Johannes David Smeijer, Maria F Gomez, Peter Rossing, Hiddo J L Heerspink
{"title":"The effect of the endothelin receptor antagonist atrasentan on insulin resistance in phenotypic clusters of patients with type 2 diabetes and chronic kidney disease.","authors":"Johannes David Smeijer, Maria F Gomez, Peter Rossing, Hiddo J L Heerspink","doi":"10.1111/dom.16041","DOIUrl":"https://doi.org/10.1111/dom.16041","url":null,"abstract":"<p><strong>Aims: </strong>Type 2 diabetes (T2D) patients with a clinical phenotype characterized by a high degree of insulin resistance are at increased risk of chronic kidney disease (CKD). We previously demonstrated that the endothelin receptor antagonist (ERA) atrasentan reduced insulin resistance in T2D. In this study, we compared the effect of atrasentan on insulin resistance across different phenotypic clusters of patients with T2D.</p><p><strong>Materials and methods: </strong>We performed a post hoc analysis of the SONAR trial, a randomized, placebo-controlled trial of the ERA atrasentan in patients with T2D and CKD. Patients were stratified into four previously identified phenotypic clusters: severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD), mild obesity-related diabetes (MOD) and mild age-related diabetes (MARD). Changes in insulin resistance, assessed by HOMA-IR, were compared between the phenotypic clusters using a mixed effects model.</p><p><strong>Results: </strong>In total, 931 patients were included in the analysis. In the overall population, atrasentan compared to placebo reduced HOMA-IR by 12.9% [95%CI 3.5,21.4]. This effect of atrasentan was more pronounced in clusters characterized by insulin resistance or deficiency: (SIRD cluster 26.2% [95% CI 3.8,43.3] and SIDD cluster 18.5% [95%CI -3.8,35.9]), although the latter did not reach statistical significance. The effect of atrasentan compared to placebo was less pronounced in the other two clusters (MARD 12.2% [95% CI -1.7,24.12] and MOD -5.3% [95% CI -28.9,13.9]).</p><p><strong>Conclusions: </strong>Atrasentan significantly improved insulin sensitivity in patients with T2D and CKD, especially in those characterized by high insulin resistance (SIRD cluster). Further studies are warranted to investigate the long-term clinical outcomes of atrasentan treatment in these distinct phenotypic clusters.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581346","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}
Baoting He, Hugh Simon Lam, Xiu Qiu, Songying Shen, Shan Luo, Eric A W Slob, Shiu Lun Au Yeung
{"title":"Association and mediation pathways of maternal hyperglycaemia and liability to gestational diabetes with neonatal outcomes: A two-sample Mendelian randomization study.","authors":"Baoting He, Hugh Simon Lam, Xiu Qiu, Songying Shen, Shan Luo, Eric A W Slob, Shiu Lun Au Yeung","doi":"10.1111/dom.16045","DOIUrl":"https://doi.org/10.1111/dom.16045","url":null,"abstract":"<p><strong>Aims: </strong>Maternal hyperglycemia is linked to adverse neonatal outcomes. However, current evidence was insufficient for mechanistic pathways. We aim to use two-sample Mendelian randomization (MR) to obtain a comprehensive understanding of the causal association and mediation pathways.</p><p><strong>Materials and methods: </strong>Genetic variants of fasting glucose (FG), insulin sensitivity index (ISI), glycated haemoglobin (HbA1c), gestational diabetes mellitus (GDM) and type 2 diabetes (T2D) were used as instruments (N = 50 404-898 130). The associations with offspring birthweight, gestational duration, spontaneous preterm and post-term birth were assessed by the inverse-variance weighted method, using summary statistics of European genome-wide association studies (N = 131 279-210 248). Sensitivity analyses, including multivariable MR removing pleiotropic effect from maternal body mass index (BMI), assessed the robustness. Mediation via placental weight and maternal hypertension were assessed via a two-step MR design.</p><p><strong>Results: </strong>FG (0.46 SD per mmol/L, 95% confidence interval [95% CI]: 0.32, 0.61) and GDM liability (0.18 SD per log odds, 95% CI: 0.08, 0.18) were positively associated with birthweight, with consistent findings for HbA1c, T2D liability and ISI. These associations were mediated by placental weight (proportion mediated: 32.8% to 77.7%). Higher HbA1c, GDM and T2D liability were associated with preterm birth (odds ratios for GDM: 1.07, 95% CI: 1.01, 1.14) and shorter gestational duration, whilst the association for T2D attenuated after adjusted for maternal BMI and gestational hypertension.</p><p><strong>Conclusion: </strong>Maternal hyperglycemia is associated with higher birthweight (possibly indicating macrosomia), mediated via increased placental growth. GDM and T2D liability are related to preterm birth, whilst the association for T2D liability is driven by maternal adiposity.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581298","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}
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
{"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":"https://doi.org/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":""},"PeriodicalIF":5.4,"publicationDate":"2024-11-05","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}
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
{"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":"https://doi.org/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 (IC<sub>50</sub> = 2.4 nM) augmented cAMP signalling without β-arrestin-2 recruitment or receptor internalization. ECC5004 potentiated GSIS in both EndoC-βH5 cells (EC<sub>50</sub> = 5.9 nM) and in vivo in NHPs (EC<sub>50</sub> = 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":""},"PeriodicalIF":5.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Ultra-processed foods cause weight gain and increased energy intake associated with reduced chewing frequency: A randomized, open-label, crossover study.","authors":"Jimmy Chun Yu Louie","doi":"10.1111/dom.16044","DOIUrl":"https://doi.org/10.1111/dom.16044","url":null,"abstract":"","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566882","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}
Qiang He, Rujie Zheng, Wenjuan Song, Xiaotong Sun, Chengzhi Lu
{"title":"The impact of metabolic heterogeneity of obesity and transitions on cardiovascular disease incidence in Chinese middle-aged and elderly population: A nationwide prospective cohort study.","authors":"Qiang He, Rujie Zheng, Wenjuan Song, Xiaotong Sun, Chengzhi Lu","doi":"10.1111/dom.16040","DOIUrl":"https://doi.org/10.1111/dom.16040","url":null,"abstract":"<p><strong>Background: </strong>Previous studies indicated that metabolic heterogeneity of obesity would affect the risk of cardiovascular disease (CVD). However, the alterations in CVD risk associated with transitions between various metabolic health statuses influenced by obesity status remain unclear.</p><p><strong>Methods: </strong>We utilized data from the China Health and Retirement Longitudinal Study (CHARLS), a longitudinal cohort study involving Chinese residents aged 45 years and older. Baseline data were collected in 2011-2012, with follow-up surveys conducted up to 2020. Participants in the study were categorized into four body mass index-metabolic phenotypes: metabolically healthy normal weight (MHNW), metabolically healthy overweight/obesity (MHOO), metabolically unhealthy normal weight (MUNW) and metabolically unhealthy overweight/obesity (MUOO). Transitions in these phenotypes over 4 years were analysed. Cox regression models were used to assess the associations of these phenotypes and their transitions with CVD incidence.</p><p><strong>Results: </strong>Among 7721 participants, 1353 (17.5%) developed CVD during the follow-up period. Both overweight/obese and metabolically unhealthy statuses were associated with increased CVD risk. The highest risk was observed in the MUOO group (hazard ratio [HR]: 1.74, 95% confidence interval [CI]: 1.50-2.09, p < 0.0001), followed by the MUNW (HR 1.35, 95% CI: 1.13-1.66, p < 0.001) and MHOO (HR: 1.29, 95% CI: 1.08-1.56, p = 0.002) groups compared to the MHNW group. The deteriorations of obesity and metabolic health status elevated the incidence of CVD, whereas improvements in these statuses reduced the risk of CVD. Additionally, alterations in metabolic health status conferred greater benefits in overweight/obese individuals compared to those with normal weight.</p><p><strong>Conclusion: </strong>The study highlights the importance of maintaining and promoting metabolic health, particularly in overweight/obese individuals, to reduce CVD risk. Metabolic health status plays a more crucial role than obesity status in predicting CVD incidence.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574948","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}
Kimberly A Gudzune, Adam Stefanski, Dachuang Cao, Donna Mojdami, Fangyu Wang, Nadia Ahmad, Jiat Ling Poon
{"title":"Association between weight reduction achieved with tirzepatide and quality of life in adults with obesity: Results from the SURMOUNT-1 study.","authors":"Kimberly A Gudzune, Adam Stefanski, Dachuang Cao, Donna Mojdami, Fangyu Wang, Nadia Ahmad, Jiat Ling Poon","doi":"10.1111/dom.16046","DOIUrl":"https://doi.org/10.1111/dom.16046","url":null,"abstract":"<p><strong>Aims: </strong>The SURMOUNT-1 trial investigated effects of tirzepatide, a glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, on body weight in participants with obesity or overweight. This analysis evaluated changes in patient-reported outcomes (PROs) assessing physical function, psychosocial well-being, and overall health aspects of participants' health-related quality of life (HRQoL) in SURMOUNT-1.</p><p><strong>Methods: </strong>PRO instruments included the Impact of Weight on Quality of Life-Lite Clinical Trials version (IWQOL-Lite-CT), Short Form Survey-36 version 2 (SF-36v2) and EQ-5D-5L. Scores were analysed by treatment group and by categorical degree of weight reduction group: >0 to <5%, ≥5 to <10%, ≥10 to <20% and ≥20%. Relevant PROs were evaluated for participants with or without physical or psychosocial limitations at baseline, as measured by Patient Global Impression of Status for physical activity (PGIS) and Patient Health Questionnaire-2 (PHQ-2), respectively.</p><p><strong>Results: </strong>All tirzepatide groups demonstrated significant improvements in PRO scores versus placebo. There was a consistent trend of incremental PRO improvement with greater degrees of weight reduction, starting from ≥5% weight reduction. Participants achieving ≥20% weight reduction demonstrated the greatest changes from baseline to week 72 (SF-36v2 Physical Component Summary, 4.60; SF-36v2 Mental Component Summary, 0.80; IWQOL-Lite CT Total score, 24.7). Those with baseline physical and psychosocial limitations experienced greater improvements than those without.</p><p><strong>Conclusions: </strong>Tirzepatide treatment was associated with improved HRQoL compared to placebo in people with overweight or obesity. Higher percentages of weight reduction were associated with greater improvements. Clinical trial registration number for SURMOUNT-1: NCT04184622.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574945","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}
Nan Dai B.Pharm, Xiaorong Su M.Pharm, Yong Wang MD
{"title":"Cost-utility analysis of once-weekly insulin icodec and once-daily insulin glargine in patients with type 2 diabetes receiving basal-bolus insulin therapy in China","authors":"Nan Dai B.Pharm, Xiaorong Su M.Pharm, Yong Wang MD","doi":"10.1111/dom.16031","DOIUrl":"10.1111/dom.16031","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The purpose of this study is to explore the rational pricing range for the once-weekly administration of insulin icodec in the treatment of type 2 diabetes patients in China who have already received basal insulin therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The data foundation of this study originates from the ONWARDS 4 clinical trial and research materials on Chinese type 2 diabetes patients. By comprehensively applying cost-utility analysis methods and binary search techniques, the appropriate price positioning of insulin icodec was determined from the perspective of China's healthcare system.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the long-term treatment simulation, we found that insulin icodec and insulin glargine performed similarly in terms of quality-adjusted life years (QALYs), with 10.15 and 10.07 years, respectively. Although the annual cost of insulin icodec was initially assumed to be equivalent to that of insulin glargine, in-depth analysis revealed that insulin icodec may have higher cost-effectiveness potential. Further price sensitivity analysis indicated that the reasonable cost range of insulin icodec lies between $851.95 and $1358.25. After fine-tuning through univariate sensitivity analysis, this cost range was revised to $784.90 to $1145.96, a conclusion that was robustly validated in subsequent probabilistic sensitivity analysis and scenario simulations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The conclusion drawn from this study is that, with insulin glargine as the cost reference, the economic cost of insulin icodec for Chinese type 2 diabetes patients is expected to range from $784.90 to $1145.96, providing a reference basis for clinical decision-making and healthcare policy formulation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":"27 1","pages":"377-386"},"PeriodicalIF":5.4,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542346","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}
Jing Ma MD, Yuyan Dong MM, Juxiang Liu MD, Shuo Gao MD, Jinxing Quan MD
{"title":"The role of GRB2 in diabetes, diabetes complications and related disorders","authors":"Jing Ma MD, Yuyan Dong MM, Juxiang Liu MD, Shuo Gao MD, Jinxing Quan MD","doi":"10.1111/dom.16015","DOIUrl":"10.1111/dom.16015","url":null,"abstract":"<p>Growth factor receptor-bound protein 2 (GRB2) is a key adaptor protein involved in multiple signalling pathways, and its dysregulation is associated with various diseases. Type 2 diabetes is a systemic condition characterized by insulin resistance and impaired β-cell function. The complications of diabetes significantly reduce life expectancy and quality of life, imposing a substantial burden on society. However, the role of GRB2 in diabetes and associated complications is largely unknown. Emerging evidence suggests that GRB2 plays a crucial role in insulin resistance, inflammation, immune activation and the regulation of cellular processes such as cell proliferation, growth, metabolism, angiogenesis, apoptosis and differentiation. Dysregulation of GRB2-mediated pathways contributes to the progression of diabetic neuropathy, cognitive dysfunction, nephropathy, retinopathy and related disorders. This review provides a comprehensive overview of the current understanding of the role of GRB2 in diabetes, diabetes complications and related disorders, alongside recent advances in the development of GRB2-targeted therapies. Elucidating the complex role of GRB2 in these disorders provides valuable insights into potential therapeutic strategies targeting GRB2-mediated pathways.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":"27 1","pages":"23-34"},"PeriodicalIF":5.4,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542347","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}