Diabetes, Obesity & Metabolism最新文献

{"title":"Effects of antidiabetic agents on lipid metabolism of skeletal muscle: A narrative review.","authors":"Ming Xu, Dongqing Lv, Hongxia Wei, Zhe Li, Shuqing Jin, Qinhao Liu, Yi Zhang, Yunfeng Liu","doi":"10.1111/dom.16189","DOIUrl":"https://doi.org/10.1111/dom.16189","url":null,"abstract":"<p><p>Metabolic syndrome-related diseases frequently involve disturbances in skeletal muscle lipid metabolism. The accumulation of lipid metabolites, lipid-induced mitochondrial stress in skeletal muscle cells, as well as the inflammation of adjacent adipose tissue, are associated with the development of insulin resistance and metabolic dysfunction. Consequently, when antidiabetic medications are used to treat various chronic conditions related to hyperglycaemia, the impact on skeletal muscle lipid metabolism should not be overlooked. However, current research has predominantly focused on muscle mass rather than skeletal muscle lipid metabolism and its interplay with glucose metabolism. In this review, we summarised the latest research on the effects of antidiabetic drugs and certain natural compounds with antidiabetic activity on skeletal muscle lipid metabolism, focusing on data from preclinical to clinical studies. Given the widespread use of antidiabetic drugs, a better understanding of their effects on skeletal muscle lipid metabolism merits further attention in future research.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977034","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":"Effect of insulin sensitivity, insulin secretion, and beta cell function on the remission of type 2 diabetes: A post hoc analysis of the IDEATE trial.","authors":"Xianglin Wu, Qiuyue Huang, Yi Ding, Qiuyu Cao, Youjin Jiang, Yu Xu, Zhiyun Zhao, Min Xu, Jieli Lu, Tiange Wang, Guang Ning, Weiqing Wang, Yufang Bi, Yuchen Xu, Mian Li","doi":"10.1111/dom.16180","DOIUrl":"https://doi.org/10.1111/dom.16180","url":null,"abstract":"<p><strong>Aims: </strong>To compare the probability of achieving diabetes remission in individuals with different phenotypes of insulin sensitivity, insulin secretion, and beta cell function and further detect the effects of diet, exercise, and lifestyle education intervention on these indexes.</p><p><strong>Methods: </strong>Three-hundred and one participants who had glycated haemoglobin (HbA1c) data at baseline and after intervention were included for this post hoc analysis. We used the multi-way analysis of variance to assess the differences between the diabetes remission and non-remission groups or between intervention groups in changes of the indexes of insulin sensitivity, insulin secretion, and beta cell function. Furthermore, logistic regression analysis was used to identify the association between the diabetes remission and baseline and change of each insulin index.</p><p><strong>Results: </strong>Participants with a higher disposition index (DI) or higher adaptation index at baseline were more likely to achieve diabetes remission. The diabetes remission group had a significantly greater increase in AUC_c-pep0-30/AUC_gluc0-30, DI, and adaptation index compared with the non-remission group, while there were no between-group differences in indexes of insulin sensitivity. Participants with greater increases in insulin secretion and beta cell function were more likely to achieve diabetes remission. Indexes of beta cell function improved in all intervention groups, while the diet intervention induced significant improvement compared with lifestyle education.</p><p><strong>Conclusions: </strong>These findings supported the importance of aggressively implementing intensive lifestyle interventions for individuals with type 2 diabetes at an early stage of the disease, when beta cell function was not yet significantly impaired, to promote achieving diabetes remission.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977033","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":"Chemerin loss-of-function attenuates glucagon-like peptide-1 secretion in exercised obese mice.","authors":"Qilong Zhang, Yi Jia, Yifan Guo, Xiaohan Yu, Ru Wang, Xiaohui Wang","doi":"10.1111/dom.16126","DOIUrl":"https://doi.org/10.1111/dom.16126","url":null,"abstract":"<p><strong>Aims: </strong>To investigate the role of chemerin reduction in mediating exercise-induced Glucagon-like peptide-1 (GLP-1) secretion and the amelioration of pancreatic β-cell function in obesity.</p><p><strong>Materials and methods: </strong>Obesity models were established using wild-type and chemerin systemic knockout mice, followed by 8 weeks of moderate-intensity continuous aerobic exercise training. Serum chemerin levels, GLP-1 synthesis, glucose tolerance, pancreatic β-cell function, structure, and apoptosis were assessed. In vitro experiments were conducted on STC-1 cells, derived from murine intestinal endocrine cells, to evaluate GLP-1 secretion following exogenous chemerin treatment. Additionally, colonic tissue inflammation and apoptosis were analyzed using qPCR and TUNEL staining.</p><p><strong>Results: </strong>In obese wild-type mice, moderate-intensity aerobic exercise significantly reduced serum chemerin levels, enhanced GLP-1 secretion, and improved glucose tolerance, pancreatic β-cell structure, function, and apoptosis. These effects were absent in obese chemerin knockout mice. Exogenous chemerin treatment reduced GLP-1 secretion in STC-1 cells. Furthermore, the beneficial effects of exercise on colonic inflammation and apoptosis observed in wild-type mice were abolished in chemerin knockout mice.</p><p><strong>Conclusion: </strong>Reduction of chemerin is crucial for the beneficial effects of aerobic exercise on GLP-1 secretion and pancreatic β-cell function in obesity. The mechanisms behind these effects may involve improvements in colonic inflammation and apoptosis. These findings offer new insights into the molecular mechanisms through which exercise improves obesity-related metabolic dysfunction.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968953","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":"Risk of insulin initiation with sodium-glucose cotransporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes mellitus: A real-world claims database study in Japan.","authors":"Ryo Suzuki, Shingo Shoji, Yoko Yoshinaga, Yoshinori Kosakai, Mami Shintani-Tachi","doi":"10.1111/dom.16188","DOIUrl":"https://doi.org/10.1111/dom.16188","url":null,"abstract":"<p><strong>Aims: </strong>Insulin therapy is a cornerstone in type 2 diabetes mellitus (T2DM) management, but its use is associated with several barriers, including hypoglycaemia, fear of injections and high costs. We compared the risk of insulin initiation and other treatment intensification between patients with T2DM newly treated with a sodium-glucose cotransporter-2 inhibitor (SGLT2i) versus those newly treated with a dipeptidyl peptidase-4 inhibitor (DPP4i).</p><p><strong>Materials and methods: </strong>This Japanese retrospective cohort study was conducted between 1 January 2015 and 31 March 2023 using the JMDC Claims Database. Patients with T2DM newly treated with an SGLT2i or a DPP4i were matched 1:1 using propensity score (n = 18 488 each). Incidence rates (IR) of insulin initiation, other antidiabetic drugs (OAD) and antihypertensive drugs added onto baseline treatment were calculated for each treatment group. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using a Cox proportional hazards model.</p><p><strong>Results: </strong>The IR of insulin initiation was 0.95 and 2.12 per 1000 person-years in the SGLT2i and DPP4i groups, respectively, with significantly lower risk in the SGLT2i group than in the DPP4i group (HR 0.46, 95% CI: 0.28-0.74, p = 0.001). The risks of OAD (HR 0.66, 95% CI: 0.64-0.69, p < 0.001) and antihypertensive drugs (HR 0.90, 95% CI: 0.85-0.95, p < 0.001) added onto baseline treatment were lower in the SGLT2i group than in the DPP4i group.</p><p><strong>Conclusions: </strong>The risk of insulin initiation was lower in patients with T2DM newly treated with an SGLT2i than in those newly treated with a DPP4i. SGLT2i may reduce or delay the need for insulin therapy.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977037","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":"Effects of the SGLT2 inhibitor ipragliflozin and metformin on hepatic steatosis and liver fibrosis: Sub-analysis of a randomized controlled study.","authors":"Kiichi Hirayama, Masaya Koshizaka, Ryoichi Ishibashi, Mayumi Shoji, Takuro Horikoshi, Kenichi Sakurai, Koutaro Yokote","doi":"10.1111/dom.16198","DOIUrl":"https://doi.org/10.1111/dom.16198","url":null,"abstract":"<p><strong>Aims: </strong>To compare the effects of ipragliflozin, a sodium-dependent glucose transporter-2 inhibitor, and those of metformin on the visceral fat area (VFA), a prospective, multi-centre, open-label, blinded-endpoint, randomized, controlled study was undertaken. The generated data were used to examine the effects of ipragliflozin and metformin on indices of hepatic steatosis and liver fibrosis.</p><p><strong>Materials and methods: </strong>In total, 103 Japanese patients with type-2 diabetes (T2D), body mass index (BMI) of ≥22 kg/m² and glycated haemoglobin level of 7%-10% were randomly administered ipragliflozin 50 mg or metformin 1000 mg for 24 weeks. Various parameters, including hepatic steatosis indices, fatty liver index (FLI), hepatic steatosis index (HSI), non-alcoholic fatty liver disease-liver fat score (NAFLD-LFS), liver fibrosis indices, AST to platelet ratio index (APRI) and fibrosis-4 (FIB-4) index, were compared in the sub-analyses. The correlations between changes in each index and VFA were evaluated.</p><p><strong>Results: </strong>At baseline, patients demonstrated moderate hepatic steatosis, with FLI scores of 52.9 ± 26.6 and 57.8 ± 29.0 in the ipragliflozin and metformin groups, respectively. At 24 weeks, compared with metformin, ipragliflozin showed improvements in hepatic steatosis indices: FLI (-9.24 ± 10.7 vs. -3.45 ± 11.8, p = 0.013), HSI (-1.45 ± 2.32 vs. -0.45 ± 1.87, p = 0.021), NAFLD-LFS (-0.70 ± 1.46 vs. -0.04 ± 0.98, p = 0.011) and liver fibrosis index: APRI (-0.110 ± 0.323 vs. 0.033 ± 0.181, p = 0.010). In the ipragliflozin group, changes in FLI and HSI were correlated with VFA reduction (r = 0.340, p = 0.024; r = 0.367, p = 0.011, respectively).</p><p><strong>Conclusions: </strong>Compared with metformin, ipragliflozin improved multiple hepatic steatosis and liver fibrosis indices, suggesting that ipragliflozin exerts potential hepatoprotective effects in early-stage liver disease associated with T2D.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977035","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":"Long-term blood glucose control via glucose-activated transcriptional regulation of insulin analogue in type 1 diabetes mice.","authors":"Wanling Lu, Lifang Xie, Yanhan Zhang, Hong Gao, David Geng, Chunguang Xie, Ming Liu, Gang Wang","doi":"10.1111/dom.16197","DOIUrl":"https://doi.org/10.1111/dom.16197","url":null,"abstract":"<p><strong>Aim: </strong>To achieve glucose-activated transcriptional regulation of insulin analogue in skeletal muscle of T1D mice, thereby controlling blood glucose levels and preventing or mitigating diabetes-related complications.</p><p><strong>Materials and methods: </strong>We developed the GANIT (Glucose-Activated NFAT-regulated INSA-F Transcription) system, an innovative platform building upon the previously established intramuscular plasmid DNA (pDNA) delivery and expression system. In the GANIT system, skeletal muscle cells are genetically engineered to endogenously produce the insulin analogue INSA-F (Insulin Aspart with Furin cleavage sites). The transcription of INSA-F is precisely controlled by a glucose-responsive promoter containing NFAT (Nuclear Factor of Activated T-cells) regulatory motifs, which can be activated in response to changes in extracellular glucose concentrations. This design enables glucose-dependent regulation of insulin analogue expression, mimicking physiological glucose-responsive insulin secretion.</p><p><strong>Results: </strong>T1D mice that received two GANIT treatments over a 2-month experimental period demonstrated significant improvements in glucose homeostasis, glucose tolerance and glycated haemoglobin (HbA1c) levels. Additionally, the treatment effectively reduced oxidative stress and alleviated cardiac and renal fibrosis, while maintaining a favourable biosafety profile.</p><p><strong>Conclusion: </strong>The GANIT system provides significant advantages in terms of efficiency, convenience and cost-effectiveness, making it a promising approach for regulating blood glucose levels and alleviating diabetes-related complications in insulin-deficient diabetes.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977036","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":"Correction to \"Long-term safety and efficacy of glucagon-like peptide-1 receptor agonists in individuals with obesity and without type 2 diabetes: A global retrospective cohort study\".","authors":"","doi":"10.1111/dom.16204","DOIUrl":"https://doi.org/10.1111/dom.16204","url":null,"abstract":"","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968955","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":"Unexpected cardiovascular risks of glucagon-like peptide-1 receptor agonist and aspirin co-administration in individuals with obesity, with and without type 2 diabetes: A propensity score matched cohort study.","authors":"Chia-Ming Lin, Jo-Ching Chen, Gideon Meyerowitz-Katz, Yu-Nan Huang, Pen-Hua Su","doi":"10.1111/dom.16191","DOIUrl":"https://doi.org/10.1111/dom.16191","url":null,"abstract":"<p><strong>Aims: </strong>To examine the cardiovascular safety of combining glucagon-like peptide-1 receptor agonists (GLP-1 RAs) with aspirin in individuals with obesity, both with and without type 2 diabetes (T2D).</p><p><strong>Materials and methods: </strong>This propensity score matched cohort study analysed data from 2 946 579 individuals with obesity, with and without T2D, using the TriNetX US and Global dataset. Participants were categorized into four matched groups: those receiving GLP-1 RA plus aspirin versus those receiving GLP-1 RA alone, for both diabetic and non-diabetic individuals. Cardiovascular outcomes and adverse events were evaluated over 5 years using Cox proportional hazards models.</p><p><strong>Results: </strong>Individuals with obesity treated with GLP-1 RAs plus aspirin showed significantly higher risks of various cardiovascular events compared to those on GLP-1 RAs alone. In non-diabetic obese individuals, the combination therapy increased risks of hypertensive heart diseases (HR 1.40, 95% CI 1.15-1.60), ischaemic heart disease (HR 2.39, 95% CI 1.92-2.97) and heart failure (HR 1.97, 95% CI 1.54-2.53). Similar patterns were observed in individuals with T2D. Atrial fibrillation and cardiac arrhythmias showed increasing hazard ratios over time. The combination therapy also led to more frequent adverse events, including gastrointestinal bleeding.</p><p><strong>Conclusions: </strong>The combination of GLP-1 RAs with aspirin in individuals with obesity, both with and without T2D, was associated with increased cardiovascular risks compared to GLP-1 RA monotherapy. These findings suggest that there may be risks associated with the combined use of these treatments and highlight the need for further research into this possible complication with regard to treatment.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977039","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":"Trends and analysis of risk factor differences in the global burden of chronic kidney disease due to type 2 diabetes from 1990 to 2021: A population-based study.","authors":"Yifei Wang, Ting Lin, Jiale Lu, Wenfang He, Hongbo Chen, Tiancai Wen, Juan Jin, Qiang He","doi":"10.1111/dom.16183","DOIUrl":"https://doi.org/10.1111/dom.16183","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Chronic kidney disease (CKD) is a significant contributor to the global burden of disease. Among its causes, chronic kidney disease due to type 2 diabetes (CKD-T2D) is the primary subtype. This study aims to provide an updated assessment of the global disease burden of CKD-T2D from 1990 to 2021. It will analyse the trends in the global burden of CKD-T2D and the differences in risk factors, as well as project changes over the next 15 years.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The data for this study were derived from the Global Burden of Disease, Injuries, and Risk Factors Study (GBD) 2021. Estimates of prevalence, incidence, deaths and disability-adjusted life years (DALYs) for CKD-T2D, along with their 95% uncertainty intervals (UIs), were extracted. The trends in CKD-T2D burden from 1990 to 2021 were analysed from overall and local perspectives. An age-period-cohort model was used to estimate the age, period and cohort effects on the prevalence and incidence of CKD-T2D between 1990 and 2021. A decomposition analysis was conducted to assess the contribution of population size, age structure and epidemiological changes to the burden of CKD-T2D. Population-attributable fractions were determined for each risk factor, and a difference analysis was conducted. Additionally, projections were made regarding changes in the burden of CKD-T2D over the next 15 years.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In 2021, the global burden of CKD-T2D remained significant, with a total of 107 559 955 cases. The age-standardized prevalence rate (ASPR) was 1259.63 per 100 000 people. The age-standardized incidence rate (ASIR) was 23.07 per 100 000 people, and the age-standardized death rate (ASDR) was 5.72 per 100 000 people. The age-standardized disability-adjusted life years (DALYs) was 131.08 per 100 000. The global burden of CKD-T2D showed variation across different socio-demographic index (SDI) regions. In 2021, the overall burden of CKD-T2D continued to rise, with the age effect increasing with age. Both prevalence and incidence risks showed an upward trend over time. Decomposition analysis indicated that population growth and ageing were the primary contributors to the global burden of DALYs related to CKD-T2D. Metabolic risk factors such as high fasting plasma glucose and high body mass index (BMI) are the most significant attributable risk factors. It is projected that by 2036, the trends in ASPR, ASIR, ASDR and age-standardized DALYs will stabilize. However, ASIR and age-standardized DALYs are expected to continue rising, and the number of cases of prevalence, incidence, mortality and DALYs will persist in their upward trend.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;CKD-T2D imposes a significant global disease burden, with health disparities and unequal disease outcomes continuing to worsen across countries and regions due to differences in socio-economic development levels. This burden is primarily driven by population growth, ageing and meta","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977038","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":"Beta cell function and global glucose metabolism are impaired in Dp(16)1Yey mouse model of Down syndrome.","authors":"Stefania Tolu, Rim Hamzé, Manon Moreau, Romane Bertrand, Nathalie Janel, Jamileh Movassat","doi":"10.1111/dom.16155","DOIUrl":"https://doi.org/10.1111/dom.16155","url":null,"abstract":"<p><strong>Aims: </strong>Down syndrome (DS) or trisomy 21 is the most prevalent genetic disorder in the world. In addition to common symptoms such as intellectual disabilities and morphological abnormalities, several comorbidities are associated with DS, including metabolic dysfunction. Obesity and diabetes are more prevalent in people with DS compared with the general population. However, the mechanisms linking obesity/diabetes to DS remain poorly understood. Systematic investigation of metabolic disorders in animal models of DS is scarce.</p><p><strong>Materials and methods: </strong>We used the Dp(16)1Yey mouse model of DS to evaluate the energy and glucose metabolism in both male and female Dp(16)1Yey mice at 3 and 6 months of age. We assessed the whole-body glucose metabolism by glucose and insulin tolerance tests, and investigated the pancreatic functions in terms of insulin synthesis, ß cell mass and the glucose-induced insulin secretion in vivo.</p><p><strong>Results: </strong>We show that Dp(16)1Yey mice do not present signs of obesity when they are fed with chow diet. However, these mice are glucose intolerant and insulin resistant, and exhibit dysfunctions of their endocrine pancreas, reflected by decreased insulin content and defective glucose-induced insulin secretion (GIIS) in vivo. The impairment of metabolic parameters is similar between males and females trisomic mice, indicating the absence of metabolic sexual dimorphism in this model.</p><p><strong>Conclusions: </strong>Our study suggests that Dp(16)1Yey model is suitable for the assessment of metabolic disorders associated with DS.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968951","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}