Diabetes, Obesity & Metabolism最新文献

{"title":"Non-clinical and first-in-human characterization of ECC5004/AZD5004, a novel once-daily, oral small-molecule GLP-1 receptor agonist.","authors":"Amina Z Haggag, Jianfeng Xu, Laurie Butcher, Sandra Pagnussat, Graeme Davies, Sara Lundqvist, Wenyu Wang, Natalie Van Zuydam, Karin Nelander, Aruni Jha, Hongtao Yu, Alessandro Boianelli, Bosse Lindmark, Anna Ollerstam, Xuefeng Sun, Fan Wang, Xiaoliang Pan, Haihui Liu, Wengang Chen, Jianfeng Xu, Kristina Wallenius, Jingye Zhou","doi":"10.1111/dom.16047","DOIUrl":"10.1111/dom.16047","url":null,"abstract":"<p><strong>Aims: </strong>GLP-1 receptor agonists (GLP-1 RAs) are proven therapies for type 2 diabetes mellitus (T2DM) and overweight or obesity. We performed non-clinical and first-in-human (FIH) evaluation of ECC5004/AZD5004, an oral small-molecule GLP-1 RA.</p><p><strong>Materials and methods: </strong>ECC5004 was profiled in cell lines overexpressing human GLP-1R, in glucose-stimulated insulin secretion (GSIS) assays in a human β-cell line and non-human primates (NHPs). To evaluate safety, ECC5004 was orally administered to NHPs for 9 months and a phase I, double-blind, placebo-controlled FIH study was conducted. This study evaluated single doses of ECC5004 (1-300 mg) in healthy volunteers, and multiple daily doses (5, 10, 30 and 50 mg) in patients with T2DM for 28 days.</p><p><strong>Results: </strong>ECC5004 bound to the hGLP-1R (IC₅₀ = 2.4 nM) augmented cAMP signalling without β-arrestin-2 recruitment or receptor internalization. ECC5004 potentiated GSIS in both EndoC-βH5 cells (EC₅₀ = 5.9 nM) and in vivo in NHPs (EC₅₀ = 0.022 nM). Dose-dependent body weight changes compared to control were seen in the 9-month NHP toxicity study. In the first-in-human study, ECC5004 was well tolerated with no serious adverse events. Dose-dependent reductions in glucose and body weight were observed with a dose-proportional exposure at doses ≥25 mg.</p><p><strong>Conclusion: </strong>ECC5004 engaged the GLP-1R across the therapeutic dose range tested and had a safety and tolerability profile consistent with other GLP-1 RAs, along with a pharmacokinetic profile compatible with once-daily oral dosing. These data support continued development of ECC5004 as a potential therapy for T2DM and overweight or obesity.</p><p><strong>Clinical trial registration: </strong>NCT05654831.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":"551-562"},"PeriodicalIF":5.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11701199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and effects of acetylated and butyrylated high-amylose maize starch on youths recently diagnosed with type 1 diabetes: A pilot study.","authors":"Heba M Ismail, Jianyun Liu, Michael Netherland, Nur A Hasan, Carmella Evans-Molina, Linda A DiMeglio","doi":"10.1111/dom.16039","DOIUrl":"10.1111/dom.16039","url":null,"abstract":"","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":"987-992"},"PeriodicalIF":5.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520527","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":"Relationship between trajectory of Chinese visceral adiposity index and risk of type 2 diabetes mellitus: Evidence from the China-PAR project.","authors":"Xueru Fu, Yang Zhao, Yuying Wu, Liuding Wen, Weifeng Huo, Dongdong Zhang, Yanyan Zhang, Jianxin Li, Xiangfeng Lu, Fulan Hu, Ming Zhang, Dongsheng Hu","doi":"10.1111/dom.16074","DOIUrl":"10.1111/dom.16074","url":null,"abstract":"<p><strong>Aims: </strong>This study aimed to identify the distinct change trajectories of the Chinese visceral adiposity index (CVAI) over time and to investigate their associations with risk of type 2 diabetes mellitus (T2DM).</p><p><strong>Materials and methods: </strong>This study included 52 394 participants from the prospective project, the Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR). The CVAI was calculated using measures of age, body mass index, waist circumference, triglycerides and high-density lipoprotein cholesterol. Latent mixture modelling was conducted to fit distinct trajectory patterns. The logistic regression model was applied to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of T2DM with various CVAI trajectory patterns.</p><p><strong>Results: </strong>Four distinct CVAI trajectory patterns were identified: low-increasing, moderate-increasing, moderate high-increasing and high-increasing. Compared with low-increasing CVAI, participants with moderate-increasing (OR 1.73, 95% CI 1.49-2.00), moderate high-increasing (3.48, 3.01-4.03) and high-increasing CVAI (5.50, 4.67-6.47) had a significantly increased risk of T2DM. Similar trajectory patterns were identified in both men and women. The ORs (95% CI) for moderate-increasing, moderate high-increasing and high-increasing groups were 3.28 (2.56-4.19), 7.85 (6.09-10.13) and 13.21 (9.98-17.49) in women respectively, and 1.20 (0.99-1.45), 2.18 (1.82-2.62) and 3.60 (2.93-4.43) in men respectively, when compared to the low-increasing CVAI group. Further, significant effect modifications for age, smoking and physical activity (all P_interaction <0.05) were observed in the relationship between CVAI trajectory patterns and T2DM.</p><p><strong>Conclusions: </strong>Initially high and persistently elevated CVAI is significantly associated with an increased risk of T2DM, with a particular focus on women, younger people, nonsmokers and physically inactive individuals. Continuous monitoring of CVAI levels will benefit effective identification, early intervention and management of individuals at high risk of T2DM.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":"785-794"},"PeriodicalIF":5.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674677","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 of 'weekend warrior' and other leisure time physical activity patterns with obesity and adiposity: A cross-sectional study.","authors":"Stanley Sai-Chuen Hui, Edwin Chun-Yip Chin, Jacky Ka Wai Chan, Ben Ping-Shing Chan, James Ho-Pong Wan, Sam Wing-Sum Wong","doi":"10.1111/dom.16017","DOIUrl":"10.1111/dom.16017","url":null,"abstract":"<p><strong>Aim: </strong>To investigate the effect of different physical activity patterns on obesity.</p><p><strong>Materials and methods: </strong>Data from adults aged 17-79 years were extracted from the Hong Kong Territory-Wide Physical Fitness Survey conducted in 2011-2012 and 2021-2022. Moderate to vigorous physical activity (MVPA) patterns were collected through questionnaires and categorized as inactive (no MVPA ≥10 min), insufficiently active (<150 min MVPA/week), weekend warriors (≥150 min MVPA/week from 1 to 2 days) and regularly active (≥150 min MVPA/week from ≥3 days). The association between these activity patterns with obesity risk and body fat percentage was analysed.</p><p><strong>Results: </strong>This study included 9863 obesity data (including valid waist circumference and body mass index) and 7496 body fat data. Compared with the inactive group, the weekend warriors and regularly active individuals had lower risks of general and abdominal obesity, as well as reduced body fat. Furthermore, individuals who were insufficiently active but engaged in ≥3 days of MVPA showed significantly lower body fat and obesity risk than their inactive counterparts.</p><p><strong>Conclusion: </strong>Engaging in physical activity even once or twice a week can positively impact weight control.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":"482-489"},"PeriodicalIF":5.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142708762","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":"Development and external validation of an algorithm for self-identification of risk for microvascular complications in patients with type 1 diabetes.","authors":"Wei Liu, Xiaodan Hu, Yayu Fang, Shenda Hong, Yu Zhu, Mingxia Zhang, Siqian Gong, Xiangqing Wang, Chu Lin, Rui Zhang, Sai Yin, Juan Li, Yongran Huo, Xiaoling Cai, Linong Ji","doi":"10.1111/dom.16068","DOIUrl":"10.1111/dom.16068","url":null,"abstract":"<p><strong>Aims: </strong>Microvascular complications, such as diabetic retinopathy (DR), diabetic nephropathy (DN) and diabetic peripheral neuropathy (DPN), are common and serious outcomes of inadequately managed type 1 diabetes (T1D). Timely detection and intervention in these complications are crucial for improving patient outcomes. This study aimed to develop and externally validate machine learning (ML) models for self-identification of microvascular complication risks in T1D population.</p><p><strong>Materials and methods: </strong>Utilizing data from the Chinese Type 1 Diabetes Comprehensive Care Pathway program, 911 T1D patients and 15 patient self-reported variables were included. Combined with XGBoost algorithm and cross-validation, self-identification models were constructed with 5 variables selected by feature importance ranking. For external validation, an online survey was conducted within a nationwide T1D online community (N = 157). The area under the receiver-operating-characteristic curve (AUROC) was adopted as the main metric to evaluate the model performance. The SHapley Additive exPlanation was utilized for model interpretation.</p><p><strong>Results: </strong>The prevalence rates of microvascular complications in the development set and external validation set were as follows: DR 7.0% and 12.7% (p = 0.013), DN 5.9% and 3.2% (p = 0.162) and DPN 10.5% and 20.4% (p < 0.001). The models demonstrated the AUROC values of 0.889 for DR, 0.844 for DN and 0.839 for DPN during internal validation. For external validation, the AUROC values achieved 0.762 for DR, 0.718 for DN and 0.721 for DPN.</p><p><strong>Conclusions: </strong>ML models, based on self-reported data, have the potential to serve as a self-identification tool, empowering T1D patients to understand their risks outside of hospital settings and encourage early engagement with healthcare services.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":"740-749"},"PeriodicalIF":5.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142708841","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":"Development of a predictive model for gastrointestinal side effects of metformin treatment in Chinese individuals with type 2 diabetes based on four randomised clinical trials.","authors":"Weihao Wang, Yujia Han, Xun Jiang, Jian Shao, Jia Zhang, Kaixin Zhou, Wenying Yang, Qi Pan, Zedong Nie, Lixin Guo","doi":"10.1111/dom.16095","DOIUrl":"10.1111/dom.16095","url":null,"abstract":"<p><strong>Aims: </strong>This study aimed to build a model-based predictive approach to evaluate the gastrointestinal side effects following an initial metformin medication.</p><p><strong>Materials and methods: </strong>The model was developed from data from four randomised clinical cohorts. A prediction model was established using integrated or simplified indicators. Ten machine learning models were used for the construction of predictive models. The Shapley values were used to report the features' contribution.</p><p><strong>Results: </strong>Four randomised clinical trial cohorts, including 1736 patients with type 2 diabetes, were first included in the analysis. Seventy percent of participants (1216) were allocated to the training set, 15% (260) were assigned to the internal validation set and 15% (260) were assigned to the test set. The Extra Tree model had the highest area under curve (AUC) (0.87) in the validation and test set. The top five crucial indicators were blood urea nitrogen (BUN), sex, triglyceride (TG), high-density lipoprotein-cholesterol (HDL-C) and total cholesterol (TC), and these five indicators were selected for constructing a simplified predictive model (AUC = 0.76). An online web-based tool was established based on the predictive model with integrated 17 features and top five indicators.</p><p><strong>Conclusions: </strong>To predict gastrointestinal side effects in diabetic patients for initial use of metformin, a few easily obtained features are needed to establish the model. The model can be applied to the Chinese population in clinical practice.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":"953-964"},"PeriodicalIF":5.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749468","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":"Benefits of combining SGLT2 inhibitors and pioglitazone on risk of MASH in type 2 diabetes-A real-world study.","authors":"Chi-Ho Lee, David Tak-Wai Lui, Lung-Yi Mak, Carol Ho-Yi Fong, Kylie Sze-Wing Chan, Jimmy Ho-Cheung Mak, Chloe Yu-Yan Cheung, Wing-Sun Chow, Yu-Cho Woo, Man-Fung Yuen, Wai-Kay Seto, Karen Siu-Ling Lam","doi":"10.1111/dom.16049","DOIUrl":"10.1111/dom.16049","url":null,"abstract":"<p><strong>Aims: </strong>Both pioglitazone and glucagon-like peptide 1 receptor agonists (GLP1RA) alone improve metabolic dysfunction-associated steatohepatitis (MASH) in randomized clinical trials, whereas preclinical studies suggested MASH benefits with sodium glucose co-transporter 2 inhibitors (SGLT2i). In the real world, patients with type 2 diabetes often require multiple agents for glycaemic control. Here, we investigated the benefits of combining these agents on risks of MASH.</p><p><strong>Materials and methods: </strong>Longitudinal changes in FibroScan-aspartate aminotransferase (FAST) score were measured in 888 patients with type 2 diabetes. Use of pioglitazone, GLP1RA and/or SGLT2i was defined as continuous prescriptions of ≥180 days prior to their last reassessment FibroScan. Multivariable logistic regression analysis was conducted to evaluate the associations between use of these agents and FAST score changes.</p><p><strong>Results: </strong>Over a median follow-up of 3.9 years, the increasing number of these agents used was significantly associated with more reductions in FAST score (p for trend <0.01). Dual combination was independently associated with a higher likelihood of achieving low FAST score at reassessment than single use of any of these agents (odds ratio [OR] 2.84, p = 0.01). Among the different drug combinations, using SGLT2i and pioglitazone (median dose 15 mg daily) together, as compared to not using any of these three agents, was associated with a higher likelihood of both low FAST score at reassessment (OR 6.51, p = 0.008) and FAST score regression (OR 12.52, p = 0.009), after adjusting for changes in glycaemic control and body weight during the study.</p><p><strong>Conclusions: </strong>Combining SGLT2i and pioglitazone is a potentially useful strategy to ameliorate 'at-risk' MASH in patients with type 2 diabetes.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":"574-582"},"PeriodicalIF":5.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574946","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":"Glycaemic response to pasta from three different wheat varieties in individuals with type 2 diabetes.","authors":"Ilaria Dicembrini, Giuseppe Cavallo, Francesco Ranaldi, Daniele Scoccimarro, Chiara Caiulo, Giovanni A Silverii, Paolo Iovino, Camilla E Magi, Guglielmo Bonaccorsi, Laura Rasero, Edoardo Mannucci","doi":"10.1111/dom.16082","DOIUrl":"10.1111/dom.16082","url":null,"abstract":"","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":"1014-1017"},"PeriodicalIF":5.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142714981","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":"Discontinuation of SGLT2i in people with type 2 diabetes following hospitalisation for heart failure: A cause for concern?","authors":"Tamara Y Milder, Jialing Lin, Sallie-Anne Pearson, Juliana de Oliveira Costa, Brendon L Neuen, Carol Pollock, Min Jun, Jerry R Greenfield, Richard O Day, Sophie L Stocker, David Brieger, Michael O Falster","doi":"10.1111/dom.16061","DOIUrl":"10.1111/dom.16061","url":null,"abstract":"","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":"997-1000"},"PeriodicalIF":5.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602518","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":"Increased cardiovascular risk in people with LADA in comparison to type 1 diabetes and type 2 diabetes: Findings from the DPV registry in Germany and Austria.","authors":"Rosa C Golomb, Sascha R Tittel, Alena Welters, Wolfram Karges, Svenja Meyhöfer, Michael Hummel, Julia K Mader, Jörg-C Kämmer, Nanette C Schloot, Reinhard W Holl","doi":"10.1111/dom.16048","DOIUrl":"10.1111/dom.16048","url":null,"abstract":"<p><strong>Introduction: </strong>We aimed to characterise and compare individuals diagnosed with type 1 diabetes (T1D), latent autoimmune diabetes in adults (LADA) and type 2 diabetes (T2D), in a real-world setting.</p><p><strong>Methods: </strong>Anthropometric and clinical data from 36 959 people with diabetes diagnosed at age 30-70 years enrolled in the prospective diabetes patients follow-up (DPV) registry from 1995 to 2022 were analysed cross-sectionally at diagnosis and follow-up (≥6 months after diagnosis). LADA was defined as clinical diagnosis of T2D, positivity of ≥1 islet autoantibody and an insulin-free interval of ≥6 months upon diabetes diagnosis.</p><p><strong>Results: </strong>At diagnosis, age, body mass index, waist circumference, C-peptide and HbA1c in people with LADA (n = 747) fell in between individuals with T1D (n = 940) and T2D (n = 35 272) (all p-values < 0.01). At follow-up, after adjusting for age, sex and diabetes duration, the prevalence of dyslipidemia and hypertension was the highest in people with LADA (90.6%, 77.7%) compared to people with T2D (81.8%, 60.4%) and T1D (75.7%, 39.7%) (p < 0.01). The prevalence of diabetic kidney disease (DKD) was higher in LADA (44.2%), than in T1D (19.9%) (p < 0.01). The prevalence of peripheral neuropathy was higher in individuals with LADA (55.1%) than in T2D (43.9%) and T1D (42.1%) (p < 0.05). Coverage of treatment for hypertension and dyslipidemia were 22.4% and 15.0% in T1D, 63.0% and 36.6% in LADA and 29.4% and 18.2% in T2D.</p><p><strong>Conclusion: </strong>People with LADA had a higher prevalence of cardiovascular risk factors (dyslipidemia, hypertension) and cardiovascular complications (DKD and peripheral neuropathy), suggesting that people with LADA are at need for improved recognition and care.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":"563-573"},"PeriodicalIF":5.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613078","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}