Obesity and Its Comorbidities: Prevention and Therapy 2026

Obesity is ranked as one of the biggest health challenges facing humanity today. Globally, the number of obese people has almost tripled since 1975, and this lifestyle disease currently affects hundreds of millions of adults who suffer from major health problems due to it, such as heart disease, type 2 diabetes and some cancers, that weigh heavily on the global health systems, In order to keep high standards for methods, anthropometric variables, i.e., Height and Weight have been intentionally excluded from the features, because labels for obesity classes are based on these measurements; thus, including them would introduce target leakage. All models were individually tuned with Optuna (50 trials, TPE sampler), and the class imbalance was managed by the synthetic minority over-sampling technique (SMOTE), which was done only in training folds. The models were evaluated by stratified five-fold cross-validation, with the macro-averaged F1-score being used as the main metric for evaluation. The best model was the fine-tuned XGBoost, which gave a test macro F1-score value of 0.872 and a macro-AUC of 0.977. The model was higher performing than others such as Random Forest (F1 = 0.869), MLP (F1 = 0.777), and Logistic Regression (F1 = 0.605). This means that behavioral and lifestyle variables may have a very strong and sufficient signal to identify obesity status, even when there are no direct anthropometric measurements available. However, it is worth noting that results here represent only performance on a single public benchmark dataset, so they cannot be taken as proof that the model would do well in real-world clinical settings. With the advent of ML methods for obesity prediction, rigorous, leakage-free evaluation becomes indispensable. Apart from external validation of the clinical models on independent datasets, the use of interpretability tools such as SHapley Additive exPlanations (SHAP) and Local Interpretable Model-Agnostic Explanations (LIME) for understanding decision-making, as well as sex and gender subgroup analyses for evaluating fairness and equity, should also be pursued in the future. This study highlights the importance of rigorous, leakage-free evaluation in machine learning-based obesity research. Future work should focus on external validation using independent clinical cohorts, the integration of interpretability techniques such as SHapley Additive exPlanations (SHAP) and Local Interpretable Model-Agnostic Explanations (LIME), and subgroup analyses by sex and gender to assess model fairness and clinical equity. Full article

Background: Serum uric acid (SUA) has emerged as a relevant cardiometabolic and hepatic risk marker in adolescents with obesity. Cinnamon has shown metabolic benefits in adults; however, its effects on SUA and hepatic markers in pediatric populations remain unclear. This study aimed to evaluate the efficacy of cinnamon supplementation on serum uric acid, hepatic enzymes, and lipid profiles in adolescents with obesity. Methods: This is a secondary analysis of a randomized, double-blind, placebo-controlled clinical trial including 93 adolescents (10–18 years) with obesity (BMI ≥ 95th percentile). Participants received either 3 g/day of Cinnamomum verum or a placebo for 16 weeks, alongside lifestyle intervention. Changes in BMI z-score, SUA, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), and triglycerides were analyzed. Results: The cinnamon group showed a greater reduction in BMI z-score compared to placebo (Δ −0.08 vs. −0.02; p < 0.001). Serum uric acid decreased significantly in the cinnamon group (median change: −0.5 mg/dL [IQR: −1.0 to −0.2]) compared to placebo (−0.1 mg/dL [IQR: −0.4 to 0.2]; p < 0.01). Triglycerides also decreased in the cinnamon group (−18 mg/dL [IQR: −35 to −5]) versus placebo (−5 mg/dL [IQR: −20 to 10]; p < 0.05). Hepatic enzymes (ALT, AST, and GGT) decreased significantly within both groups, without significant differences between groups. In a subgroup of participants with elevated baseline ALT (n = 67), ALT decreased in both groups (placebo: 32.0 to 30.0 U/L, p = 0.004; cinnamon: 33.0 to 26.0 U/L, p = 0.001), with a greater but non-significant reduction in the cinnamon group (Δ −6.0 vs. −2.0 U/L; p = 0.197). Conclusions: Cinnamon supplementation significantly reduced serum uric acid and improved metabolic parameters in adolescents with obesity. These findings suggest that cinnamon may act as an adjunct strategy targeting early cardiometabolic risk markers, particularly uric acid. Full article

Background: Obesity is increasingly recognized as a complex condition characterized by the convergence of metabolic dysregulation and psychological vulnerability. Insulin resistance (IR) has been identified as a biological bridge linking metabolic imbalance with affective symptoms such as anxiety, depression, and disordered eating behaviors. Methods: Fifteen obese adults (mean age = 25 ± 4.3 years) were evaluated through clinical examination, anthropometric assessment (BMI), biochemical assays (fasting insulin, AST, ALT), and standardized psychological assessments (STAI, BDI-II). In parallel, a rapid systematic review (2019–2025) synthesized evidence on the association between IR, affective dysregulation, binge eating disorder (BED), and the clinical role of insulin-sensitizing or incretin-based therapies. Results: Participants exhibited marked hyperinsulinemia (M = 79 μU/mL, SD = 6.61) and elevated anxiety (STAI-Trait = 54.22 ± 22.4) and depression scores (BDI-II = 21.6 ± 7.5). Liver enzymes were within normal limits. Literature synthesis confirmed consistent associations between IR, mood symptoms, and BED, associated with biological processes including inflammation, HPA axis hyperactivity, and dopaminergic imbalance. Integrated treatment approaches combining cognitive-behavioral therapy, medical nutrition therapy, and insulin-sensitizing agents (metformin, GLP-1RA, and GLP-1/GIP RA) were supported as effective and safe options. Conclusions: The coexistence of insulin resistance and emotional dysregulation in obesity is consistent with the hypothesis of a bidirectional metabolic–emotional axis. Early, integrated interventions addressing both metabolic and psychological domains may improve clinical outcomes and reduce progression toward chronic metabolic and psychiatric comorbidity. Full article

Metabolic syndrome (MetS) is a multifactorial condition characterized by central obesity, hypertension, dyslipidaemia, and hyperglycaemia, predisposing individuals to cardiovascular disease and type 2 diabetes. This cross-sectional study investigated the relationship between dietary intake, sociodemographic factors, and components of MetS among Saudi adults aged 30 years and older attending King Abdulaziz University Hospital. Fifty-three participants meeting MetS diagnostic criteria were assessed through anthropometric measurements, biochemical markers, and two-day dietary recalls analyzed using MyFood24 software. Descriptive and correlation analyses were conducted using SPSS 26.0. The majority of participants (73.6%) were aged over 50 years, were obese (75.5%), and exhibited a high waist circumference (94.3%). Low fibre (6.6 g/day) and high fat (41.8 g/day) intake patterns were evident. Salt intake showed a significant inverse correlation with systolic blood pressure (ρ = −0.36, p < 0.01), potentially reflecting under-reporting or dietary adjustments following diagnosis. Higher BMI correlated positively with waist circumference and diastolic pressure, while frequent physical activity correlated negatively with these parameters. These findings emphasize the influence of diet and lifestyle on metabolic risk and underscore the need for culturally tailored interventions promoting balanced macronutrient intake, increased fibre consumption, and enhanced physical activity to mitigate MetS prevalence among Saudi adults. Full article

Obesity affects approximately 40% of U.S. adults and is associated with increased cardiometabolic risk. While lifestyle interventions remain fundamental, pharmacologic therapies such as Semaglutide and tirzepatide have demonstrated significant weight reduction in clinical trials when titrated to maintenance doses. However, real-world adherence to recommended titration schedules remains unclear. This retrospective observational study evaluated adults prescribed Semaglutide (Wegovy^®) or Tirzepatide (Zepbound^®) for weight management between January 2021 and April 2025 through ICUBAcares, a pharmacist-led call center. Primary outcomes included the proportion of patients reaching the recommended maintenance dose and time required to do so. Secondary outcomes examined prescriber specialty patterns and monthly plan costs for non-optimized dosing. Among 739 medication courses, 52.9% of Semaglutide users reached the 2.4 mg dose versus 77.6% of tirzepatide users reaching 15 mg (p < 0.001). Median time to maintenance was significantly shorter for tirzepatide (32 days) than Semaglutide (143 days) (p < 0.001). Endocrinologists had the highest success rate for Tirzepatide (88.2%), while family medicine had the highest volume for both. Non-optimized dosing was associated with higher estimated monthly plan costs. These findings underscore the importance of improving adherence to titration protocols in real-world settings to maximize both clinical and economic outcomes in obesity pharmacotherapy. Full article