cohort 2, respectively. Cohorts underwent propensity-score matching at a 1:1 ratio for confounders. We examined rates of incident MACEs (composite outcome and individual components) over an 18-month follow up, and performed stratified analyses by body mass index, age, sex, and ethnicity. Finally, we assessed incident OSA in a secondary analysis of patients with T2D treated with tirzepatide compared with liraglutide and semaglutide. Results: After matching, each treatment arm included 7,836 patients in cohort 1 and 7,394 patients in cohort 2. Tirzepatide reduced the risk of incident MACEs compared with liraglutide (hazard ratio, 0.58; 95% confidence interval, 0.51–0.66) and semaglutide (0.86; 0.74–0.99). Tirzepatide was more efficacious in younger, male patients of White ethnicity. Moreover, tirzepatide reduced incident OSA compared with liraglutide (0.89; 0.82–0.97) but not semaglutide (0.94; 0.86–1.02). Conclusions: In patients with OSA and T2D, tirzepatide is associated with a lower incidence of MACEs compared with liraglutide and semaglutide. More robust randomized, controlled evidence is needed for these drugs in patients who are at such high risk.