Diabetes, Obesity & Metabolism最新文献

{"title":"Type 2 diabetes and depression via microvascular dysfunction, neurodegeneration, inflammation, advanced glycation end products (AGEs), arterial stiffness.","authors":"Indra L M Steens, Miranda T Schram, Alfons J H M Houben, Tos T J M Berendschot, Annemarie Koster, Hans Bosma, Simone J P M Eussen, Bastiaan E de Galan, Thomas T van Sloten","doi":"10.1111/dom.16527","DOIUrl":"https://doi.org/10.1111/dom.16527","url":null,"abstract":"<p><strong>Aims: </strong>Type 2 diabetes increases the risk of depression, but the mechanisms underlying this association are incompletely understood. We investigated whether microvascular dysfunction, neurodegeneration, low-grade inflammation, advanced glycation end products (AGEs) and arterial stiffness, pathologies that are more common in diabetes, explain, or mediate the association between type 2 diabetes and incident clinically relevant depressive symptoms.</p><p><strong>Materials and methods: </strong>We used prospective data from The Maastricht Study, a population-based cohort study. Diabetes status and potential mediators were assessed at baseline. Clinically relevant depressive symptoms (PHQ-9 score ≥10) were assessed at baseline and each year during a median of 8.1 (IQR 4.2, 10.1) years of follow-up. Mediation analysis was employed to investigate the mediating effect of microvascular dysfunction (retinal, blood and MRI biomarkers), neurodegeneration (retina and MRI biomarkers), low-grade inflammation (blood biomarkers), AGEs (skin and blood biomarkers) and arterial stiffness (tonometry and ultrasound biomarkers).</p><p><strong>Results: </strong>Data of 6091 participants (age, 59.4 years [SD 8.6]; 51.3% women; 23.6% type 2 diabetes) were available. Type 2 diabetes was associated with a higher incidence of clinically relevant depressive symptoms (HR:1.37; 95% CI 1.13, 1.65). This association was partly mediated by microvascular dysfunction (proportion mediated:10.4% [95% CI:3.6%, 17.2%]); neurodegeneration (proportion mediated:12.1% [95% CI: 3.9%, 20.3%]); AGEs (proportion mediated:5.4% [95% CI: 3.0%, 8.8%]); and arterial stiffness (proportion mediated:8.4% [95% CI: 3.3%, 13.5%]); but not by low-grade inflammation.</p><p><strong>Conclusions: </strong>The association between type 2 diabetes and a higher risk of clinically relevant depressive symptoms is partly mediated by microvascular dysfunction, neurodegeneration, AGEs and arterial stiffness.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323976","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":"Indirect comparative efficacy and safety of tirzepatide 10 and 15 mg versus semaglutide 2.4 mg for the management of obesity and overweight in patients with type 2 diabetes.","authors":"Andreea Ciudin, Erin Johansson, Sarah Zimner-Rapuch, Georgios K Dimitriadis, Marine Bertrand, Tristan Curteis, Laura J Clark, Ludi Fan, Helene Sapin, Jean-Francois Bergmann","doi":"10.1111/dom.16508","DOIUrl":"10.1111/dom.16508","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Aims: &lt;/strong&gt;This indirect treatment comparison (ITC) compared the efficacy and safety of tirzepatide with semaglutide for managing obesity or overweight in participants with type 2 diabetes (T2D), informed by the pivotal trials SURMOUNT-2 and STEP 2.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Materials and methods: &lt;/strong&gt;Participants had body mass index (BMI) ≥ 27 kg/m&lt;sup&gt;2&lt;/sup&gt;, with ≥1 unsuccessful prior dietary weight reduction effort and glycated haemoglobin (HbA1c) 7%-10% on stable therapy. A heterogeneity assessment confirmed that study and patient baseline characteristics were similar. Bucher ITCs compared tirzepatide 10 and 15 mg once-weekly (QW) to semaglutide 2.4 mg QW via placebo, all adjunct to a reduced-calorie diet and increased physical activity.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Tirzepatide 10 and 15 mg were associated with statistically significant greater reductions in weight, BMI and HbA1c versus semaglutide. Tirzepatide 15 mg was associated with statistically significant greater odds versus semaglutide of ≥5% and ≥15% weight reduction and statistically significant improvements in several cardiometabolic risk factors, including waist circumference, fasting plasma glucose and triglycerides. Both tirzepatide doses showed non-significant trends of greater improvements in high-density lipoprotein, low-density lipoprotein, systolic blood pressure and diastolic blood pressure versus semaglutide as well as a generally comparable safety profile to semaglutide.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;In this ITC versus semaglutide 2.4 mg, tirzepatide 10 and 15 mg were associated with statistically significant greater weight, BMI and HbA1c reduction and tirzepatide 15 mg with statistically significant improvements in multiple cardiometabolic risk factors crucial in managing obesity or overweight among patients with T2D. Both tirzepatide doses also had a generally similar safety profile to semaglutide.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Plain language summary: &lt;/strong&gt;What is the context and purpose of this research study? Excess weight and type 2 diabetes (T2D) are strongly connected, where most patients with T2D have obesity or overweight. Weight management is crucial for improving T2D outcomes and preventing its progression. Weight management comprises behavioural interventions, psychological support, dietary changes and physical activity programmes. Medications may also be prescribed or surgical options may also be considered. Two such medications for weight management are tirzepatide (up to 15 mg) and semaglutide (up to 2.4 mg), which are injected subcutaneously once per week to help control appetite by prolonging patients' feeling of fullness. These medications are also used at different doses to treat T2D. Because there were no clinical trials directly comparing tirzepatide and semaglutide, particularly in patients with both T2D and either obesity or overweight, this study aimed to indirectly compare the effectiveness and safety of tirzepatide and semaglutide for wei","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332203","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":"Association between retinal microvasculature and cerebral small vessel function in type 2 diabetes: An ultrahigh field MRI study.","authors":"Jan F de Leijer, Stanley D T Pham, Tessa A C M Vissers, Lieza G Exalto, Reinier O Schlingemann, Jeroen S W Siero, Jaco J M Zwanenburg, Rafael Simó, Noemi Lois, Thomas T van Sloten, Geert Jan Biessels","doi":"10.1111/dom.16546","DOIUrl":"10.1111/dom.16546","url":null,"abstract":"","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332200","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":"Socio-demographic and clinical factors associated with the receipt of anti-obesity medication prescriptions and metabolic and bariatric surgery among eligible all of Us participants.","authors":"Olajide A Adekunle, Phuc Le, Dev Yash Gupta, Michael B Rothberg, Ha T Tran, Yihua Yue, Hamlet Gasoyan","doi":"10.1111/dom.16544","DOIUrl":"10.1111/dom.16544","url":null,"abstract":"<p><strong>Aims: </strong>There is a paucity of data on socio-economic characteristics associated with the use of anti-obesity medications (AOM) and metabolic and bariatric surgery (MBS) when accounting for clinical factors. This study characterized factors associated with the receipt of AOM prescriptions and MBS.</p><p><strong>Materials and methods: </strong>A cross-sectional study was conducted using the All of Us (AoU) Research (v.8) data. Patients with obesity who received AOM or MBS between 2017 and 2023 were included. Descriptive statistics were used to summarize patient characteristics, while multivariable regression examined factors associated with the receipt of the treatments.</p><p><strong>Results: </strong>Only 6.6% of 183 424 patients for AOM analysis, received an AOM prescription, while 1.8% underwent MBS among 93 146 patients. Being a man (vs. woman, adjusted odds ratio [aOR] = 0.62, 95% confidence interval [CI], 0.59-0.65), Medicare insurance holder (vs. private, aOR = 0.78, 95% CI, 0.72-0.84), retiree (vs. employed, aOR = 0.70, 95% CI, 0.66-0.75) and high school degree holders (vs. college, aOR = 0.85, 95% CI, 0.80-0.90) were associated with lower odds of receiving AOM. Being single (vs. married, aOR = 0.84, 95% CI, 0.74-0.96), retired (vs. employed, aOR = 0.63, 95% CI, 0.49-0.80), with body mass index (BMI) 35- < 40 (vs. ≥45, aOR = 0.13, 95% CI, 0.11-0.15) were associated with lower odds of MBS. Patients with dyslipidaemia and obstructive sleep apnoea had higher odds of receiving both treatments.</p><p><strong>Conclusions: </strong>Disparities in obesity treatment exist. Male sex, older age, lower income and lower BMI were associated with lower odds of treatment, while dyslipidaemia and obstructive sleep apnoea were associated with higher odds.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332205","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":"The Changing Epidemiology of Type 1 Diabetes: A Global Perspective.","authors":"Kirstine J Bell, Samantha J Lain","doi":"10.1111/dom.16501","DOIUrl":"https://doi.org/10.1111/dom.16501","url":null,"abstract":"&lt;p&gt;&lt;p&gt;The prevalence of type 1 diabetes is increasing, with significant implications for public health systems worldwide. This review provides a global overview of the current epidemiology of type 1 diabetes, examining the trends, risk factors, and regional variations in incidence. We explore the influence of genetic, environmental, and socio-economic factors on the rising incidence of type 1 diabetes. The review also highlights temporal trends in the management of type 1 diabetes and the risk of mortality and morbidity from acute and long-term complications, including hypoglycaemia, diabetic ketoacidosis, and retinopathy. By synthesizing global and regional data, we aim to provide valuable insights for local health service planning, disease prediction, and tailored interventions. This article underscores the importance of continued research into the epidemiology of type 1 diabetes to better inform prevention, treatment, and management strategies of this growing global health challenge. Plain Language Summary Type 1 diabetes (T1D) is an autoimmune condition that begins silently, with the body attacking insulin-producing cells in the pancreas. This process occurs in two early, silent stages, detectable through blood tests for antibodies, before symptoms appear. It eventually progresses to stage 3, when symptoms develop and insulin treatment becomes necessary. Prevalence T1D affects about 9 million people globally, including over 1.5 million children. In addition to those with symptoms, many children and adults may unknowingly have early stage T1D. These can be detected through screening and are estimated to affect around 0.3% of the population. Incidence In 2024, there were over 500,000 new diagnoses of T1D worldwide, with cases increasing each year. Rates vary by region, age, and sex. Most diagnoses occur in childhood or early adulthood, with a peak around puberty, though it can develop later in life. Rates are highest in high-income countries such as Finland and Australia. Lower rates in other regions may reflect limited surveillance. Some countries have reported fluctuating trends, possibly linked to infections. Improved awareness and diagnostics explain and changing risk factors may also play a role. Risk Factors The risk of T1D is impacted by genetic, demographic, and environmental factors. Family history increases risk, though the majority of people diagnosed don't have a family history. Genetic risk scores can also help identify children at higher risk. Risk changes with age, early signs often appear before age 3, and younger children tend to progress more quickly. Two childhood diagnosis peaks occur at ages 4-7 years and 10-14 years. Researchers are exploring possible subtypes of T1D based on age and disease behaviour. White European populations have the highest rates, but increases are also seen in other groups. Environmental factors like viral infections, caesarean birth, and early diet are being studied. Complications Managing T1D is co","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323975","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":"Gestational diabetes risk associated with early pregnancy blood pressure characteristics and trajectories: A Chinese prospective cohort study.","authors":"Weigui Ni, Zhijian Chen, Minting Zhu, Yunyi Li, Lijuan Lai, Bingyi Lin, Zhongai Ouyang, Long Jiang, Yi Jing, Jingjie Fan","doi":"10.1111/dom.16555","DOIUrl":"10.1111/dom.16555","url":null,"abstract":"<p><strong>Background: </strong>Limited evidence exists regarding early pregnancy pulse pressure (PP) and blood pressure (BP) trajectories in gestational diabetes mellitus (GDM) development. Understanding these associations may provide valuable insights for early interventions to mitigate the risk of GDM.</p><p><strong>Methods: </strong>Included were 16 020 pregnant women from the Shenzhen Maternity and Child Healthcare Hospital. Early pregnancy BP characteristics were determined based on BP measurements recorded at the initial prenatal visit, including systolic blood pressure (SBP), diastolic blood pressure (DBP), and PP. Early pregnancy SBP trajectories up to 20 weeks' gestation were identified using latent class growth mixture models (LCGM) based on multiple prenatal visits. Multivariate logistic regression analyses were performed to assess the association between early pregnancy BP characteristics and SBP trajectories with the risk of GDM.</p><p><strong>Results: </strong>Among participants, 23.91% (3830/16 020) developed GDM. Moderate BP (SBP 120-139 mmHg and/or DBP 80-89 mmHg) was associated with elevated GDM risk (OR = 1.24, 95% CI 1.14-1.35), with isolated moderate SBP (120-139 mmHg) demonstrating a stronger association (OR = 1.27, 95% CI 1.16-1.38), while early pregnancy hypertension conferred an additional 32% risk elevation (OR = 1.32, 95% CI 1.02-1.71). Linear associations were observed for SBP (each 10 mmHg increase: OR = 1.14, 95% CI 1.10-1.18), DBP (each 5 mmHg: OR = 1.07, 1.05-1.09), and PP (each 5 mmHg: OR = 1.04, 1.02-1.07) with GDM risk. The highest PP tertile demonstrated a 20% elevated risk versus the lowest (OR = 1.20, 1.09-1.32). Trajectory analysis revealed four distinct SBP patterns, with escalating risks: medium-stable (OR = 1.31), medium-high stable (OR = 1.61), and peak pattern (OR = 1.98) compared with low-stable reference (all p < 0.01).</p><p><strong>Conclusions: </strong>Poor early pregnancy BP characteristics and unfavourable BP trajectories are associated with an elevated risk of GDM. These findings suggest that monitoring BP throughout early pregnancy could serve as an essential strategy for identifying women at higher risk for GDM, potentially enabling timely preventative measures.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332202","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":"Oxidative stress, senescence and mRNA decay in peripheral blood mononuclear cells of women with gestational diabetes mellitus-link to increased cardiovascular disease risk.","authors":"Tove Lekva, Marie Cecilie Paasche Roland, Elisabeth Qvigstad, Yusuf Khan, Kristin Godang, Annika E Michelsen, Thor Ueland","doi":"10.1111/dom.16521","DOIUrl":"https://doi.org/10.1111/dom.16521","url":null,"abstract":"<p><strong>Aims: </strong>Women who develop gestational diabetes mellitus (GDM) have a pancreatic β-cell defect that cannot compensate for the insulin resistance of pregnancy. The glucose intolerance may, in addition to direct effects, negatively impact lipid metabolism, promote vascular dysfunction and contribute to cardiovascular disease (CVD). We assessed associations between oxidative stress and senescence markers with indices of glucose and lipid metabolism in women developing GDM and with CVD risk after 5 years.</p><p><strong>Materials and methods: </strong>The oxidative stress and senescence markers NRF2, GPX4, TERC, XRN1 and DCP2 were assessed in peripheral blood mononuclear cells (PBMCs), advanced oxidation protein products (AOPP) and β-galactosidase in plasma, from healthy (n = 253) and women with GDM (n = 31) during pregnancy and at 5-year follow-up, from the STORK study. We investigated their associations with established markers of disease activity and later CVD.</p><p><strong>Results: </strong>Plasma AOPP and β-galactosidase were increased early in pregnancy in women developing GDM later and associated with indices of glucose metabolism and TG/HDL-Cholesterol. RNA levels of transcripts involved in telomer maintenance and antioxidant responses were decreased in women with GDM during pregnancy and at follow-up. DCP2 and XRN1 expression were positively associated with β-cell function at all timepoints and with pulse wave velocity at 5-year follow-up in women with previous GDM.</p><p><strong>Conclusions: </strong>Markers of vascular oxidative stress and senescence are increased and correlate with indices of glucose and lipid metabolism early in pregnancy in women developing GDM. Cellular markers reflecting attenuated defence against oxidative stress and senescence decrease throughout pregnancy and at 5-year follow-up and correlate with aortic stiffness in women with previous GDM.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315661","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":"Trajectories of body mass index and diabetes mellitus risk among elderly Chinese adults: A 10-year longitudinal study.","authors":"Yan Guo, Xiaoyu Zhang, Wei Li, Yaxuan Zhou, Yuqian Zhang, Mei Yang","doi":"10.1111/dom.16530","DOIUrl":"https://doi.org/10.1111/dom.16530","url":null,"abstract":"<p><strong>Aims: </strong>This study aimed to identify trajectories of body mass index (BMI) for elderly Chinese adults, evaluate the impact of BMI trajectories on the risk of diabetes mellitus (DM) or impaired fasting glucose (IFG) among normoglycaemic elderly and compare the incidence of progression to DM and reversion to normoglycaemia between BMI trajectories among IFG elderly to prevent the occurrence of diabetes.</p><p><strong>Materials and methods: </strong>This study included 148 970 participants. Group-based trajectory modelling was used to identify BMI trajectories. Cox proportional hazards regression models were used to examine the associations between BMI trajectories and the incidence of DM, IFG and reversion to normoglycaemia.</p><p><strong>Results: </strong>A total of six patterns of trajectory were identified: minor decrease, sharply decrease, stable, slight increase, moderate increase and significant increase among 148 970 elderly Chinese adults. For normoglycaemic elderly, compared with normal weight-stable trajectory, the trajectories with higher DM risk are the obese-pronounced decrease group, the obese-marginal increase group, and the obese-minor decrease group. The adjusted hazard ratios (HRs) were: 2.70 (95% confidence interval [CI]: 2.35, 3.11), 2.55 (95% CI: 2.28, 2.86) and 2.41 (95% CI: 2.24, 2.60), respectively. The trajectories with higher IFG risk are the obese-marginal increase group, the obese-minor decrease group and the overweight-moderate increase group, with adjusted HRs of 2.26 (95% CI: 2.08, 2.45), 1.96 (95% CI: 1.86, 2.07) and 1.91 (95% CI: 1.79, 2.04), respectively.</p><p><strong>Conclusions: </strong>Among 148 970 participants, normoglycaemic elderly with increased BMI trajectories showed elevated DM and IFG risks in groups with underweight and normal weight. Regardless of the BMI trajectory, the risk of DM was increased in both the obese and overweight groups. For IFG elderly, the highest DM incidence was presented in the decreasing trajectories.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315662","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":"AdipoRon attenuates steatosis, inflammation and fibrosis in murine diet-induced NASH via inhibiting ER stress.","authors":"Lulin Nie, Kaiwu He, Wei Wu, Huan Zhang, Chuanyue Gao, Bocheng Xiong, Shangming Li, Yongmei Xie, Haihui Xie, Xifei Yang","doi":"10.1111/dom.16542","DOIUrl":"https://doi.org/10.1111/dom.16542","url":null,"abstract":"<p><strong>Aim: </strong>The rising global prevalence of obesity has accelerated the incidence of metabolic dysfunction-associated steatotic liver disease (MASLD), with nonalcoholic steatohepatitis (NASH) representing its progressive and life-threatening phenotype. Despite its clinical urgency, no pharmacotherapy is currently approved for NASH. AdipoRon, an orally active adiponectin receptor agonist, exhibits dual regulatory effects on glucose/lipid homeostasis alongside anti-inflammatory and antioxidant properties. However, its therapeutic potential in metabolic stress-driven NASH remains underexplored. This study elucidates the efficacy and molecular mechanisms of AdipoRon in mitigating metabolic stress-induced NASH.</p><p><strong>Materials and methods: </strong>We employed a multi-modal approach combining in vitro and in vivo models: palmitic acid (PA)-challenged alpha mouse liver 12 (AML12) hepatocytes and mice fed a Western diet (WD) or a methionine-choline-deficient (MCD) diet. Proteomic profiling integrated with bioinformatics analysis was utilized to dissect AdipoRon's mechanism. Pharmacological validation via endoplasmic reticulum (ER) stress modulation (e.g., cinchonine) further clarified pathway specificity.</p><p><strong>Results: </strong>In vitro, AdipoRon attenuated PA-induced lipid accumulation and inflammatory cytokine release in hepatocytes. In vivo, AdipoRon administration markedly reduced hepatic injury, steatosis, lobular inflammation and collagen deposition in diet-induced NASH mice. Mechanistically, proteomic analysis identified ER stress suppression as a central pathway, with rescue experiments confirming that cinchonine (an ER stress activator) abrogated AdipoRon's hepatoprotection.</p><p><strong>Conclusions: </strong>Our findings establish AdipoRon as a potent inhibitor of ER stress, effectively counteracting metabolic stress-induced NASH pathogenesis. These results highlight its translational promise as a targeted therapy for NASH, addressing critical unmet clinical needs.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315659","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":"Efficacy and safety of a tubeless open-source hybrid automated insulin delivery use at home among adults with type 1 diabetes mellitus: Results from a 26-week, free-living, randomized crossover trial.","authors":"Mengyun Lei, Ping Ling, Beisi Lin, Jing Lv, Zhigu Liu, Yongwen Zhou, Hongrong Deng, Daizhi Yang, Chaofan Wang, Xubin Yang, Jinhua Yan, Wen Xu","doi":"10.1111/dom.16505","DOIUrl":"https://doi.org/10.1111/dom.16505","url":null,"abstract":"<p><strong>Aim: </strong>This study aims to evaluate the efficacy and safety of a tubeless open-source hybrid automated insulin delivery (OS-AID) in managing adults with type 1 diabetes mellitus (T1DM) in China, where commercial AID systems are not accessible.</p><p><strong>Methods: </strong>In this open-label randomized crossover study, adults with T1DM aged 18-75 years, glycated haemoglobin (HbA1c) 7%-11% (53-97 mmol/mol) and who have never used AID previously, were assigned to either Android-version hybrid OS-AID (AAPS) or sensor-augmented insulin pump (SAP) therapy for three months, followed by a crossover to the alternative treatment for an additional three months. The primary endpoint was the percentage of time in range (TIR, 70-180 mg/dL [3.9-10.0 mmol/L]) during the final two weeks of each treatment phase.</p><p><strong>Results: </strong>A total of 28 adults with T1DM, with a mean age of 33.6 ± 10.4 years and a T1DM duration of 12.6 ± 7.0 years, were enrolled in this study. The percentage of TIR (70-180 mg/dL [3.9-10.0 mmol/L]) during the AAPS phase was 75.6 ± 10.3%, significantly higher than the 60.4 ± 15.1% observed during the SAP phase (p < 0.01). AAPS was notably more effective in managing nocturnal glucose levels compared to diurnal glucose levels (80.9 ± 13.6% vs. 73.8 ± 10.2%, p < 0.01). No significant differences in time below range were observed between the two phases. No severe hypoglycaemia or serious adverse events occurred in either treatment phase.</p><p><strong>Conclusion: </strong>In this 26-week trial involving adults with T1DM who had never previously used AID, the tubeless AAPS use at home resulted in a significantly higher percentage of time in the target glucose range without increasing hypoglycaemia risk compared to SAP therapy.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315660","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}