Search Results (339)

Metabolic syndrome (MetS) drives cardiac remodeling and fibrosis, contributing to diastolic dysfunction and heart failure with preserved ejection fraction, but chamber-specific mechanisms remain poorly defined. New Zealand White rabbits were fed a high-fat/high-sucrose diet for 28 weeks to induce experimental MetS. Systemic phenotype, cardiac structure (echocardiography), myocardial fibrosis (Picrosirius red histology), myosin/collagen gene expression (qRT-PCR), and chamber-specific proteomics were assessed across left/right atria and ventricles. The model reproduced central obesity, glucose intolerance, dyslipidemia, and mild hypertension, with concentric left ventricular hypertrophy and selective ventricular fibrosis, as follows: increased collagen in left ventricle (LV) and right ventricle (RV), unchanged in atria. Ventricular α-myosin heavy-chain gene expression was upregulated, while collagen I and α-smooth muscle actin transcripts showed ventricular-specific downregulation. Proteomics revealed atrial metabolic and cytoskeletal adaptations with minimal extracellular matrix involvement; ventricles displayed early profibrotic cues (galectin-3 in LV), metabolic inefficiency (impaired glycolysis/ATP production in LV; lipid oxidation shift in RV), and diminished provisional matrix support. Conclusions: concentric LV hypertrophy and great vessel enlargement occurred without systolic/diastolic dysfunction; ventricular-selective fibrosis, α-myosin heavy-chain upregulation, type I collagen/α-smooth muscle actin downregulation, and chamber-specific proteomic changes showed atrial adaptation versus ventricular early profibrotic/metabolic inefficiency. Full article

Multiple interacting risk factors can influence the origin of asthma. Asthma is characterized by different clinical phenotypes, each of which includes different endotypes. There are four main clinical asthma phenotypes: (1) early-onset mild allergic asthma; (2) early-onset allergic moderate-to-severe remodeled asthma; (3) late-onset non-allergic eosinophilic asthma; and (4) late-onset non-eosinophilic non-allergic asthma. The main endotypes of asthma are T-helper (Th)-2 low and Th-2 high. The identification of asthma endotypes might help precision-based care move toward the personalized management of airway inflammation. In this scenario, it is important to know how the risk factors affect the pathophysiology of asthma. Accordingly, we focus our attention on the impact of obesity and air pollutants and how these risk factors together with epigenetic alterations influence the asthma phenotype/endotype and the pathogenesis of airway diseases. Our aim is to disseminate the progress of studies in this area by reporting recent observations on the topic. Finally, we believe that data/observations enclosed in this review suggest the need of further epidemiological studies to be useful to examine simultaneously the effect of more than one risk factor on clinical and biologic parameters of asthma. Full article

Background and Objectives: The pathogenesis of liver steatosis is associated with obesity and systemic inflammation, particularly in subjects with body mass index (BMI) above 40 kg/m² and altered serum levels of tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10). Recent evidence suggests that disruption of the blood–brain barrier (BBB) may be associated with the development of steatosis, although limited data are available in humans. Thus, we assessed serum levels of neuron-specific enolase (NSE), transglutaminase 2 (TGM2), and glial fibrillary acidic protein (GFAP) as indirect markers of BBB dysfunction and examined their associations with steatosis severity, TNF-α and IL-10 in patients with morbid obesity. Materials and Methods: We biopsied the liver during bariatric surgery to assess steatosis by histology and serum markers by ELISA. Results: Most study subjects were women aged 38.7 ± 9.9 years with an average BMI of 42.3 ± 7.9 kg/m² and a steatosis prevalence of 78.9%. After grading steatosis as none (n = 8), mild (n = 17), moderate (n = 8), or severe (n = 5), we found no differences in sex, age, BMI, comorbidities, or laboratory variables, including liver enzymes. One-way ANOVA showed that serum IL-10 was 4-fold less in severe steatosis than in mild steatosis (p = 0.038), whereas TNF-α levels increased twice in severe steatosis compared to no steatosis (p = 0.029). NSE and GFAP serum levels, but not TGM2, increased proportionally to steatosis stage, showing differences between severe steatosis and no steatosis (p = 0.012 and p = 0.0002, respectively). Pearson correlation coefficients showed that NSE and GFAP were significantly associated with TNF-α (r = 0.600 and r = 0.402, respectively), but not with IL-10. Conclusions: Steatosis severity is significantly associated with markers of BBB disruption and systemic inflammation in patients with morbid obesity, suggesting a link between the BBB and liver steatosis. Full article

Introduction: This systematic review examines the association between ultraprocessed food (UPF) intake and cognitive and executive function in adults. Given the global rise in overweight and obesity and the increasing consumption of UPFs, understanding their potential impact on brain health is of growing importance. Method: A comprehensive literature search was conducted in PubMed, EBSCO, and Scopus databases following PRISMA guidelines. Fourteen studies met inclusion criteria, encompassing cross-sectional, longitudinal, and experimental designs. Risk of bias was assessed using the National Institutes of Health Quality Assessment Tool. Results: The majority of studies (78.5%) reported a significant association between higher UPF consumption and poorer cognitive outcomes, including deficits in memory, executive function, and global cognition. Longitudinal studies consistently demonstrated that increased UPF intake is linked to accelerated cognitive decline and a higher risk of mild cognitive impairment and dementia, particularly in middle-aged and older adults. In contrast, cross-sectional findings were more heterogeneous, and evidence in younger populations remains limited and inconclusive. Conclusions: Overall, the findings suggest that high UPF consumption may be a modifiable risk factor for cognitive decline. However, methodological variability and the predominance of observational studies highlight the need for further longitudinal and experimental research to clarify causal mechanisms. Full article

Background: Meralgia paresthetica is a neuropathic pain syndrome caused by compression of the lateral femoral cutaneous nerve (LFCN). While often self-limited, a subset of patients develops persistent symptoms requiring interventional management. Ultrasound guidance has improved accuracy and safety in peripheral nerve blocks, but evidence from Internal Medicine-led procedures remains limited. Methods: We performed a retrospective, observational case series including all patients aged ≥17 years who underwent ultrasound-guided LFCN blocks at Virgen del Rocío University Hospital between 2016 and 2024. Demographic data, comorbidities, procedural details, complications, and clinical outcomes were collected. Symptomatic response and recurrence were assessed descriptively. Results: Eleven patients were included (10 women; median age 56 years). The most frequent comorbidities were obesity (45.5%) and type 2 diabetes mellitus (18.2%). Clinical improvement following LFCN block was achieved in 10 of 11 patients (91%). Three patients (27%) experienced recurrence, with a median time to recurrence of 24 months; two underwent a second successful block, and one showed spontaneous resolution. No major complications occurred, and only one patient developed a mild, self-limited local reaction. Conclusions: Ultrasound-guided LFCN block is a safe, well-tolerated, and highly effective intervention for patients with persistent meralgia paresthetica. Outcomes achieved by an Internal Medicine specialist appear consistent with previously published reports from anesthesiology settings, underscoring the value of point-of-care ultrasound as a practical and precise tool for managing neuropathic pain within Internal Medicine settings. Full article

Obesity represents one of the most critical global public health challenges. Pancreatic lipase (PL) serves as a key therapeutic target for obesity control, whereas clinical synthetic PL inhibitors are greatly restricted by adverse reactions. Traditional Chinese medicines (TCMs) have a long-standing history in regulating lipid metabolism and ameliorating obesity-related disorders, and are characterized by remarkable structural diversity, low toxicity, and mild side effects, thus representing a promising source for developing safe and efficient PL inhibitors. In this work, an integrated strategy combining in silico screening and in vitro validation was employed to identify potential PL inhibitors from TCM components, including molecular docking, molecular dynamics simulation, MM/PBSA binding free energy computation, and in vitro enzymatic assay. Six compounds with docking scores ranging from −9.9 to −9.0 kcal/mol were selected for further investigation. Molecular dynamics simulations verified the favorable structural stability of the corresponding ligand–PL complexes, and MM/PBSA calculations demonstrated negative binding free energies from −21.24 ± 0.39 to −12.03 ± 0.40 kcal/mol. In vitro experiments indicated that three compounds (Hydroxygenkwanin, Atractylenolide I, and Peiminine) showed effective PL inhibitory activity, with IC₅₀ values of 0.128 ± 0.009, 0.584 ± 0.031, and 0.748 ± 0.042 mM, respectively. These values are comparable to quercetin (0.231 ± 0.034 mM) but significantly higher than orlistat (0.481 ± 0.023 μM), which is attributed to their non-covalent binding pattern. Collectively, this study validated the reliability of the integrated in silico and in vitro screening strategy, identified three effective pancreatic lipase inhibitors derived from TCMs, established a robust paradigm for the discovery of natural PL inhibitors, and laid a solid foundation for subsequent research on natural anti-obesity agents. Full article

The effects of chronic intermittent hypoxia associated with obstructive sleep apnea (OSA) on iron metabolism remain incompletely understood. This study aimed to evaluate whether serum hepcidin levels are associated with OSA severity independently of obesity and systemic inflammation. A total of 136 patients who underwent polysomnography for suspected OSA between April and December 2025 were included in the study. Participants were classified into control and OSA groups according to the Apnea–Hypopnea Index (AHI), and the OSA group was further categorized as mild, moderate, or severe. Demographic and anthropometric characteristics and Epworth Sleepiness Scale scores were recorded. Serum hepcidin levels were measured using an ELISA method and compared between groups, and their associations with clinical and polysomnographic parameters were analyzed. Serum hepcidin levels were significantly higher in patients with OSA than in the control group (48.83 ± 11.92 vs. 41.53 ± 12.43 ng/mL; p < 0.001) and increased progressively with disease severity. Hepcidin levels were not significantly correlated with conventional iron parameters but showed a strong positive association with the Oxygen Desaturation Index (ODI). In multivariable regression analysis, the positive relationship between AHI and serum hepcidin levels remained significant after adjustment for body mass index and C-reactive protein levels (p < 0.001). These findings suggest that elevated serum hepcidin levels in OSA are linked to hypoxic stress independently of obesity and systemic inflammation, indicating that hepcidin may represent a potential biomarker reflecting disease severity in OSA. Full article

Background and Objectives: During the past 25 years, a significant body of research has been conducted reporting on the salutary effects of the Mediterranean diet and extra-virgin olive oil, one of its main components. The initial studies were epidemiological observations on populations with very low mortality rates due to significant reductions in myocardial infarction fatalities. Population-based studies demonstrated that the Mediterranean diet with olive oil consumption is associated with a lower prevalence of cardiovascular and cerebrovascular disease, obesity, arthritis, and cancer. Materials and Methods: In this narrative review, we present recent studies on the effects of extra-virgin olive oil and the Mediterranean diet—compared with various other diets—on several vascular risk factors, including hypertension, hyperlipidemia, type 2 diabetes mellitus, and obesity, as well as their impact on cognitive decline and dementia. Results: This diet has been shown to improve cognitive function in patients with mild cognitive impairment, Alzheimer’s disease, vascular cognitive impairment, and vascular dementia. The main mechanisms responsible for cognitive improvement include control of arterial hypertension by reducing systolic and diastolic blood pressure, lowering triglycerides and low-density lipoprotein cholesterol and increasing high-density lipoprotein cholesterol, along with improvement in fasting glucose, insulin levels, and hemoglobin A1c in subjects with type 2 diabetes mellitus, as well as lowering body mass index and obesity. Conclusions: The Mediterranean diet and olive oil induce—along with prevention of cardiovascular disease and stroke—a significant improvement of vascular risk factors, slowing the progression of both vascular dementia and Alzheimer’s disease. There is a need for additional placebo-controlled clinical trials to confirm the supportive nutritional role of extra-virgin olive oil in age-associated cognitive decline in the elderly. Full article

Background: For decades, the ketogenic diet has been successfully used for the treatment of obesity, metabolic syndrome, and type 2 diabetes. The mechanisms through which it affects metabolism are not fully understood, but the hormonal changes that occur during ketogenic nutrition are likely to play an important role. Objectives: To investigate the effect of the ketogenic diet on various hormones associated with obesity and the accompanying metabolic disorders in childhood. Methods: One hundred children aged 8–18 years with obesity were enrolled. After baseline anthropometric, biochemical, and hormonal testing, they followed a 4-month “well-formulated ketogenic diet.” Fifty-eight of them successfully completed the study with follow-up assessments. Among them, 8 girls had polycystic ovary syndrome (PCOS) and 7 children had Hashimoto’s autoimmune thyroiditis. Results: At the end of the 4-month period, there was a significant decrease in basal insulinemia (p < 0.0001) and in mean morning cortisol levels (p = 0.04), as well as an increase in adiponectin levels (p = 0.04). All girls with PCOS experienced spontaneous menstrual cycles, accompanied by a reduction in testosterone levels. TSH levels showed no change for the whole group (p = 0.13), but there was a significant decrease in T3 (p < 0.0001) and a mild increase in T4 (p = 0.05). Among patients with Hashimoto’s thyroiditis, TSH levels were significantly higher at the end of the study. Conclusions: A short-term, well-formulated ketogenic diet in children with obesity is associated with hormonal changes that support weight loss and improve insulin sensitivity. The diet shows particularly beneficial effects in girls with PCOS and may be considered as part of a comprehensive therapeutic approach in these patients. Monitoring thyroid function during ketogenic nutrition is advisable in patients with hypothyroidism and thyroid disorders. Full article

Background: Obstructive sleep apnea (OSA) is a highly prevalent and heterogeneous disorder associated with substantial cardiometabolic morbidity. Although continuous positive airway pressure (CPAP) remains first-line therapy, long-term effectiveness is frequently limited by suboptimal adherence. Advances in airway devices, surgical techniques, neuromodulation, and pharmacologic therapies have expanded the therapeutic landscape and created opportunities for individualized, mechanism-based treatment. Methods: We conducted a selective, narrative review with structured quantitative synthesis of randomized controlled trials, comparative cohorts, long-term follow-up studies, registries, and mechanistic investigations addressing OSA therapies beyond CPAP. Evidence spanning oral appliances, upper-airway and skeletal surgery, hypoglossal nerve stimulation, neuromuscular electrical stimulation, positional therapy, and pharmacologic interventions targeting metabolic and non-anatomical endotypes was integrated. Outcomes of interest included apnea–hypopnea index (AHI), oxygenation, blood pressure, patient-reported symptoms, durability, safety, and real-world adherence. Results: Mandibular advancement devices (MADs) consistently reduced AHI relative to placebo and produced symptom relief comparable to CPAP in mild-to-moderate OSA, largely due to superior adherence. Palatal surgery yielded meaningful short-term improvement in selected patients but demonstrated limited long-term durability. In contrast, maxillomandibular advancement (MMA) achieved the largest and most durable reductions in OSA severity, with efficacy comparable to CPAP and superior to other surgical modalities in appropriate skeletal phenotypes. Hypoglossal nerve stimulation (HNS) produced substantial, durable improvements in AHI and symptoms with high adherence, supported by randomized trials, long-term follow-up, and real-world registry data; newer bilateral and proximal stimulation systems may further broaden candidacy. Neuromuscular electrical stimulation and positional therapy provided modest, phenotype-dependent benefits, primarily as adjunctive or early-stage interventions. A major advance is the emergence of metabolic and endotype-targeted pharmacotherapy: longitudinal data demonstrate a dose-dependent relationship between weight change and OSA progression or regression, while randomized trials show that GLP-1-based therapies—particularly dual GLP-1/GIP agonism with tirzepatide—produce large, clinically meaningful reductions in AHI and cardiometabolic risk in obesity-associated OSA. Additional pharmacologic strategies targeting ventilatory loop gain and arousal threshold further support an endotype-driven treatment paradigm. Conclusions: Contemporary OSA management is shifting from a CPAP-centric model toward a precision-guided, multimodal framework that aligns therapy with dominant anatomic and physiological contributors to airway collapse. Integrating metabolic, neuromodulatory, and structural interventions—often in combination—offers the potential for durable disease control and improved patient-centered outcomes. Future priorities include head-to-head and combination trials, long-term cardiovascular outcomes, cost-effectiveness analyses, and pragmatic tools to operationalize personalized OSA therapy in routine clinical practice. Full article

Background and Clinical Significance: Over the last two decades, glucagon-like peptide-1 (GLP-1) receptor agonists have dramatically improved the management of type 2 diabetes mellitus and obesity. Currently, little is known about the use of semaglutide (a second-generation GLP-1 receptor agonist) in patients with X chromosome abnormalities. Herein, we describe the therapeutic use of semaglutide in a woman with a partial deletion of the X chromosome long arm (partial Xq deletion) and comorbid obesity. We also conducted a narrative mini-review on overweight, obesity and common metabolic derangements in patients with partial Xq deletions and Turner syndrome. Case Presentation: A 65-year-old Italian woman with a partial Xq deletion, class 1 obesity, insulin resistance, prediabetes, hypercholesterolemia and metabolic dysfunction-associated steatotic liver disease (MASLD) was referred to our Institution for persistent difficulty in managing excess body weight despite regular adherence to different structured physical activity programs and hypocaloric diets. Therefore, we prescribed a combination therapy based on low-dose metformin (500 mg/day) and once-weekly subcutaneous semaglutide (as an adjunct to lifestyle intervention). At 5 months after initiation of the combination therapy, blood tests showed metabolic improvements, including improvement of prediabetes (0.3-percentage-point reduction in glycated hemoglobin [HbA1c] values) and normalization of markers of insulin sensitivity and insulin resistance (QUICKI, HOMA-IR and TyG index). At 8 months, the patient showed substantial weight loss, which amounted to 13.8 kg (percent total body weight loss: 20.95%), and was accompanied by a notable reduction in waist circumference (−14.1 cm). Moreover, body mass index (BMI)-based weight status improved from class 1 obesity to overweight: BMI value of 25.1 kg/m² at 8 months vs. 31.8 kg/m² at baseline (near-normalization of BMI values). Bioelectrical impedance analysis (BIA) revealed that the patient’s overall weight loss consisted of 74.6% fat mass (FM) loss (−10.3 kg) and 25.4% fat-free mass (FFM) loss (−3.5 kg). Despite the expected FFM reduction in absolute terms, percent FFM increased at 8 months (+9.6%). This increase in percent FFM was accompanied by a reduction in percent FM at 8 months (−9.6%), indicating an overall improvement in body composition. Normalization of percent FM and FFM values (28.6% and 71.4%, respectively) was also achieved at 8 months. These body composition changes are in line with those observed in clinical trials investigating the use of semaglutide in patients with overweight or obesity. At 6 months, an abdominal ultrasound also showed the disappearance of the sonographic characteristics suggestive of mild-to-moderate hepatic steatosis. Low-dose metformin (500 mg/day) and subcutaneous semaglutide (up to a weekly dose of 1.7 mg) were well tolerated by the patient. Conclusions: To the best of our knowledge, this is the first case documenting the effective use of once-weekly subcutaneous semaglutide plus low-dose metformin combination therapy for the treatment of obesity and prediabetes in a woman with a partial Xq deletion. Large prospective cohort studies are warranted to better investigate the safety and efficacy profile of semaglutide (alone or in combination with metformin) in patients with numerical and structural X chromosome abnormalities, comorbid overweight/obesity and related metabolic disorders. Full article

Osteoarthritis is the most common musculoskeletal disorder. It primarily affects people in their mid-40s and older. As the disease progresses, degenerative changes occur in the synovial membrane, subchondral bone, and cartilage. Ultimately, the entire joint and its surrounding tissues become structurally and functionally impaired. Several sets of biochemical markers have been proposed to enable timely diagnosis and anticipate disease progression. However, only a few of these markers are routinely used to evaluate disease activity in subgroups. We conducted a cross-sectional, single-center cohort study of 72 patients with knee osteoarthritis. Diagnoses were established based on clinical data and radiological findings. We examined two Wnt/β-catenin signaling inhibitors, serum DKK-1 and sclerostin, and two bone/cartilage metabolic regulatory factors, RANKL and OPG, correlating these with disease activity and pain scores (WOMAC, VAS, and KOFUS), radiographic stage, inflammatory molecules and indices, and bone mineral density. DKK-1 levels were higher in the intensive pain group (VAS > 5) and positively correlated with the KOFUS throughout the study. This correlation was stronger in individuals with a BMI < 30. Serum DKK-1 levels were higher in patients with lower bone mineral density. No significant modifications in SOST, RANKL, or OPG levels were found in any of the above settings. In our patient cohort with mild-to-moderate knee osteoarthritis (OA), sclerostin, osteoprotegerin (OPG), and receptor activator of nuclear factor kappa-B ligand (RANKL) were not related to pain or disease activity. In contrast, DKK-1 was an indicator of pain and low-grade flare-ups. Furthermore, DKK-1 was associated with the KOFUS and impaired bone turnover in non-obese subgroups. Confirming these relationships in larger groups of patients would contribute to more efficient use of DKK-1 in disease stratification algorithms. Full article

Background/Objectives: Risk for eating disorders (ED risk) in adolescents is strongly influenced by psychosocial factors, particularly family dysfunction. The COVID-19 pandemic may have intensified these risks by disrupting family dynamics and increasing stress exposure. This study aimed to examine the association between family dysfunction and ED risk among school adolescents in Lambayeque, Peru, in the post-pandemic context. Methods: An analytical cross-sectional study including 1219 students from five schools (September–December 2022) was conducted. ED risk was screened using the SCOFF questionnaire (≥2), and family functioning was assessed with the Family APGAR (functional, mild, moderate, or severe dysfunction). Additional sociodemographic, behavioral, and mental health variables were analyzed. Adjusted prevalence ratios (PRs) were estimated using Poisson regression with robust variance clustered by school. Results: The ED risk in adolescents was 39.3% (95% CI: 36.5–42.1). Moderate family dysfunction was reported in 10.0% and severe dysfunction in 29.8% of participants. In the multivariable model, moderate family dysfunction was associated with higher ED risk (PR = 1.11). Other factors associated with higher risk included obesity (PR = 1.17), family history of mental illness (PR = 1.18), course failure (PR = 1.18), alcohol consumption ≥4 times per week (PR = 1.75), and having a family member hospitalized due to COVID-19 (PR = 1.14). Protective associations were found for male sex, frequent contact with friends, higher resilience, and living in peri-urban areas. Conclusions: Moderate family dysfunction was associated with an increased at ED risk in adolescents. These findings highlight the importance of school-based screening, family-centered interventions, and resilience promotion in adolescent mental health strategies. Given the cross-sectional design, causal relationships cannot be inferred. Full article

Most dementias are preceded by mild cognitive impairment (MCI), a transitional clinical stage characterized by cognitive decline that does not yet significantly interfere with activities of daily living. Obesity and diabetes are among the major risk factors for MCI and are strongly associated with unhealthy lifestyle patterns. The growing global prevalence of obesity has intensified the need for effective dietary strategies that promote both weight control and neuroprotection. Red fruits, which are rich in bioactive compounds such as anthocyanins, have demonstrated potential roles in modulating metabolic pathways and cognitive function. This systematic review aimed to identify and synthesize evidence from human studies published over the past two decades that examined the effects of red fruit consumption on obesity-related mechanisms and cognitive outcomes, as well as its influence on key neurodegenerative biomarkers, including TAU protein, β-amyloid, and neurofilament light chain. A systematic search was conducted in major scientific databases to identify human clinical trials evaluating the metabolic and neuroprotective effects of berry-derived compounds. Eligible studies were screened for outcomes related to cognitive performance, obesity-related parameters, and relevant molecular biomarkers. The included studies reported modest improvements in cognitive domains, with the most consistent effects observed in memory-related outcomes. Berry-derived bioactive compounds demonstrated potential in attenuating TAU protein hyperphosphorylation and reducing β-amyloid accumulation; however, the available evidence remains limited and requires further confirmation. Human clinical studies remain scarce, and although some trials reported favorable metabolic effects, these findings are still inconclusive. Reported outcomes included improvements in insulin sensitivity, regulation of leptin levels, and modulation of the gut–brain axis, which may collectively contribute to a reduced risk of obesity. Based on the studies evaluated in this review, there remains a limited number of human clinical trials that robustly support the neuroprotective and complementary metabolic effects of berry-derived bioactive compounds. Nevertheless, the available evidence suggests that dietary strategies incorporating wild fruits rich in polyphenols may represent a promising complementary approach for the prevention of mild cognitive impairment (MCI) and obesity, with potential implications for reducing the risk of dementia progression. Full article

Obstructive sleep apnea (OSA) is a common disorder caused by recurrent upper airway obstruction during sleep, affecting individuals across the lifespan. In children, OSA commonly results from adenotonsillar hypertrophy and may resolve spontaneously or following surgical intervention. Among adolescents and adults, OSA is more frequently associated with modifiable lifestyle factors, particularly obesity. The natural history of OSA may evolve from intermittent snoring and mild disease to moderate or severe forms if left untreated, leading to reduced health-related quality of life and overall health deterioration. Early identification of OSA, especially in mild and moderate cases, allows timely interventions to improve OSA-associated indices and may prevent progression to severe disease. Continuous positive airway pressure therapy remains the treatment of choice for adults, providing effective symptom control and reducing long-term complications, although adherence rates vary. In obese patients, sustained weight reduction represents the most effective disease-modifying strategy: a ≥5% weight loss is associated with an approximately 80% reduction in progression risk, while bariatric surgery achieves remission in up to 60–65% of cases at one year. Emerging anti-obesity pharmacotherapies have also demonstrated clinically meaningful reductions in the apnea–hypopnea index. Comorbid conditions such as hypertension, type 2 diabetes, and depression exacerbate OSA severity, impair treatment response, and complicate overall disease management. This review uniquely integrates pediatric and adult longitudinal data, treatment-modified trajectories, and emerging therapeutic approaches to provide a life-course perspective on OSA natural history, highlighting opportunities for early, phenotype-directed intervention to possibly alter disease course and long-term outcomes. Full article