Journal of Obesity & Metabolic Syndrome最新文献

{"title":"Pharmacological Inhibition of Pyruvate Dehydrogenase Kinase 4 Enhances Insulin Sensitivity in Mouse Models of Diabetes and Obesity.","authors":"Min-Ji Kim, Bitna Ha, Ran Ryeong Kim, Jung-Yi Lee, Chae Won Lim, Jin Hee Ahn, In-Kyu Lee, Jae-Han Jeon","doi":"10.7570/jomes25086","DOIUrl":"10.7570/jomes25086","url":null,"abstract":"<p><strong>Background: </strong>Insulin resistance is a central feature of type 2 diabetes mellitus (T2DM), which remains a major global health burden with limited therapies that directly address upstream molecular defects. Pyruvate dehydrogenase kinase 4 (PDK4), a regulator of glucose and lipid metabolism, has emerged as a promising therapeutic target. Here, we evaluated the metabolic effects of GM-10395, an orally available PDK4 inhibitor, in preclinical models of insulin resistance.</p><p><strong>Methods: </strong>We evaluated the metabolic effects of GM-10395, an orally available PDK4 inhibitor, in preclinical models of insulin resistance. In alpha mouse liver 12 (AML12) hepatocytes, we assessed protein kinase B (AKT) phosphorylation, mitochondrial reactive oxygen species (ROS), and oxygen consumption rate (OCR). <i>In vivo</i>, long-term oral administration of GM-10395 (8 weeks in KKAy mice [n=6 per group] and 5 weeks in diet-induced obesity [DIO] mice [n=6 per group]) was evaluated for effects on glucose tolerance, glycosylated hemoglobin, lipid profiles, and liver histology.</p><p><strong>Results: </strong>GM-10395 restored AKT phosphorylation, reduced ROS generation, and normalized OCR in palmitate-treated AML12 cells. In both KKAy and DIO mice, GM-10395 significantly improved glucose tolerance and reduced hepatic steatosis. Serum lipid analysis revealed reductions in low-density lipoprotein cholesterol and triglycerides, with histology confirming decreased lipid deposition. Enhanced insulin signaling, evidenced by increased phosphorylated AKT/total AKT ratios in liver, muscle, and adipose tissues, was consistently observed.</p><p><strong>Conclusion: </strong>GM-10395 improves systemic glucose and lipid homeostasis by restoring insulin sensitivity via PDK4 inhibition. These results support GM-10395 as a promising oral therapeutic candidate for insulin resistance in T2DM.</p>","PeriodicalId":45386,"journal":{"name":"Journal of Obesity & Metabolic Syndrome","volume":" ","pages":"247-258"},"PeriodicalIF":7.9,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145865874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Clinical Analysis of DPP-4 inhibitors and SGLT2 Inhibitors: A Real-World Switch Study.","authors":"Hun Jee Choe, Mi Kyung Kwak, Ji Woo Lee, Yun Mi Choi, Eun-Gyoung Hong","doi":"10.7570/jomes25049","DOIUrl":"10.7570/jomes25049","url":null,"abstract":"<p><strong>Background: </strong>Dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium-glucose co-transporter 2 (SGLT2) inhibitors are contemporary oral antidiabetic medications, each offering distinct advantages and challenges. Understanding their comparative effectiveness in real-world settings is crucial for optimizing treatment strategies.</p><p><strong>Methods: </strong>We retrospectively analyzed adults with type 2 diabetes mellitus who switched between DPP-4 inhibitors and SGLT2 inhibitors from December 1, 2014, to November 26, 2023, using a clinical data warehouse. All participants had baseline glycosylated hemoglobin (HbA1c) levels between 6.5% and 10.0% and were receiving metformin. To reduce baseline imbalance in HbA1c and fasting plasma glucose (FPG), we excluded patients with an estimated glomerular filtration rate <45 mL/min/1.73 m² and performed 1:1 propensity-score matching on baseline levels of HbA1c and FPG. The matched cohort included 168 patients (84 per group). The primary outcome was the between-group difference in change in HbA1c over 3 months. Secondary outcomes were changes in FPG, body mass index (BMI), liver enzymes, and renal function.</p><p><strong>Results: </strong>Switching to DPP-4 inhibitors was associated with a greater reduction in HbA1c (β, -0.26; 95% confidence interval [CI], -0.51 to -0.01; <i>P</i><0.001). In contrast, switching to SGLT2 inhibitors led to significant improvements in FPG (β, 10.50; 95% CI, 0.22 to 20.78; <i>P</i><0.001) and liver enzyme levels. Older patients and those with a lower BMI, higher baseline HbA1c, or chronic kidney disease derived greater benefit from switching to DPP-4 inhibitors.</p><p><strong>Conclusion: </strong>Transitioning to DPP-4 inhibitors reduced HbA1c levels significantly, whereas switching to SGLT2 inhibitors improved FPG and liver-related metabolic parameters.</p>","PeriodicalId":45386,"journal":{"name":"Journal of Obesity & Metabolic Syndrome","volume":" ","pages":"237-246"},"PeriodicalIF":7.9,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147595408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic Phenotypes and the Risk of Cancer Occurrence: A Prospective Cohort Study with 18-Year Follow-up.","authors":"Mahdieh Golzarand, Nazanin Moslehi, Farhad Hosseinpanah, Parvin Mirmiran, Fereidoun Azizi","doi":"10.7570/jomes25024","DOIUrl":"10.7570/jomes25024","url":null,"abstract":"<p><strong>Background: </strong>Current evidence concerning a link between metabolic phenotypes and their dynamic changes over time and the risk of cancer is limited. The present study aimed to assess the association between different metabolic health statuses and the risk of cancer occurrence among adult individuals.</p><p><strong>Methods: </strong>This prospective cohort study enrolled 11,445 adults aged ≥18 years from the Tehran Lipid and Glucose Study and followed them for 18 years. We identified metabolic phenotypes based on the Joint Interim Statement. Accordingly, participants were divided into four groups: metabolically healthy normal weight/overweight (MHNW/OW), metabolically unhealthy normal weight/overweight (MUNW)/OW, metabolically healthy obesity (MHO), and metabolically unhealthy obesity (MUO). Cox proportional hazards modeling was performed to assess the association between metabolic phenotype and the risk of cancer occurrence.</p><p><strong>Results: </strong>The multivariable adjusted hazard ratio (HR) (95% confidence interval [CI]) for cancer risk in participants with the MUNW/OW phenotype was 1.37 (95% CI, 1.04 to 1.82) and that in those with the MUO phenotype was 1.84 (95% CI, 1.21 to 2.79) when compared to those with the MHNW/OW phenotype, respectively. More particularly, the risk of breast cancer was higher in women with the MHO phenotype (HR, 3.60; 95% CI, 1.34 to 9.60) as well as those with the MUO phenotype (HR, 4.69; 95% CI, 1.96 to 11.20) relative to those with the MHNW/OW phenotype. Ultimately, however, we found no relationship between phenotype transition and the risk of cancer occurrence.</p><p><strong>Conclusion: </strong>Based on our findings, metabolically unhealthy phenotypes may be associated with a higher overall incidence of cancer. In addition, obesity, independent of metabolic status, was linked to an increased risk of breast cancer incidence. No association between the transition from a metabolically healthy to unhealthy phenotype and cancer risk was established.</p>","PeriodicalId":45386,"journal":{"name":"Journal of Obesity & Metabolic Syndrome","volume":" ","pages":"188-197"},"PeriodicalIF":7.9,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145906823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current Trends and Perspectives on Obesity and Metabolic Dysfunction-Associated Steatohepatitis in East Asia.","authors":"Soo Lim, Hui Zhou, Wataru Ogawa","doi":"10.7570/jomes25083","DOIUrl":"10.7570/jomes25083","url":null,"abstract":"<p><p>Obesity is a global epidemic that has rapidly increased in prevalence in East Asian countries. Complications of obesity, such as metabolic dysfunction-associated steatohepatitis (MASH), have increased in parallel with the recent rise in obesity. Rapidly aging populations, increasingly Westernized lifestyles, and a likelihood of developing higher-risk fat types (e.g., visceral adipose tissue) all play a role in the rising influence of obesity and MASH in East Asian populations. Additionally, East Asian patients are at high risk for developing lean MASH at lower body mass indexes than are common in Western populations. Tools to specifically detect and diagnose MASH in East Asia are lacking. Non-invasive tests (NITs) used globally to detect MASH have inadequate evidence of efficacy in East Asian populations. Current treatment strategies are also inadequate, with East Asian patients largely underrepresented in obesity and MASH clinical trials. Given large, diverse healthcare systems and a lack of awareness and infrastructure to support prevention and long-term management, obesity and MASH are rapidly becoming serious public health concerns in these countries. Therefore, both patients and physicians need better awareness of obesity and MASH, improved access to NITs to diagnose MASH, and more effective treatment options than they currently have. Educational methods should be developed to improve awareness, and more clinical studies of NITs and treatments in East Asian populations are needed.</p>","PeriodicalId":45386,"journal":{"name":"Journal of Obesity & Metabolic Syndrome","volume":" ","pages":"130-149"},"PeriodicalIF":7.9,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147345225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effects of Probiotic Yogurt and Resistance Training on Body Composition and Metabolic Parameters in Post-bariatric Surgery Patients: A Randomized Controlled Trial.","authors":"Shirin Rajabi, Moein Askarpour, Neda Haghighat, Mohammad Hadi Eskandari, Babak Hosseini, Seyed Vahid Hosseini, Reza Bagheri, Mandana Famouri, Siavash Babajafari","doi":"10.7570/jomes25045","DOIUrl":"10.7570/jomes25045","url":null,"abstract":"<p><strong>Background: </strong>Bariatric surgery (BS) is an effective intervention for morbid obesity; however, it is often accompanied by undesirable muscle mass loss, which can negatively affect metabolic function and physical performance. Probiotics and resistance training (RT) have been studied discretely to address this complication. The present randomized controlled trial investigated the independent and combined effects of fortified yogurt (FY) and RT on muscle preservation and related health outcomes in post-BS patients.</p><p><strong>Methods: </strong>In this parallel, randomized controlled trial, 52 participants who had recently undergone BS and met the eligibility criteria were randomly assigned to one of four groups: group A (FY+RT), group B (FY), group C (RT), and group D (control), with 13 participants in each group. Anthropometric indices, body composition, functional performance, inflammatory and oxidative stress markers, lipid profile, and liver enzymes were measured at baseline and after a 12-week intervention.</p><p><strong>Results: </strong>All participants completed the intervention. The FY+RT group showed the greatest preservation of muscle mass, with the smallest reductions in fat-free mass percentage (-2.32%, <i>P</i>=0.001) and skeletal muscle mass (-1.34 kg, <i>P</i><0.001). This group also exhibited significant improvements in muscle strength, as measured by hand grip strength (<i>P</i>=0.038) and 30-second chair stand test repetitions (<i>P</i><0.001).</p><p><strong>Conclusion: </strong>The combination of FY and RT was the most effective strategy for preserving muscle mass and improving strength following BS. Further research is warranted to elucidate the underlying mechanisms and validate these findings.</p>","PeriodicalId":45386,"journal":{"name":"Journal of Obesity & Metabolic Syndrome","volume":" ","pages":"222-236"},"PeriodicalIF":7.9,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145912756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucagon-Like Peptide-1 Receptor Agonists and Ocular Outcomes: Metabolic Transition, Retinal Vulnerability, and Risk-Stratified Monitoring.","authors":"Su Jeong Song, EunAh Kim","doi":"10.7570/jomes26012","DOIUrl":"https://doi.org/10.7570/jomes26012","url":null,"abstract":"<p><p>Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual incretin-based therapies provide marked reductions in glycosylated hemoglobin (HbA1c), body weight, and cardiovascular risk. As global adoption expands and recognition of their broad metabolic benefits grows, clinical attention is shifting toward potential secondary complications, including ocular manifestations, during rapid metabolic improvement. This narrative review synthesizes evidence from randomized trials, meta-analyses, and observational studies up to 2026 to evaluate the effects of GLP-1-based therapies on various ocular outcomes. Recent meta-analyses demonstrate an overall neutral long-term risk for diabetic retinopathy (DR) and macular edema. Transient early worsening of DR occurs primarily in patients with advanced baseline disease and rapid HbA1c reductions, reflecting a metabolic transition phenomenon rather than intrinsic retinal toxicity. This interpretation is supported by 2024 cardiovascular outcome data in a non-diabetic population (e.g., Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity [SELECT] trial) that showed no increased ocular risk. Observational data suggest protective associations with glaucoma via intraocular pressure-independent neuroprotection and a reduced risk of incident age-related macular degeneration, but a potential safety signal for nonarteritic anterior ischemic optic neuropathy has emerged in recent datasets. Although the absolute incidence remains low, risk with a delayed temporal pattern appears to be increased in specific cohorts. Emerging evidence also suggests potential benefits in ocular surface homeostasis and uveitis. Accordingly, following a 2025 multidisciplinary expert consensus, risk-stratified ophthalmic monitoring, rather than routine treatment avoidance, is recommended during the early metabolic transition in high-risk diabetic patients.</p>","PeriodicalId":45386,"journal":{"name":"Journal of Obesity & Metabolic Syndrome","volume":"35 2","pages":"164-175"},"PeriodicalIF":7.9,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147785092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the Safety Profile of Glucagon-Like Peptide-1 Receptor Agonists: Adverse Events and Clinical Recommendations.","authors":"Mi Kyung Kim, Eun Yeong Ha, Hye Soon Kim","doi":"10.7570/jomes25081","DOIUrl":"10.7570/jomes25081","url":null,"abstract":"<p><p>The rising global prevalence of obesity and its associated health problems necessitate effective intervention strategies. Historically, many anti-obesity medications have been developed and later withdrawn because of unfavorable adverse event profiles. By contrast, recently introduced glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) demonstrate remarkable efficacy for weight loss. Furthermore, they confer beneficial effects on cardiovascular and renal outcomes and metabolic dysfunction-associated liver disease. Despite these benefits, adverse events such as retained gastric content and pulmonary aspiration remain a concern. Consequently, this review summarizes current evidence and offers clinical guidance on GLP-1 RA-related adverse effects.</p>","PeriodicalId":45386,"journal":{"name":"Journal of Obesity & Metabolic Syndrome","volume":" ","pages":"150-163"},"PeriodicalIF":7.9,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147445489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic Impact of Sodium-Glucose Cotransporter 2 Inhibitor-Induced Ketogenesis in Type 2 Diabetes Mellitus.","authors":"Hee Woo Park, Hun Jee Choe, Ho Jun Lim, Sung Hye Kong, Tae Jung Oh, Min Joo Kim, Jae Hoon Moon, Sung Hee Choi, Soo Lim, Joon Ho Moon","doi":"10.7570/jomes25062","DOIUrl":"10.7570/jomes25062","url":null,"abstract":"<p><strong>Background: </strong>Sodium-glucose cotransporter 2 (SGLT2) inhibitors improve glycemic control and confer cardiovascular and renal benefits in individuals with type 2 diabetes mellitus (T2DM) partly by promoting urinary glucose excretion and modulating energy metabolism. However, the clinical relevance of ketogenesis induced by SGLT2 inhibitors remains unclear.</p><p><strong>Methods: </strong>This retrospective cohort study was conducted at the Seoul National University Bundang Hospital, South Korea. In total, 151 adults with T2DM who were newly treated with SGLT2 inhibitors (empagliflozin or dapagliflozin) between November 2021 and June 2024 were enrolled. Glycemic parameters (glycosylated hemoglobin [HbA1c], body mass index [BMI], and fasting plasma glucose [FPG]) as well as metabolic profiles (lipid profile, renal function, and hepatic function) were assessed at baseline and after 6 months of treatment. The participants were stratified into tertiles based on the relative increase in serum ketone levels.</p><p><strong>Results: </strong>SGLT2 inhibitor treatment significantly improved HbA1c, FPG, BMI, insulin sensitivity, and the lipid profile. Mean serum ketone levels increased from 92.7±69.4 to 173.5±172.6 μmol/L (<i>P</i><0.001), although with substantial inter-individual variability. Although ketone elevation did not independently predict HbA1c reduction, participants with elevated ketone responses exhibited enhanced FPG reduction, higher urinary glucose excretion, and favorable triglyceride reduction, suggesting metabolic benefits. A moderate decline in kidney function was also observed in these participants.</p><p><strong>Conclusion: </strong>Ketogenesis did not independently predict HbA1c reduction; however, elevated ketone levels following SGLT2 inhibitor treatment were associated with favorable metabolic adaptations, suggesting potential extra-glycemic benefits.</p>","PeriodicalId":45386,"journal":{"name":"Journal of Obesity & Metabolic Syndrome","volume":" ","pages":"211-221"},"PeriodicalIF":7.9,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147345219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response: Ultra-Processed Food Consumption and Obesity: A Narrative Review of Their Association and Potential Mechanisms (J Obes Metab Syndr 2025;34:27-40).","authors":"Jee-Seon Shim","doi":"10.7570/jomes26011","DOIUrl":"10.7570/jomes26011","url":null,"abstract":"","PeriodicalId":45386,"journal":{"name":"Journal of Obesity & Metabolic Syndrome","volume":" ","pages":"261-263"},"PeriodicalIF":7.9,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147628936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter: Ultra-Processed Food Consumption and Obesity: A Narrative Review of Their Association and Potential Mechanisms (J Obes Metab Syndr 2025;34:27-40).","authors":"Jose M Moris","doi":"10.7570/jomes25069","DOIUrl":"10.7570/jomes25069","url":null,"abstract":"","PeriodicalId":45386,"journal":{"name":"Journal of Obesity & Metabolic Syndrome","volume":" ","pages":"259-260"},"PeriodicalIF":7.9,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147345241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}