Diabetes & Metabolism Journal最新文献

{"title":"Enavogliflozin, an SGLT2 Inhibitor, Improves Nonalcoholic Steatohepatitis Induced by High-Fat, High-Cholesterol Diet.","authors":"Phuc Thi Minh Pham, Giang Nguyen, So Young Park, Thuy Linh Lai, Dae-Hee Choi, Jeana Hong, Seon Mee Kang, Eun-Hee Cho","doi":"10.4093/dmj.2024.0259","DOIUrl":"https://doi.org/10.4093/dmj.2024.0259","url":null,"abstract":"<p><strong>Background: </strong>Nonalcoholic fatty liver disease, a progressive condition caused by the accumulation of fat in the liver, begins with simple steatosis and can potentially progress to metabolic dysfunction-associated steatohepatitis (MASH) in the presence of inflammation and fibrosis, ultimately leading to cirrhosis or hepatocellular carcinoma. Increasing evidence indicates that sodiumglucose cotransporter 2 (SGLT2) inhibitors effectively alleviate MASH in mouse models. However, there is a lack of research on the effects of enavogliflozin on liver disease. In the present study, we investigated the effects of SGLT2 inhibitors on MASH induced by a high-fat, high-cholesterol (HFHC) diet in mice.</p><p><strong>Methods: </strong>Male C57BL/6 mice were fed a normal chow diet, HFHC diet, or HFHC diet with enavogliflozin for 12 weeks. LX-2 and HepG2 cells were treated with enavogliflozin in the presence of various pathological stimuli.</p><p><strong>Results: </strong>The HFHC diet induced excessive hepatic lipid accumulation, inflammation, and severe fibrosis. Administration of enavogliflozin not only ameliorated hepatic steatosis and fibrotic conditions but also suppressed the production of inflammatory cytokines. Positive outcomes were also observed in in vitro experiments, where enavogliflozin demonstrated the ability to impede the activation of hepatic stellate cells and alleviate lipid accumulation in hepatocytes. The potential pathway through which enavogliflozin attenuated liver fibrosis development may be associated with the transforming growth factor β1/Smad signaling pathway.</p><p><strong>Conclusion: </strong>Our results suggest that enavogliflozin is effective in a mouse model of MASH by attenuating hepatic steatosis, suppressing inflammation, and improving liver fibrosis.</p>","PeriodicalId":11153,"journal":{"name":"Diabetes & Metabolism Journal","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differences between Type 2 Diabetes Mellitus and Obesity Management: Medical, Social, and Public Health Perspectives.","authors":"Soo Lim, Ga Eun Nam, Arya M Sharma","doi":"10.4093/dmj.2025.0278","DOIUrl":"https://doi.org/10.4093/dmj.2025.0278","url":null,"abstract":"<p><p>Obesity and type 2 diabetes mellitus (T2DM) are among the most urgent global public health challenges, yet differ markedly in recognition and management across medical, social, infrastructure, and policy domains. T2DM is supported by clear diagnostic criteria, defined treatment targets, and broad acceptance as a chronic disease. In contrast, obesity is assessed using imprecise metrics like body mass index, lacks standardized treatment goals, and is often misunderstood as a lifestyle issue rather than a chronic, relapsing disease. This misconception contributes to stigma, discrimination, and unrealistic patient expectations. T2DM receives substantial research funding, comprehensive clinical guidelines, and structured medical education, with strong support from large professional societies and multidisciplinary care models. Obesity care remains underfunded, inconsistently delivered, and underrepresented in medical training. Public health and policy efforts strongly favor T2DM, providing coordinated programs, insurance coverage, and regulatory oversight. Conversely, obesity is marginalized, with limited policy influence and a largely unregulated commercial weight-loss industry. Bridging these disparities requires adopting lessons from T2DM management-such as evidence-based guidelines, improved provider training, expanded insurance coverage, and public health strategies-to enhance obesity care and recognize it as a chronic disease requiring long-term, structured management.</p>","PeriodicalId":11153,"journal":{"name":"Diabetes & Metabolism Journal","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ultra-Processed Food Intake and Risk of Type 2 Diabetes Mellitus: A Dose-Response Meta-Analysis of Prospective Studies.","authors":"Yujin Kim, Yoonkyoung Cho, Jin Eui Kim, Dong Hoon Lee, Hannah Oh","doi":"10.4093/dmj.2024.0706","DOIUrl":"https://doi.org/10.4093/dmj.2024.0706","url":null,"abstract":"<p><strong>Background: </strong>Although some studies suggest a positive association between ultra-processed food (UPF) intake and type 2 diabetes mellitus (T2DM), little is known about the exact shape and risks associated with different units (percentage of g/day, absolute g/day, serving/day) of UPF intake and whether the association is independent of diet quality, total energy intake, and body mass index (BMI).</p><p><strong>Methods: </strong>Prospective studies published through January 2024 were identified by searching PubMed, Embase, and Web of Science. Summary relative risks (RRs) and 95% confidence intervals (CIs) were estimated using random-effects models. A nonlinear dose-response meta-analysis was conducted using restricted cubic spline analysis.</p><p><strong>Results: </strong>After screening 569 publications, a total of 12 prospective cohort studies were included. Comparing the highest vs. lowest categories of intake, summary RR for T2DM risk was 1.48 (95% CI, 1.36 to 1.61). Higher summary RRs were observed among studies from Europe and North America. Among individual UPF subgroups, processed meats (summary RR, 1.34; 95% CI, 1.16 to 1.54) were positively associated, whereas ultra-processed cereals and breads (0.98; 95% CI, 0.97 to 0.99) and packaged savory snacks (0.92; 95% CI, 0.88 to 0.95) were inversely associated. The summary RRs associated with every 10% (of g/day), 100-g/day, and 1-serving/day increase in UPF intake were 1.14 (95% CI, 1.11 to 1.17), 1.05 (95% CI, 1.03 to 1.06), and 1.04 (95% CI, 1.03 to 1.05), respectively. The dose-response curve for absolute g/d intake suggested nonlinearity, showing a steeper risk increase approximately at >300 g/day. The associations persisted after adjustment for diet quality, energy intake, or BMI.</p><p><strong>Conclusion: </strong>Our data suggest that UPF intake increases diabetes risk, with a potential threshold effect at 300 g/day.</p>","PeriodicalId":11153,"journal":{"name":"Diabetes & Metabolism Journal","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing Nutritional Factors for Metabolic Dysfunction-Associated Steatotic Liver Disease via Diverse Statistical Tools.","authors":"Yea-Chan Lee, Hye Sun Lee, Soyoung Jeon, Yae-Ji Lee, Yu-Jin Kwon, Ji-Won Lee","doi":"10.4093/dmj.2025.0026","DOIUrl":"https://doi.org/10.4093/dmj.2025.0026","url":null,"abstract":"<p><strong>Background: </strong>Lifestyle modifications are critical in addressing metabolic dysfunction-associated steatotic liver disease (MASLD); however, the specific macronutrients that most significantly influence the disease's progression are uncertain. In this study, we aimed to explore the role of carbohydrate, fat, and protein intake in MASLD development using decision trees, random forest models, and cluster analysis.</p><p><strong>Methods: </strong>Participants (n=3,951) from the Korean Genome and Epidemiology Study were included. We used the classification and regression tree analysis to classify participants into subgroups based on variables associated with the incidence of new-onset MASLD. Random forest analyses were used to assess the relative importance of each variable. Participants were grouped into homogeneous clusters based on carbohydrate, protein, fat, and total caloric intake using hierarchical cluster analysis. Subsequently, we used the Cox proportional hazards regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for MASLD risk across the clusters.</p><p><strong>Results: </strong>Carbohydrate intake was identified as the most significant predictor of new-onset MASLD, followed by fat, protein, and total caloric intake. Participants in cluster 3, who consumed a lower proportion of carbohydrate but had higher total caloric, protein, and fat intake, had a lower risk of new-onset MASLD than those in cluster 1 after adjusting for confounders (cluster 1 as a reference; cluster 3: HR, 0.90; 95% CI, 0.82 to 0.99).</p><p><strong>Conclusion: </strong>The study's results highlight the critical role of macronutrient composition, particularly carbohydrate intake, in MASLD development. The findings suggest that dietary strategies focusing on optimizing macronutrients, rather than simply reducing caloric intake, may be more effective in preventing MASLD.</p>","PeriodicalId":11153,"journal":{"name":"Diabetes & Metabolism Journal","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Efficacy of Initial Statin and Ezetimibe Combination versus Statin Monotherapy on Cardiovascular Outcomes in Diabetes Mellitus: A Nationwide Cohort Study.","authors":"Minji Sohn, Young-Hwan Park, Soo Lim","doi":"10.4093/dmj.2024.0482","DOIUrl":"https://doi.org/10.4093/dmj.2024.0482","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to assess the efficacy of an initial combination therapy of statin and ezetimibe compared with statin monotherapy on major cardiovascular outcomes in individuals with diabetes.</p><p><strong>Methods: </strong>In this population-based cohort study using National Health Insurance Service data (2010-2020), we included adults with diabetes who had not previously used any lipid-lowering medications. Those initiating statin monotherapy were matched 1:1 using propensity scores with patients starting combination therapy with a lower-potency statin and ezetimibe. This matching process resulted in 21,458 individuals in the primary prevention cohort and 10,094 in the secondary prevention cohort, respectively. The primary endpoint was a composite of myocardial infarction, stroke, and cardiovascular death. Hospitalizations for heart failure, angina, and all-cause mortality were analyzed. The impact of ezetimibe maintenance on the primary endpoint was analyzed, and other hospitalizations were categorized as adverse events.</p><p><strong>Results: </strong>Compared with statin monotherapy, statin-ezetimibe combination significantly reduced the incidence of the primary endpoint (4.85 vs. 3.25 per 1,000 person-years: hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.56 to 0.81 in the primary cohort; and 19.5 vs. 15.7 per 1,000 person-years: HR, 0.80; 95% CI, 0.70 to 0.91 in the secondary cohort) and myocardial infarction (HR, 0.64; 95% CI, 0.46 to 0.82 in the primary cohort; and HR, 0.73; 95% CI, 0.60 to 0.89 in the secondary cohort). A longer maintenance period of ezetimibe was significantly related to better efficacy in the composite cardiovascular outcomes. High-intensity statin monotherapy was associated with an elevated risk of liver, muscle, and diabetes-related hospitalization in the primary prevention cohort.</p><p><strong>Conclusion: </strong>Initial therapy with a statin-ezetimibe combination is associated with a reduced risk of cardiovascular events and fewer adverse events compared to statin monotherapy in individuals with diabetes, over a mean follow-up of 5.5 years (up to 9 years).</p>","PeriodicalId":11153,"journal":{"name":"Diabetes & Metabolism Journal","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Insights into the Causal Relationship between Antidiabetic Drugs and Adverse Perinatal Outcomes: A Mendelian Randomization Study.","authors":"Chang Su, Xueqing He, Xiaona Chang, Juan Tian, Guang Wang, Jia Liu","doi":"10.4093/dmj.2024.0521","DOIUrl":"https://doi.org/10.4093/dmj.2024.0521","url":null,"abstract":"<p><strong>Background: </strong>Hyperglycemia during pregnancy increases the risk of adverse perinatal outcomes and birth defects. Evidence regarding the long-term safety of antidiabetic drugs during pregnancy is still lacking.</p><p><strong>Methods: </strong>A two-sample Mendelian randomization (MR) study was performed to assess the causal association between six antidiabetic drug targets (ABCC8, DPP4, INSR, GLP1R, PPARG, and SLC5A2) and seven adverse perinatal outcomes and five congenital malformation outcomes. Inverse variance weighted (IVW) was adopted as the main MR method, and sensitivity analysis using traditional MR methods was performed to evaluate the robustness of the results.</p><p><strong>Results: </strong>We observed strong evidence that sodium-glucose cotransporter 2 (SGLT2) inhibitors (odds ratio [OR], 0.084; 95% confidence interval [CI], 0.009 to 0.834; P=0.034) reduces the risk of preterm birth; genetic variation in sulfonylurea drug targets (OR, 0.015; 95% CI, 2.50E-04 to 0.919; P=0.045) and genetic variation in thiazolidinedione drug targets (OR, 0.007; 95% CI, 4.16E-04 to 0.121; P=0.001) reduced the risk of eclampsia/preeclampsia; glucagon-like peptide 1 (GLP-1) analogues target (β=-0.549; 95% CI, -0.958 to -0.140; P=0.009) was inversely associated with fetal birth weight; thiazolidinedione target was inversely associated with gestational age (β=-0.952; 95% CI, -1.785 to -0.118; P=0.025); SGLT2 inhibitors reduced the risk of cardiocirculatory malformations (OR, 0.001; 95% CI, 8.75E-06 to 0.126; P=0.005).</p><p><strong>Conclusion: </strong>Most antidiabetic drugs are safe when used during the perinatal period. Of note, GLP-1 analogues may lead to a risk of low birth weight, while thiazolidinediones may lead to a reduction in fetal gestational age.</p>","PeriodicalId":11153,"journal":{"name":"Diabetes & Metabolism Journal","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First Trimester Mean Glucose Level on Continuous Glucose Monitoring Is Associated with Infant Birth Weight.","authors":"Phaik Ling Quah, Lay Kok Tan, Serene Pei Ting Thain, Ngee Lek, Shephali Tagore, Bernard Su Min Chern, Seng Bin Ang, Ann Wright, Michelle Jong, Kok Hian Tan","doi":"10.4093/dmj.2024.0700","DOIUrl":"https://doi.org/10.4093/dmj.2024.0700","url":null,"abstract":"<p><strong>Background: </strong>Comparisons between continuous glucose monitoring (CGM) metrics during the first and second trimesters and conventional mid-pregnancy oral glucose tolerance test (OGTT) values in pregnant women without pre-existing diabetes for predicting infant birth weight are scarce.</p><p><strong>Methods: </strong>In a longitudinal observational study, 113 participants had first and second trimester CGM data collected over a 7- to 14-day period, as well as three-point OGTT (fasting, 1-hour, and 2-hour) performed at mid-pregnancy (24 to 28 weeks). Multinomial logistic regression, adjusting for maternal ethnicity, education level, age, pre-pregnancy body mass index, parity, gestational diabetes mellitus diagnosis, gestational age at delivery, and type of CGM sensor was used to analyse the relationship between CGM metrics, OGTT glucose values and infant birth weight tertile (Clinical trial identification number: NCT05123248).</p><p><strong>Results: </strong>In the univariate analysis, CGM-derived metrics including higher mean glucose in the first trimester, higher % time above range in the second trimester, and higher % time in range (TIR) and lower % time below range (TBR) in both the first and second trimesters were associated with infants in the highest birth weight tertile. After adjusting for confounders, a 1-standard deviation increase in mean glucose level during the first trimester was significantly associated with the likelihood of the neonatal birthweight being in the highest tertile (adjusted odds ratio, 3.11; 95% confidence interval, 1.18 to 8.21; P=0.022). No significant associations were found between OGTT glucose values and infant birth weight outcomes.</p><p><strong>Conclusion: </strong>CGM-derived mean glucose levels in early pregnancy may be a better predictor of an infant's birth weight within the highest tertile, compared to mid-pregnancy OGTT glucose values.</p>","PeriodicalId":11153,"journal":{"name":"Diabetes & Metabolism Journal","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Birth Weight, Cardiovascular Health, and Microvascular Complications in Individuals with Diabetes Mellitus.","authors":"Chaolun Yu, Anping Feng, Xia Zou, Siqi Chen, Lingyan Dai, Qingmei Cui, Xiaojing Kuang, Gaoli She, Ying Ma, Haixia Guan, Jie Li","doi":"10.4093/dmj.2024.0518","DOIUrl":"https://doi.org/10.4093/dmj.2024.0518","url":null,"abstract":"<p><strong>Background: </strong>Diabetes often leads to microvascular complications, including nephropathy, neuropathy, and retinopathy. Understanding the impact of early-life factors like birth weight and modifiable behaviors such as cardiovascular health (CVH) is essential for preventing these complications.</p><p><strong>Methods: </strong>We included 11,515 participants with diabetes but without microvascular complications at baseline from the UK Biobank Study. CVH was evaluated using the Life's Essential 8 score. Independent and joint associations of birth weight and CVH with microvascular complications were analyzed using Cox proportional hazard models. Two-sample Mendelian randomization (MR) analyses estimated unconfounded associations between birth weight and microvascular complications.</p><p><strong>Results: </strong>Over a median follow-up of 13.1 years, 3,010 microvascular complications occurred. Compared with normal birth weight (2.5-4.0 kg), low birth weight (LBW; <2.5 kg) was associated with 15% higher risk of diabetic nephropathy (hazard ratio [HR], 1.15; 95% confidence interval [CI], 1.01 to 1.31), but not with neuropathy and retinopathy. High birth weight (>4.0 kg) was not associated with the risk of diabetic microvascular complications. MR analysis confirmed the association between LBW and nephropathy. Adherence to high CVH was associated with a reduced risk of microvascular complications compared to low CVH, regardless of birth weight. The HRs were 0.70 (95% CI, 0.59 to 0.84) for the LBW group and 0.74 (95% CI, 0.68 to 0.80) for the group with birth weight ≥2.5 kg (P for interaction=0.69).</p><p><strong>Conclusion: </strong>LBW was an independent risk factor for nephropathy among diabetic patients. However, the detrimental effects of LBW might be mitigated by improvement in CVH.</p>","PeriodicalId":11153,"journal":{"name":"Diabetes & Metabolism Journal","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phosphodiesterase 5 Inhibitor Improves Insulin Sensitivity by Regulating Adipose Tissue Macrophage Polarization in Diet-Induced Obese Mice.","authors":"Dan-Gyeong Song, Seongwon Pak, Dae-Chul Shin, Shindy Soedono, Kae Won Cho, Yejin Park, Subin Moon, Sooyeon Jang, Saeha Kim, Sang-Won Han, Keunwook Lee, Jong-Hee Sohn, Chan Hee Lee","doi":"10.4093/dmj.2024.0308","DOIUrl":"https://doi.org/10.4093/dmj.2024.0308","url":null,"abstract":"<p><strong>Background: </strong>Obesity is a rapidly increasing global health issue, which is associated with glucose and insulin resistance. Phosphodiesterase type 5 (PDE5) inhibitors (PDE5i) are known for their ability to enhance blood flow and vascular stability and are widely used to treat conditions such as erectile dysfunction, pulmonary hypertension, heart failure, and cancer. However, studies investigating the role of PDE5i in alleviating obesity and metabolic diseases remains unclear. Therefore, we investigated the effects of PDE5i on obesity and metabolic disorders in diet-induced obese mice and its underlying mechanisms.</p><p><strong>Methods: </strong>PDE5i was administered to high-fat diet (HFD)-fed C57BL/6J mice for 6 to 7 weeks. Body weight and food intake were measured weekly, and baseline metabolic rates, physical activity, and glucose and insulin tolerance tests were assessed during PDE5i administration. Macrophages and T-cells in the gonadal white adipose tissue (gWAT) were analyzed by flow cytometry. Vascular stability and blood flow in gWAT were analyzed via immunostaining and in vivo live imaging. RAW264.7 cells and bone marrow-derived macrophages were used to determine immunoregulatory effects of PDE5i.</p><p><strong>Results: </strong>In HFD-fed mice, PDE5i administration significantly enhanced systemic insulin sensitivity and AKT phosphorylation in gWAT. PDE5i reduced the M1/M2 ratio of gWAT macrophages of obese mice. These phenomena were associated with enhanced blood flow to the gWAT. In vitro experiments revealed that PDE5i suppressed lipopolysaccharide-induced proinflammatory cytokine production and increased the mRNA expression of genes associated with M2 polarization.</p><p><strong>Conclusion: </strong>PDE5i plays a role in regulating adipose tissue inflammation and thus holds promise as a therapeutic agent for metabolic enhancement.</p>","PeriodicalId":11153,"journal":{"name":"Diabetes & Metabolism Journal","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-Senescence Effect of Inhibiting Sodium-Glucose Cotransporter 2 and α-Glucosidase in a Type 2 Diabetes Mellitus Animal Model.","authors":"Serin Hong, Byung Soo Kong, Hyunsuk Lee, Young Min Cho","doi":"10.4093/dmj.2024.0339","DOIUrl":"https://doi.org/10.4093/dmj.2024.0339","url":null,"abstract":"<p><strong>Background: </strong>The prevalence of type 2 diabetes mellitus (T2DM) increases with age, and cellular senescence of pancreatic β-cells plays a key role in T2DM pathogenesis. As canagliflozin and acarbose have been shown to increase lifespan in mice, we investigated the effect of sodium-glucose cotransporter 2 (SGLT2) inhibitor, α-glucosidase inhibitor or both on the cellular senescence of β-cells in a T2DM mouse model.</p><p><strong>Methods: </strong>Enavogliflozin (0.3 mg/kg), acarbose (10 mg/kg), or vehicle was orally administered daily to db/db mice for 6 weeks. The levels of senescence markers (p16, p21, and p53) in the pancreas and kidney were measured through real-time polymerase chain reaction (PCR), immunofluorescence staining, and Western blot. In an in vitro analysis, isolated pancreatic islets were exposed to H2O2 to induce cellular senescence, then treated with β-hydroxybutyrate (β-HB), and subsequently assessed for levels of senescent markers.</p><p><strong>Results: </strong>Enavogliflozin alone or combined with acarbose effectively lowered blood glucose levels in db/db mice. The combined treatment resulted in the greatest increase in β-cell function calculated using insulinogenic index and homeostasis model assessment of β-cell function compared to the vehicle. Additionally, the combined treatment significantly reversed the increase in p16, with a similar trend observed in p21 and p53 in the islets. Treatment increased circulating β-HB and in vitro analysis suggested the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) by β-HB in reducing senescence in the islets.</p><p><strong>Conclusion: </strong>The combined administration of enavogliflozin and acarbose significantly reduced blood glucose, improved β-cell function, and reduced senescent β-cells in db/db mice. This combination therapy holds potential as a senotherapeutic strategy for managing T2DM.</p>","PeriodicalId":11153,"journal":{"name":"Diabetes & Metabolism Journal","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}