Type 1 diabetes (T1D) and celiac disease (CeD) are two strongly associated autoimmune disorders, as they share genetic risk factors and immunopathogenic mechanisms. Several studies suggest an implication of gluten proteins, the causative antigen of CeD, in T1D pathogenesis. We investigated whether a gliadin-specific T-cell reactivity is present in the gut mucosa of children with T1D, with or without CeD comorbidity. Thirty-three young children were enrolled (median age 10 years) and divided in five groups based on T1D and/or CeD diagnosis. All patients underwent upper endoscopy for suspicion of CeD or gastrointestinal complaints, and duodenal biopsy specimens were processed for analysis of lymphoid cells phenotype and T cell–mediated reactiveness to gliadin. No substantial differences were found in the percentages of various T-cell subsets between the groups. No gliadin T-cell reactivity was found in T1D children negative for CeD, also in the presence of antibodies neutralizing regulatory cytokines interleukin 10 and transforming growth factor β. By contrast, a marked T-cell response to gliadin was detected in T1D with either potential (positive for CeD-associated autoantibodies and normal mucosa histology) or full-blown CeD (villous atrophy). In conclusion, no adaptive immunity to gluten occurs in the small intestine of T1D children in the absence of CeD comorbidity. Article Highlights It has been hypothesized that dietary proteins act as environmental factors in type 1 diabetes pathogenesis. This study investigated whether gliadin-specific T cells are present in the small intestine of children with type 1 diabetes, without or with celiac disease comorbidity. No sign of gliadin-reactive T cells, either proinflammatory or regulatory, was observed in the gut mucosa of children with type 1 diabetes negative for celiac disease autoimmunity. Interferon-γ producing T cells were detected in gut mucosa biopsy specimens of children with diabetes seropositive for antitissue transglutaminase antibodies. Our study does not support a pathogenic role of intestinal T cell–mediated immunity to gluten in type 1 diabetes pathogenesis.
{"title":"T-Cell Mediated Immunity to Gliadin Is Elicited in the Gut Mucosa of Type 1 Diabetes Patients Only in Presence of Celiac Disease Comorbidity","authors":"Carmen Gianfrani, Alessandra Camarca, Stefania Picascia, Serena Vitale, Ilaria Mottola, Martina Carpinelli, Mariantonia Maglio, Silvia Gregori, Adriana Franzese, Renata Auricchio, Riccardo Troncone","doi":"10.2337/db24-1120","DOIUrl":"https://doi.org/10.2337/db24-1120","url":null,"abstract":"Type 1 diabetes (T1D) and celiac disease (CeD) are two strongly associated autoimmune disorders, as they share genetic risk factors and immunopathogenic mechanisms. Several studies suggest an implication of gluten proteins, the causative antigen of CeD, in T1D pathogenesis. We investigated whether a gliadin-specific T-cell reactivity is present in the gut mucosa of children with T1D, with or without CeD comorbidity. Thirty-three young children were enrolled (median age 10 years) and divided in five groups based on T1D and/or CeD diagnosis. All patients underwent upper endoscopy for suspicion of CeD or gastrointestinal complaints, and duodenal biopsy specimens were processed for analysis of lymphoid cells phenotype and T cell–mediated reactiveness to gliadin. No substantial differences were found in the percentages of various T-cell subsets between the groups. No gliadin T-cell reactivity was found in T1D children negative for CeD, also in the presence of antibodies neutralizing regulatory cytokines interleukin 10 and transforming growth factor β. By contrast, a marked T-cell response to gliadin was detected in T1D with either potential (positive for CeD-associated autoantibodies and normal mucosa histology) or full-blown CeD (villous atrophy). In conclusion, no adaptive immunity to gluten occurs in the small intestine of T1D children in the absence of CeD comorbidity. Article Highlights It has been hypothesized that dietary proteins act as environmental factors in type 1 diabetes pathogenesis. This study investigated whether gliadin-specific T cells are present in the small intestine of children with type 1 diabetes, without or with celiac disease comorbidity. No sign of gliadin-reactive T cells, either proinflammatory or regulatory, was observed in the gut mucosa of children with type 1 diabetes negative for celiac disease autoimmunity. Interferon-γ producing T cells were detected in gut mucosa biopsy specimens of children with diabetes seropositive for antitissue transglutaminase antibodies. Our study does not support a pathogenic role of intestinal T cell–mediated immunity to gluten in type 1 diabetes pathogenesis.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"1 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144479186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
SILVIO E. INZUCCHI, ROHANA ABDUL GHANI, JOHN DEANFIELD, MADS D.M. ENGELMANN, G. KEES HOVINGH, OLE K. JEPPESEN, MONIKA KELLERER, KABIRDEV MANDAVYA, JOHANNES F. MANN, NIKOLAUS MARX, CHANTAL MATHIEU, DARREN K. MCGUIRE, VISWANATHAN MOHAN, SHARON L. MULVAGH, RODICA POP-BUSUI, NEIL R. POULTER, MARIA SEJERSTEN RIPA, GABRIELA ROMAN, RÓBINSON SÁNCHEZ GARCÍA, MICHAEL SHECHTER, JOHN B. BUSE
Introduction and Objective: In SOUL (NCT03914326), oral semaglutide (sema) 14 mg QD, a GLP-1 receptor agonist, reduced major adverse cardiovascular (CV) event (MACE) risk by 14%. GLP-1RAs are routinely prescribed to reduce A1c and BMI in type 2 diabetes (T2D). Whether the CV benefits of oral sema are influenced by baseline A1c or BMI is not fully known. Methods: SOUL’s primary outcome was time to first MACE, assessed for this post hoc analysis by baseline A1c, BMI and body weight using Cox regression. Results: People with T2D (n=9650; A1c 6.5–10%) and known atherosclerotic CV disease (ASCVD) or chronic kidney disease (CKD) were randomized to oral sema or placebo and followed for a mean of 47.5 months. We found significant differences in MACE outcomes associated with oral sema use by baseline A1c, with greater effects apparent with A1c >8.0% (Fig.). When the data were further analyzed across four A1c strata, the MACE benefit from oral sema appeared to apply to those with A1c >7%. The effects of oral sema on MACE were the same in those with BMI above / below 30 kg/m2, as well as across all four BMI strata, and above / below the mean body weight (87.9 kg) (Fig.). Conclusion: In SOUL, the CV benefits of oral sema appeared more pronounced with higher A1c levels at baseline but were consistent across various BMI categories. These data may help inform the individualized use of oral sema in people with T2D and ASCVD and/or CKD. Disclosure S.E. Inzucchi: Consultant; Novo Nordisk, AstraZeneca, Boehringer-Ingelheim, Merck & Co., Inc, Pfizer Inc, Bayer Pharmaceuticals, Inc. R. Abdul Ghani: None. J. Deanfield: Other Relationship; Aegerion Pharmaceuticals, Amgen Inc, AstraZeneca, Bayer Pharmaceuticals, Inc, Boehringer-Ingelheim, Merck & Co., Inc, Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Novo Nordisk A/S, Pfizer Inc. M.D.M. Engelmann: Employee; Novo Nordisk. G. Hovingh: Employee; Novo Nordisk. Stock/Shareholder; Novo Nordisk. O.K. Jeppesen: None. M. Kellerer: Advisory Panel; Abbott, Bayer Pharmaceuticals, Inc. Speaker's Bureau; Boehringer-Ingelheim, Johnson & Johnson Medical Devices Companies. Advisory Panel; Lilly Diabetes. Speaker's Bureau; Lilly Diabetes. Advisory Panel; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Advisory Panel; Sanofi. K. Mandavya: Employee; Novo Nordisk. J.F. Mann: Other Relationship; AstraZeneca, Bayer Pharmaceuticals, Inc. Advisory Panel; Novo Nordisk. Board Member; AstraZeneca, Bayer Pharmaceuticals, Inc, Boehringer-Ingelheim, Novo Nordisk. Other Relationship; Sanofi. Consultant; AstraZeneca, Bayer Pharmaceuticals, Inc, Novo Nordisk. Research Support; AstraZeneca. Other Relationship; Boehringer-Ingelheim. Research Support; Novo Nordisk, Sanofi. Speaker's Bureau; AstraZeneca, Bayer Pharmaceuticals, Inc, Novo Nordisk, Novartis AG. Other Relationship; UpToDate Inc / KDIGO. N. Marx: Speaker's Bureau; Abbott, Amgen Inc, AstraZeneca. Advisory Panel; AstraZeneca. Speaker's Bureau; Bayer Pharmaceutica
{"title":"292-OR: Oral Semaglutide and Cardiovascular Outcomes by Baseline A1C and BMI in People with Type 2 Diabetes in the SOUL Trial","authors":"SILVIO E. INZUCCHI, ROHANA ABDUL GHANI, JOHN DEANFIELD, MADS D.M. ENGELMANN, G. KEES HOVINGH, OLE K. JEPPESEN, MONIKA KELLERER, KABIRDEV MANDAVYA, JOHANNES F. MANN, NIKOLAUS MARX, CHANTAL MATHIEU, DARREN K. MCGUIRE, VISWANATHAN MOHAN, SHARON L. MULVAGH, RODICA POP-BUSUI, NEIL R. POULTER, MARIA SEJERSTEN RIPA, GABRIELA ROMAN, RÓBINSON SÁNCHEZ GARCÍA, MICHAEL SHECHTER, JOHN B. BUSE","doi":"10.2337/db25-292-or","DOIUrl":"https://doi.org/10.2337/db25-292-or","url":null,"abstract":"Introduction and Objective: In SOUL (NCT03914326), oral semaglutide (sema) 14 mg QD, a GLP-1 receptor agonist, reduced major adverse cardiovascular (CV) event (MACE) risk by 14%. GLP-1RAs are routinely prescribed to reduce A1c and BMI in type 2 diabetes (T2D). Whether the CV benefits of oral sema are influenced by baseline A1c or BMI is not fully known. Methods: SOUL’s primary outcome was time to first MACE, assessed for this post hoc analysis by baseline A1c, BMI and body weight using Cox regression. Results: People with T2D (n=9650; A1c 6.5–10%) and known atherosclerotic CV disease (ASCVD) or chronic kidney disease (CKD) were randomized to oral sema or placebo and followed for a mean of 47.5 months. We found significant differences in MACE outcomes associated with oral sema use by baseline A1c, with greater effects apparent with A1c >8.0% (Fig.). When the data were further analyzed across four A1c strata, the MACE benefit from oral sema appeared to apply to those with A1c >7%. The effects of oral sema on MACE were the same in those with BMI above / below 30 kg/m2, as well as across all four BMI strata, and above / below the mean body weight (87.9 kg) (Fig.). Conclusion: In SOUL, the CV benefits of oral sema appeared more pronounced with higher A1c levels at baseline but were consistent across various BMI categories. These data may help inform the individualized use of oral sema in people with T2D and ASCVD and/or CKD. Disclosure S.E. Inzucchi: Consultant; Novo Nordisk, AstraZeneca, Boehringer-Ingelheim, Merck & Co., Inc, Pfizer Inc, Bayer Pharmaceuticals, Inc. R. Abdul Ghani: None. J. Deanfield: Other Relationship; Aegerion Pharmaceuticals, Amgen Inc, AstraZeneca, Bayer Pharmaceuticals, Inc, Boehringer-Ingelheim, Merck & Co., Inc, Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Novo Nordisk A/S, Pfizer Inc. M.D.M. Engelmann: Employee; Novo Nordisk. G. Hovingh: Employee; Novo Nordisk. Stock/Shareholder; Novo Nordisk. O.K. Jeppesen: None. M. Kellerer: Advisory Panel; Abbott, Bayer Pharmaceuticals, Inc. Speaker's Bureau; Boehringer-Ingelheim, Johnson & Johnson Medical Devices Companies. Advisory Panel; Lilly Diabetes. Speaker's Bureau; Lilly Diabetes. Advisory Panel; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Advisory Panel; Sanofi. K. Mandavya: Employee; Novo Nordisk. J.F. Mann: Other Relationship; AstraZeneca, Bayer Pharmaceuticals, Inc. Advisory Panel; Novo Nordisk. Board Member; AstraZeneca, Bayer Pharmaceuticals, Inc, Boehringer-Ingelheim, Novo Nordisk. Other Relationship; Sanofi. Consultant; AstraZeneca, Bayer Pharmaceuticals, Inc, Novo Nordisk. Research Support; AstraZeneca. Other Relationship; Boehringer-Ingelheim. Research Support; Novo Nordisk, Sanofi. Speaker's Bureau; AstraZeneca, Bayer Pharmaceuticals, Inc, Novo Nordisk, Novartis AG. Other Relationship; UpToDate Inc / KDIGO. N. Marx: Speaker's Bureau; Abbott, Amgen Inc, AstraZeneca. Advisory Panel; AstraZeneca. Speaker's Bureau; Bayer Pharmaceutica","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"188 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144370523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yingchai Zhang, Eric S.H. Lau, Claudia H.T. Tam, Noel Y.H. Ng, Mai Shi, Atta Y.T. Tsang, Hanbin Wu, Aimin Yang, Hongjiang Wu, Lai Yuk Yuen, Elaine Y.K. Chow, Andrea O.Y. Luk, Alice P.S. Kong, Chi Chiu Wang, Juliana C.N. Chan, Wing Hung Tam, Ronald C.W. Ma
Early-life exposures may shape long-term effects on glucose regulation. This study aimed to stratify long-term abnormal glucose tolerance (AGT) risk from early childhood. A total of 906 children were enrolled at baseline and reevaluated in adolescence and young adulthood. By using the latent class trajectory analysis, glucose trajectories of children were measured via five–time point oral glucose tolerance tests and then grouped into three latent subclasses: mild excursion–normal reversion (MN), moderate excursion–delayed reversion (MD), and severe excursion–delayed reversion (SD). Logistic regression was performed to estimate the risk of AGT and associations between cardiometabolic factors and subclasses. In adolescence, compared with the MN subclass, the risk of AGT was 1.7-fold in the MD subclass and 5.5-fold in the SD subclass, after adjusting for age, sex, BMI, and Tanner stage. In young adulthood, the adjusted risk of AGT was 3.6-fold and 11.6-fold in the MD and SD subclasses, respectively. During the full natural history of glucose tolerance, the risk of AGT was 3.6-fold in the MD subclass and 18.1-fold in the SD subclass, after adjusting for childhood covariates. MD and SD subclass membership was strongly associated with childhood hypertension, maternal gestational diabetes, and maternal hypertension during pregnancy. Glucose trajectory subclasses in early childhood effectively stratified the long-term risk of AGT. The association between maternal cardiometabolic health and childhood subclass membership highlighted that prenatal exposures may influence metabolic outcomes in offspring. Article Highlights Abnormal glucose tolerance (AGT) in youth has become an alarming global public health issue; however, approaches to identify high-risk population among young people have not been well-established. Can the long-term risk of AGT be stratified by the subclasses of glucose trajectories defined in childhood? Subclasses defined in childhood can efficiently stratify the risk of AGT in adolescence and young adulthood. The subclass membership was strongly associated with cardiometabolic disorders in childhood and maternal cardiometabolic disorders during pregnancy. This subclass method provides a potential strategy to identify those at risk of later cardiometabolic disorders from childhood for more intensive evaluation of intervention. The close relationship between maternal cardiometabolic disorders and subclass membership of children highlighted the potential influence of gestational cardiometabolic health on the development of cardiometabolic disorders in offspring.
{"title":"Subclasses of Glucose Trajectories in Early Childhood Stratified the Risk of Abnormal Glucose Tolerance in Adolescence and Young Adulthood","authors":"Yingchai Zhang, Eric S.H. Lau, Claudia H.T. Tam, Noel Y.H. Ng, Mai Shi, Atta Y.T. Tsang, Hanbin Wu, Aimin Yang, Hongjiang Wu, Lai Yuk Yuen, Elaine Y.K. Chow, Andrea O.Y. Luk, Alice P.S. Kong, Chi Chiu Wang, Juliana C.N. Chan, Wing Hung Tam, Ronald C.W. Ma","doi":"10.2337/db25-0256","DOIUrl":"https://doi.org/10.2337/db25-0256","url":null,"abstract":"Early-life exposures may shape long-term effects on glucose regulation. This study aimed to stratify long-term abnormal glucose tolerance (AGT) risk from early childhood. A total of 906 children were enrolled at baseline and reevaluated in adolescence and young adulthood. By using the latent class trajectory analysis, glucose trajectories of children were measured via five–time point oral glucose tolerance tests and then grouped into three latent subclasses: mild excursion–normal reversion (MN), moderate excursion–delayed reversion (MD), and severe excursion–delayed reversion (SD). Logistic regression was performed to estimate the risk of AGT and associations between cardiometabolic factors and subclasses. In adolescence, compared with the MN subclass, the risk of AGT was 1.7-fold in the MD subclass and 5.5-fold in the SD subclass, after adjusting for age, sex, BMI, and Tanner stage. In young adulthood, the adjusted risk of AGT was 3.6-fold and 11.6-fold in the MD and SD subclasses, respectively. During the full natural history of glucose tolerance, the risk of AGT was 3.6-fold in the MD subclass and 18.1-fold in the SD subclass, after adjusting for childhood covariates. MD and SD subclass membership was strongly associated with childhood hypertension, maternal gestational diabetes, and maternal hypertension during pregnancy. Glucose trajectory subclasses in early childhood effectively stratified the long-term risk of AGT. The association between maternal cardiometabolic health and childhood subclass membership highlighted that prenatal exposures may influence metabolic outcomes in offspring. Article Highlights Abnormal glucose tolerance (AGT) in youth has become an alarming global public health issue; however, approaches to identify high-risk population among young people have not been well-established. Can the long-term risk of AGT be stratified by the subclasses of glucose trajectories defined in childhood? Subclasses defined in childhood can efficiently stratify the risk of AGT in adolescence and young adulthood. The subclass membership was strongly associated with cardiometabolic disorders in childhood and maternal cardiometabolic disorders during pregnancy. This subclass method provides a potential strategy to identify those at risk of later cardiometabolic disorders from childhood for more intensive evaluation of intervention. The close relationship between maternal cardiometabolic disorders and subclass membership of children highlighted the potential influence of gestational cardiometabolic health on the development of cardiometabolic disorders in offspring.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"9 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144370522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A growing number of micropeptides (miPs) have been identified in recent years, but their biological roles remain largely unexplored. We identified a conserved 6-kDa miP, named small integral membrane protein 30 (SMIM30), as a potential metabolic regulator. To study the physiological function of Smim30, we generated a loss-of-function mouse strain using the CRISPR/Cas9-mediated knock-in strategy. When fed both normal chow and high-fat diets, these mice exhibited elevated blood glucose and insulin levels, with reduced insulin sensitivity. We further showed that Smim30 loss in adipose tissue drove systemic insulin resistance, although intriguingly, adipocyte-expressed Smim30 was dispensable in this effect. Instead, Smim30 was mainly expressed in adipose tissue–residential macrophages, and loss of Smim30 led to increased macrophage infiltration and production of proinflammatory cytokines and chemokines. Smim30 also modulated inflammatory responses in ex vivo/in vitro macrophage systems, which are conserved in both humans and mice. The results indicate that Smim30 plays a key role in maintaining adipose tissue insulin sensitivity and safeguarding systemic metabolic homeostasis, offering potential as both a diagnostic biomarker and therapeutic target for metabolic disorders. Article Highlights Understanding the role of micropeptides (miPs) in metabolic regulation could enhance insights into metabolic diseases and open new pathways for treatment. Small integral membrane protein 30 (Smim30), an adipose tissue macrophage–expressed miP, maintains insulin sensitivity and safeguards systemic metabolic homeostasis. Smim30 modulates inflammatory responses and macrophage–adipocyte communication in adipose tissue. Smim30 could serve as a potential diagnostic biomarker and therapeutic target for metabolic disorders.
{"title":"Macrophage-Expressed Micropeptide Smim30 Maintains Adipose Tissue Insulin Sensitivity and Safeguards Systemic Metabolic Homeostasis","authors":"Yonghe Ma, Yu Shi, Kaiyuan Wu, Ping Li, Nikhil Gupta, Chengfei Jiang, Hang Sun, Xiangbo Ruan, Tyler Finley, Jing Wu, Chengyu Liu, Haiming Cao","doi":"10.2337/db24-0721","DOIUrl":"https://doi.org/10.2337/db24-0721","url":null,"abstract":"A growing number of micropeptides (miPs) have been identified in recent years, but their biological roles remain largely unexplored. We identified a conserved 6-kDa miP, named small integral membrane protein 30 (SMIM30), as a potential metabolic regulator. To study the physiological function of Smim30, we generated a loss-of-function mouse strain using the CRISPR/Cas9-mediated knock-in strategy. When fed both normal chow and high-fat diets, these mice exhibited elevated blood glucose and insulin levels, with reduced insulin sensitivity. We further showed that Smim30 loss in adipose tissue drove systemic insulin resistance, although intriguingly, adipocyte-expressed Smim30 was dispensable in this effect. Instead, Smim30 was mainly expressed in adipose tissue–residential macrophages, and loss of Smim30 led to increased macrophage infiltration and production of proinflammatory cytokines and chemokines. Smim30 also modulated inflammatory responses in ex vivo/in vitro macrophage systems, which are conserved in both humans and mice. The results indicate that Smim30 plays a key role in maintaining adipose tissue insulin sensitivity and safeguarding systemic metabolic homeostasis, offering potential as both a diagnostic biomarker and therapeutic target for metabolic disorders. Article Highlights Understanding the role of micropeptides (miPs) in metabolic regulation could enhance insights into metabolic diseases and open new pathways for treatment. Small integral membrane protein 30 (Smim30), an adipose tissue macrophage–expressed miP, maintains insulin sensitivity and safeguards systemic metabolic homeostasis. Smim30 modulates inflammatory responses and macrophage–adipocyte communication in adipose tissue. Smim30 could serve as a potential diagnostic biomarker and therapeutic target for metabolic disorders.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"57 74 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144370524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
LUCAS S. MATZENBACHER, FREDERICO L. DA COSTA, LAURA G.B. DE BARROS, VICENZO GHENO, ISABELA S. MAIA, LUIZA M. BLANK, MARIA ANTÔNIA B. BRUM, LUCAS F. FONTOURA, JANINE ALESSI, GABRIELA H. TELO
Introduction and Objective: This study evaluated the impact of an interactive virtual assistant device, programmed with a behavioral intervention model, on mental-health and diabetes-related outcomes in older adults with type 2 diabetes (T2D) Methods: We conducted a randomized controlled trial enrolling participants aged 65 years or older with T2D. Participants were randomized to receive a Smart Speaker EchoDot 3rd Gen device, programmed with a behavioral intervention that included automatic medication reminders and health tips, or to continue with usual care for 12 weeks. The primary outcome was mental distress, assessed using the SRQ-20 scale. Secondary outcomes included quality of life (measured with the SF-36 scale), adherence to diabetes self-care behaviors (assessed with the SCI-R scale), and HbA1c. An analysis of covariance model was used to evaluate the impact of the intervention on study outcomes. Between-group mean differences after the intervention period, adjusted for baseline data and relevant covariates, were reported, with statistical significance set at an alpha level of 0.05 Results: A total of 112 participants (63% female, 63% white; mean age: 72.5 years; mean T2D duration: 16.9 years; mean HbA1c: 7.9%) were randomized, with 103 completing the trial. At 12 weeks, participants in the intervention group showed a reduction in mental distress (mean difference: -1.46; 95% CI -2.73 to -0.19; p=0.024), an increase in quality of life (mean difference: 9.46; 95% CI 3.65 to 15.26; p=0.001), greater adherence to diabetes self-care behaviors (mean difference: 3.40; 95% CI 1.61 to 5.19; p<0.001), and lower HbA1c (mean difference: -0.48; 95% CI -0.85 to -0.11; p=0.011) when compared to those in the usual care group Conclusion: In this randomized controlled trial, a smart-speaker-based intervention was associated with significant improvements in mental health, quality of life, diabetes self-care behaviors, and HbA1c in older adults with T2D Disclosure L.S. Matzenbacher: None. F.L. da Costa: None. L.G.B. de Barros: None. V. Gheno: None. I.S. Maia: None. L.M. Blank: None. M.B. Brum: None. L.F. Fontoura: None. J. Alessi: None. G.H. Telo: None. Funding Brazilian National Council for Scientific and Technological Development (CNPq/MCTI/FNDCT 18/2021 grant)
简介和目的：本研究评估了一种带有行为干预模型的交互式虚拟辅助设备对老年2型糖尿病（T2D）患者心理健康和糖尿病相关结局的影响。方法：我们进行了一项随机对照试验，招募了65岁及以上的T2D患者。参与者随机接受智能扬声器EchoDot第三代设备，该设备带有行为干预程序，包括自动药物提醒和健康提示，或者继续接受12周的常规护理。主要结果为精神痛苦，采用SRQ-20量表进行评估。次要结果包括生活质量（用SF-36量表测量）、糖尿病自我护理行为的依从性（用SCI-R量表评估）和HbA1c。采用协方差分析模型评价干预对研究结果的影响。经基线资料及相关协变量调整后，报告干预期后组间平均差异，alpha水平为0.05，差异有统计学意义。结果：共有112名参与者(63%女性，63%白人；平均年龄：72.5岁；T2D平均病程：16.9年；平均HbA1c: 7.9%)被随机分组，103人完成了试验。在12周时，干预组的参与者表现出精神痛苦的减少(平均差异：-1.46；95% CI -2.73 ~ -0.19；P =0.024)，生活质量提高(平均差值：9.46；95% CI 3.65 ~ 15.26；P =0.001)，更坚持糖尿病自我护理行为(平均差异：3.40；95% CI 1.61 ~ 5.19；p<0.001)和较低的HbA1c(平均差异：-0.48；95% CI -0.85 ~ -0.11；p=0.011)结论：在这项随机对照试验中，基于智能扬声器的干预与老年T2D患者的心理健康、生活质量、糖尿病自我护理行为和HbA1c的显著改善相关。达·科斯塔：没有。L.G.B. de Barros：没有。V. Gheno：没有。I.S.玛雅：没有。L.M.布兰克：没有。M.B.布鲁姆：没有。l·f·丰图拉：没有。J.阿莱西：没有。G.H.泰罗：没有。资助巴西国家科学和技术发展委员会（CNPq/MCTI/FNDCT 18/2021赠款）
{"title":"297-OR: Interactive Virtual Assistant for Health Promotion and Diabetes Care in Older Adults with Diabetes—A Randomized Controlled Trial","authors":"LUCAS S. MATZENBACHER, FREDERICO L. DA COSTA, LAURA G.B. DE BARROS, VICENZO GHENO, ISABELA S. MAIA, LUIZA M. BLANK, MARIA ANTÔNIA B. BRUM, LUCAS F. FONTOURA, JANINE ALESSI, GABRIELA H. TELO","doi":"10.2337/db25-297-or","DOIUrl":"https://doi.org/10.2337/db25-297-or","url":null,"abstract":"Introduction and Objective: This study evaluated the impact of an interactive virtual assistant device, programmed with a behavioral intervention model, on mental-health and diabetes-related outcomes in older adults with type 2 diabetes (T2D) Methods: We conducted a randomized controlled trial enrolling participants aged 65 years or older with T2D. Participants were randomized to receive a Smart Speaker EchoDot 3rd Gen device, programmed with a behavioral intervention that included automatic medication reminders and health tips, or to continue with usual care for 12 weeks. The primary outcome was mental distress, assessed using the SRQ-20 scale. Secondary outcomes included quality of life (measured with the SF-36 scale), adherence to diabetes self-care behaviors (assessed with the SCI-R scale), and HbA1c. An analysis of covariance model was used to evaluate the impact of the intervention on study outcomes. Between-group mean differences after the intervention period, adjusted for baseline data and relevant covariates, were reported, with statistical significance set at an alpha level of 0.05 Results: A total of 112 participants (63% female, 63% white; mean age: 72.5 years; mean T2D duration: 16.9 years; mean HbA1c: 7.9%) were randomized, with 103 completing the trial. At 12 weeks, participants in the intervention group showed a reduction in mental distress (mean difference: -1.46; 95% CI -2.73 to -0.19; p=0.024), an increase in quality of life (mean difference: 9.46; 95% CI 3.65 to 15.26; p=0.001), greater adherence to diabetes self-care behaviors (mean difference: 3.40; 95% CI 1.61 to 5.19; p&lt;0.001), and lower HbA1c (mean difference: -0.48; 95% CI -0.85 to -0.11; p=0.011) when compared to those in the usual care group Conclusion: In this randomized controlled trial, a smart-speaker-based intervention was associated with significant improvements in mental health, quality of life, diabetes self-care behaviors, and HbA1c in older adults with T2D Disclosure L.S. Matzenbacher: None. F.L. da Costa: None. L.G.B. de Barros: None. V. Gheno: None. I.S. Maia: None. L.M. Blank: None. M.B. Brum: None. L.F. Fontoura: None. J. Alessi: None. G.H. Telo: None. Funding Brazilian National Council for Scientific and Technological Development (CNPq/MCTI/FNDCT 18/2021 grant)","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"19 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144370516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NEDA RASOULI, ECENUR GUDER ARSLAN, ANDREI-MIRCEA CATARIG, KIM HOULIND, BERNHARD LUDVIK, JOAKIM NORDANSTIG, HARALD SOURIJ, SEBASTIAN THOMAS, SUBODH VERMA, MARC P. BONACA
Introduction and Objective: The STRIDE trial (NCT04560998) demonstrated that once weekly semaglutide 1.0 mg significantly improved maximum walking distance (MWD) in people with type 2 diabetes (T2D) and symptomatic peripheral artery disease (PAD) vs. placebo. Whether the benefits are consistent across T2D characteristics has not been described. Methods: The primary outcome in STRIDE, MWD measured on a constant load treadmill at 52 weeks, was analyzed by T2D duration (≥10 vs. <10 years), obesity status (BMI (≥30 vs. <30 kg/m2)), glycemic control (HbA1c (≥7% vs. <7%)), and concomitant T2D medications (SGLT2i or insulin). A mixed model for repeated measurements was employed, incorporating treatment, region, and subgroup as fixed factors, along with the treatment-by-subgroup interaction. Baseline values were used as covariates, all nested within each visit. Results: Among 792 randomized STRIDE participants at baseline, median T2D duration was 12.2 years, BMI 28.7 kg/m2, HbA1c 7.1%, with 35.1% on SGLT2i and 31.7% on insulin. Semaglutide significantly improved MWD regardless of T2D duration, BMI, HbA1c and concomitant SGLT2i or insulin use (Figure). Conclusion: These findings support the efficacy of semaglutide in patients with symptomatic PAD across the spectrum of T2D including non-obese participants and those with HbA1c <7%. Disclosure N. Rasouli: Advisory Panel; Novo Nordisk. Research Support; Novo Nordisk. Advisory Panel; Eli Lilly and Company. Research Support; Eli Lilly and Company. E. Guder Arslan: Employee; Novo Nordisk A/S, Sanofi. A. Catarig: Employee; Novo Nordisk A/S. Stock/Shareholder; Novo Nordisk A/S. K. Houlind: Consultant; LeMaitre, Novo Nordisk. B. Ludvik: Research Support; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Advisory Panel; Novo Nordisk, Boehringer-Ingelheim. Speaker's Bureau; Boehringer-Ingelheim. Research Support; Amgen Inc. Speaker's Bureau; AstraZeneca. Research Support; Eli Lilly and Company. Advisory Panel; Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. J. Nordanstig: Advisory Panel; AstraZeneca, Novo Nordisk. Other Relationship; Novo Nordisk. H. Sourij: Advisory Panel; Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. Research Support; Eli Lilly and Company. Advisory Panel; Boehringer-Ingelheim. Speaker's Bureau; Daiichi Sankyo. Advisory Panel; Novo Nordisk A/S. Speaker's Bureau; Novo Nordisk A/S. Advisory Panel; Novartis AG, Amarin Corporation, Amgen Inc. S. Thomas: None. S. Verma: Other Relationship; Various. M.P. Bonaca: Other Relationship; CPC Clinical Research. Funding The STRIDE trial was funded by Novo Nordisk A/S
STRIDE试验（NCT04560998）表明，与安慰剂相比，每周一次的semaglutide 1.0 mg可显著改善2型糖尿病（T2D）和症状性外周动脉疾病（PAD）患者的最大步行距离（MWD）。这些益处在T2D特征中是否一致尚未被描述。方法：STRIDE的主要终点，52周时在恒定负荷跑步机上测量的MWD，通过T2D持续时间（≥10 vs. <；10年）、肥胖状况（BMI(≥30 vs. <30 kg/m2)）、血糖控制(HbA1c（≥7% vs. <7%）和伴随的T2D药物（SGLT2i或胰岛素）进行分析。采用重复测量的混合模型，将治疗、地区和亚组作为固定因素，以及治疗与亚组之间的相互作用。基线值作为协变量，均嵌套在每次访问中。结果：在基线时792名STRIDE随机参与者中，T2D持续时间中位数为12.2年，BMI为28.7 kg/m2， HbA1c为7.1%，其中SGLT2i为35.1%，胰岛素为31.7%。无论t2dm持续时间、BMI、HbA1c和伴随的SGLT2i或胰岛素使用情况如何，Semaglutide都能显著改善MWD（图）。结论：这些发现支持了西马鲁肽对包括非肥胖和HbA1c≥7%的t2dm患者在内的有症状的PAD患者的疗效。N. Rasouli：顾问小组；诺和诺德公司。研究支持;诺和诺德公司。顾问小组;礼来公司。研究支持;礼来公司。E. Guder Arslan：雇员；诺和诺德公司，赛诺菲公司。A.配餐：员工；诺和诺德公司股票/股东;诺和诺德公司K. Houlind：顾问；LeMaitre，诺和诺德。B. Ludvik：研究支持；诺和诺德公司。演讲者的局;诺和诺德公司。顾问小组;诺和诺德，勃林格殷格翰。演讲者的局;勃林格殷格翰集团。研究支持;安进公司。演讲者的局;阿斯利康。研究支持;礼来公司。顾问小组;礼来公司。演讲者的局;礼来公司。J. Nordanstig：咨询小组；阿斯利康，诺和诺德。其他关系;诺和诺德公司。H. Sourij：咨询小组；礼来公司。演讲者的局;礼来公司。研究支持;礼来公司。顾问小组;勃林格殷格翰集团。演讲者的局;第一三共制药。顾问小组;诺和诺德公司演讲者的局;诺和诺德公司顾问小组;诺华公司、Amarin公司、安进公司托马斯：没有。S. Verma：其他关系；不同。博纳卡议员：其他关系；CPC临床研究。STRIDE试验由诺和诺德公司资助
{"title":"291-OR: Effect of Type 2 Diabetes Characteristics on Semaglutide Treatment in People with Type 2 Diabetes and Peripheral Artery Disease—A Post Hoc Analysis of the STRIDE Trial","authors":"NEDA RASOULI, ECENUR GUDER ARSLAN, ANDREI-MIRCEA CATARIG, KIM HOULIND, BERNHARD LUDVIK, JOAKIM NORDANSTIG, HARALD SOURIJ, SEBASTIAN THOMAS, SUBODH VERMA, MARC P. BONACA","doi":"10.2337/db25-291-or","DOIUrl":"https://doi.org/10.2337/db25-291-or","url":null,"abstract":"Introduction and Objective: The STRIDE trial (NCT04560998) demonstrated that once weekly semaglutide 1.0 mg significantly improved maximum walking distance (MWD) in people with type 2 diabetes (T2D) and symptomatic peripheral artery disease (PAD) vs. placebo. Whether the benefits are consistent across T2D characteristics has not been described. Methods: The primary outcome in STRIDE, MWD measured on a constant load treadmill at 52 weeks, was analyzed by T2D duration (≥10 vs. &lt;10 years), obesity status (BMI (≥30 vs. &lt;30 kg/m2)), glycemic control (HbA1c (≥7% vs. &lt;7%)), and concomitant T2D medications (SGLT2i or insulin). A mixed model for repeated measurements was employed, incorporating treatment, region, and subgroup as fixed factors, along with the treatment-by-subgroup interaction. Baseline values were used as covariates, all nested within each visit. Results: Among 792 randomized STRIDE participants at baseline, median T2D duration was 12.2 years, BMI 28.7 kg/m2, HbA1c 7.1%, with 35.1% on SGLT2i and 31.7% on insulin. Semaglutide significantly improved MWD regardless of T2D duration, BMI, HbA1c and concomitant SGLT2i or insulin use (Figure). Conclusion: These findings support the efficacy of semaglutide in patients with symptomatic PAD across the spectrum of T2D including non-obese participants and those with HbA1c &lt;7%. Disclosure N. Rasouli: Advisory Panel; Novo Nordisk. Research Support; Novo Nordisk. Advisory Panel; Eli Lilly and Company. Research Support; Eli Lilly and Company. E. Guder Arslan: Employee; Novo Nordisk A/S, Sanofi. A. Catarig: Employee; Novo Nordisk A/S. Stock/Shareholder; Novo Nordisk A/S. K. Houlind: Consultant; LeMaitre, Novo Nordisk. B. Ludvik: Research Support; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Advisory Panel; Novo Nordisk, Boehringer-Ingelheim. Speaker's Bureau; Boehringer-Ingelheim. Research Support; Amgen Inc. Speaker's Bureau; AstraZeneca. Research Support; Eli Lilly and Company. Advisory Panel; Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. J. Nordanstig: Advisory Panel; AstraZeneca, Novo Nordisk. Other Relationship; Novo Nordisk. H. Sourij: Advisory Panel; Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. Research Support; Eli Lilly and Company. Advisory Panel; Boehringer-Ingelheim. Speaker's Bureau; Daiichi Sankyo. Advisory Panel; Novo Nordisk A/S. Speaker's Bureau; Novo Nordisk A/S. Advisory Panel; Novartis AG, Amarin Corporation, Amgen Inc. S. Thomas: None. S. Verma: Other Relationship; Various. M.P. Bonaca: Other Relationship; CPC Clinical Research. Funding The STRIDE trial was funded by Novo Nordisk A/S","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"48 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction and Objective: A recent trial of tirzepatide (SURMOUNT) found a 92% reduction of diabetes incidence among patients with overweight or obesity over three years. Our objective was to estimate the potential population, outcomes, and cost associated with use of tirzepatide for the primary prevention of DM. Methods: Data from the 2021-2023 cycle of the National Health and Nutrition Examination Survey (NHANES) were used to estimate risk reductions for the incidence of DM extrapolated from SURMOUNT results. Costs and savings (from saved diabetes care costs) of tirzepatide were estimated under current U.S. list prices, direct to patient prices, and UK list prices. Results: In total, 2,022 NHANES participants were eligible for tirzepatide therapy (51% female, 49% male, median age 53, IQR 37-66) translating to a weighted U.S. population estimate of 83,454,492 (95% CI 74,423,832 - 92,485,151). Across the lifespan, 30,522,710 cases of diabetes could be prevented if risk reduction was persistent. Projected costs/savings are shown in Table 1. Conclusion: Nearly one in three Americans are potentially eligible for tirzepatide for the primary prevention of DM. At current list price, treating the entire population could cost nearly 20 trillion dollars, offset by only 3.4 trillion dollars of savings, yielding a net cost of approximately 16 trillion dollars, or 60% of 2023 US gross domestic product; treatment at the UK list price would result in nearly 500 billion in net savings. Disclosure J.B. Lusk: None. S. Aymes: None. E. OBrien: Research Support; Pfizer Inc. F. Li: None.
简介和目的：最近的一项试验发现，三年内，替西帕肽（SURMOUNT）可使超重或肥胖患者的糖尿病发病率降低92%。我们的目的是估计使用替西肽用于糖尿病一级预防的潜在人群、结局和成本。方法：使用来自2021-2023年国家健康与营养检查调查（NHANES）周期的数据来估计从SURMOUNT结果推断的糖尿病发病率的风险降低。替西帕肽的成本和节省（从节省的糖尿病护理费用中）是根据当前美国目录价格、直接对患者价格和英国目录价格估计的。结果：总共有2,022名NHANES参与者符合替西肽治疗的条件（51%女性，49%男性，中位年龄53岁，IQR 37-66），转化为加权的美国人口估计为83,454,492 （95% CI 74,423,832 - 92,485,151）。在整个生命周期中，如果风险持续降低，可以预防30,522,710例糖尿病病例。预计费用/节余见表1。结论：近三分之一的美国人可能有资格使用替西肽进行糖尿病的一级预防。按照目前的定价，治疗整个人群可能花费近20万亿美元，仅抵消3.4万亿美元的节省，产生约16万亿美元的净成本，或2023年美国国内生产总值的60%；按照英国的定价进行治疗将节省近5000亿英镑的净开支。J.B. Lusk：没有。S. Aymes：没有。E. brien：研究支持；辉瑞公司F.李：没有。
{"title":"173-OR: Eligibility, Impact, and Costs for Tirzepatide for the Primary Prevention of Diabetes Mellitus","authors":"JAY B. LUSK, SHANNON AYMES, EMILY OBRIEN, FAN LI","doi":"10.2337/db25-173-or","DOIUrl":"https://doi.org/10.2337/db25-173-or","url":null,"abstract":"Introduction and Objective: A recent trial of tirzepatide (SURMOUNT) found a 92% reduction of diabetes incidence among patients with overweight or obesity over three years. Our objective was to estimate the potential population, outcomes, and cost associated with use of tirzepatide for the primary prevention of DM. Methods: Data from the 2021-2023 cycle of the National Health and Nutrition Examination Survey (NHANES) were used to estimate risk reductions for the incidence of DM extrapolated from SURMOUNT results. Costs and savings (from saved diabetes care costs) of tirzepatide were estimated under current U.S. list prices, direct to patient prices, and UK list prices. Results: In total, 2,022 NHANES participants were eligible for tirzepatide therapy (51% female, 49% male, median age 53, IQR 37-66) translating to a weighted U.S. population estimate of 83,454,492 (95% CI 74,423,832 - 92,485,151). Across the lifespan, 30,522,710 cases of diabetes could be prevented if risk reduction was persistent. Projected costs/savings are shown in Table 1. Conclusion: Nearly one in three Americans are potentially eligible for tirzepatide for the primary prevention of DM. At current list price, treating the entire population could cost nearly 20 trillion dollars, offset by only 3.4 trillion dollars of savings, yielding a net cost of approximately 16 trillion dollars, or 60% of 2023 US gross domestic product; treatment at the UK list price would result in nearly 500 billion in net savings. Disclosure J.B. Lusk: None. S. Aymes: None. E. OBrien: Research Support; Pfizer Inc. F. Li: None.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"275 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ELIZABETH STATON, PIAOPIAO LI, JIEUN LEE, K M VENKAT NARAYAN, MOHAMMED K. ALI, ILANA GRAETZ, HUI SHAO
Introduction and Objective: GLP-1RA drugs have demonstrated benefits for people with type 2 diabetes mellitus (T2DM) or obesity, however, medication access is limited. This microsimulation study modeled the impact of increased access to semaglutide globally on the burden of 7 conditions. Methods: We developed and validated a microsimulation model incorporating age-, sex-, and country-specific prevalence and incidence data for T2DM, obesity, CVD, CKD, stroke, ESKD, and all-cause mortality, using data from the 2021 Global Burden of Disease and NCD-RisC studies. A simulation experiment was conducted to evaluate the effects of providing universal access to semaglutide on these key health outcomes over 5 years across 196 countries. Results: Of the worldwide adult population of approximately 6.1 billion, 19.0% met eligibility criteria for semaglutide use, based on a prevalence of 8.76% for type 2 diabetes and 16.4% for obesity. Universal access to semaglutide could reduce 5-year all-cause mortality by 7.41% (absolute change (AC): -0.29%, 95% CI: -0.47 to -0.10%; about 28M lives) and obesity prevalence by 21.9% (AC -5.42%, 95% CI: -6.48 to -4.36%; about 330M fewer obese individuals). Country specific results on all health outcomes are presented in Figure 1. Conclusion: Expanding access and affordability to GLP-1RA can significantly improve health worldwide. Disclosure E. Staton: None. P. Li: None. J. Lee: None. K. Narayan: None. M.K. Ali: Advisory Panel; Eli Lilly and Company. I. Graetz: Research Support; Pfizer Inc, PRIME Education, LLC. H. Shao: None. Funding National Institutes of Health (R01DK133465)
{"title":"2043-LB: Universal Access to GLP1-RAs Could Reduce Global Obesity Prevalence by 20% and Save 28 Million Lives over Five Years—A Microsimulation Study","authors":"ELIZABETH STATON, PIAOPIAO LI, JIEUN LEE, K M VENKAT NARAYAN, MOHAMMED K. ALI, ILANA GRAETZ, HUI SHAO","doi":"10.2337/db25-2043-lb","DOIUrl":"https://doi.org/10.2337/db25-2043-lb","url":null,"abstract":"Introduction and Objective: GLP-1RA drugs have demonstrated benefits for people with type 2 diabetes mellitus (T2DM) or obesity, however, medication access is limited. This microsimulation study modeled the impact of increased access to semaglutide globally on the burden of 7 conditions. Methods: We developed and validated a microsimulation model incorporating age-, sex-, and country-specific prevalence and incidence data for T2DM, obesity, CVD, CKD, stroke, ESKD, and all-cause mortality, using data from the 2021 Global Burden of Disease and NCD-RisC studies. A simulation experiment was conducted to evaluate the effects of providing universal access to semaglutide on these key health outcomes over 5 years across 196 countries. Results: Of the worldwide adult population of approximately 6.1 billion, 19.0% met eligibility criteria for semaglutide use, based on a prevalence of 8.76% for type 2 diabetes and 16.4% for obesity. Universal access to semaglutide could reduce 5-year all-cause mortality by 7.41% (absolute change (AC): -0.29%, 95% CI: -0.47 to -0.10%; about 28M lives) and obesity prevalence by 21.9% (AC -5.42%, 95% CI: -6.48 to -4.36%; about 330M fewer obese individuals). Country specific results on all health outcomes are presented in Figure 1. Conclusion: Expanding access and affordability to GLP-1RA can significantly improve health worldwide. Disclosure E. Staton: None. P. Li: None. J. Lee: None. K. Narayan: None. M.K. Ali: Advisory Panel; Eli Lilly and Company. I. Graetz: Research Support; Pfizer Inc, PRIME Education, LLC. H. Shao: None. Funding National Institutes of Health (R01DK133465)","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"36 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144335293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
JIA ZHAO, SHENGHUI LIANG, LILY GUO, MAJID MOJIBIAN, ROBERT K. BAKER, VIVIAN FUNG, MEGAN LEVINGS, ANDRAS NAGY, TIM KIEFFER
Introduction and Objective: Stem cell-derived islet (SC-islet) replacement therapies are currently being investigated in clinical trials and have shown great promise for diabetes treatment. However, challenges remain, including the use of chronic immunosuppressants to limit immune reactions to implanted cells. To address this issue, we hypothesize that genetically modifying stem cells to achieve localized immune evasion could enable functional and durable SC-islet engraftment in patients without systemic immunosuppression. Methods: A human embryonic stem cell (hESC) line was genetically modified with the goal of providing immune-evasiveness through the constitutive expression of transgenes encoding PD-L1, FASL, CD200, CD47, HLA-G, CCL21, SERPINB9 and MFGE8. An inducible kill switch was also integrated, whereby HSV-TK is linked to the cell division gene CDK1 such that dividing cells can be selectively eliminated by exposure to the pro-drug ganciclovir (GCV). Results: The genetically engineered hESCs efficiently differentiated into insulin-secreting SC-islets in vitro. When co-cultured with various immune cell types, these SC-islets suppressed immune cell activation and were resistant to immune cell-mediated killing. By individually antagonizing the immunomodulatory factors, we determined all eight contribute to such tolerance. When proliferation was induced in SC-islet cultures or SC-islets were purposely contaminated with undifferentiated stem cells, GCV treatment efficiently eliminated these dividing cells. Conclusion: Our data suggest that SC-islets engineered to overexpress these eight immunomodulatory factors enable immune evasion and the kill switch system is effective in removing proliferative cells present in cultures. Cell implant studies are underway to assess the immune-evasiveness and kill switch effectiveness in vivo. Ultimately, this approach could provide a universal source for SC-islets to treat diabetes without the use of immunosuppression. Disclosure J. Zhao: None. S. Liang: None. L. Guo: None. M. Mojibian: None. R.K. Baker: None. V. Fung: None. M. Levings: None. A. Nagy: None. T. Kieffer: Employee; Fractyl Health, Inc. Stock/Shareholder; Fractyl Health, Inc. Funding Breakthrough T1D (3-SRA-2022-1252-S-B)
{"title":"2139-LB: Immune-Shielded Islets from Engineered Human Pluripotent Stem Cells for Potential Allogeneic Therapy","authors":"JIA ZHAO, SHENGHUI LIANG, LILY GUO, MAJID MOJIBIAN, ROBERT K. BAKER, VIVIAN FUNG, MEGAN LEVINGS, ANDRAS NAGY, TIM KIEFFER","doi":"10.2337/db25-2139-lb","DOIUrl":"https://doi.org/10.2337/db25-2139-lb","url":null,"abstract":"Introduction and Objective: Stem cell-derived islet (SC-islet) replacement therapies are currently being investigated in clinical trials and have shown great promise for diabetes treatment. However, challenges remain, including the use of chronic immunosuppressants to limit immune reactions to implanted cells. To address this issue, we hypothesize that genetically modifying stem cells to achieve localized immune evasion could enable functional and durable SC-islet engraftment in patients without systemic immunosuppression. Methods: A human embryonic stem cell (hESC) line was genetically modified with the goal of providing immune-evasiveness through the constitutive expression of transgenes encoding PD-L1, FASL, CD200, CD47, HLA-G, CCL21, SERPINB9 and MFGE8. An inducible kill switch was also integrated, whereby HSV-TK is linked to the cell division gene CDK1 such that dividing cells can be selectively eliminated by exposure to the pro-drug ganciclovir (GCV). Results: The genetically engineered hESCs efficiently differentiated into insulin-secreting SC-islets in vitro. When co-cultured with various immune cell types, these SC-islets suppressed immune cell activation and were resistant to immune cell-mediated killing. By individually antagonizing the immunomodulatory factors, we determined all eight contribute to such tolerance. When proliferation was induced in SC-islet cultures or SC-islets were purposely contaminated with undifferentiated stem cells, GCV treatment efficiently eliminated these dividing cells. Conclusion: Our data suggest that SC-islets engineered to overexpress these eight immunomodulatory factors enable immune evasion and the kill switch system is effective in removing proliferative cells present in cultures. Cell implant studies are underway to assess the immune-evasiveness and kill switch effectiveness in vivo. Ultimately, this approach could provide a universal source for SC-islets to treat diabetes without the use of immunosuppression. Disclosure J. Zhao: None. S. Liang: None. L. Guo: None. M. Mojibian: None. R.K. Baker: None. V. Fung: None. M. Levings: None. A. Nagy: None. T. Kieffer: Employee; Fractyl Health, Inc. Stock/Shareholder; Fractyl Health, Inc. Funding Breakthrough T1D (3-SRA-2022-1252-S-B)","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"1 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144334851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
YU MI KANG, ROBERT P. GIUGLIANO, XINHUI RAN, PRAKASH DEEDWANIA, GAETANO M. DE FERRARI, JYOTHIS T. GEORGE, IOANNA GOUNI-BERTHOLD, GABRIEL PAIVA DA SILVA LIMA, YEHUDA HANDELSMAN, BASIL S. LEWIS, E. MAGNUS OHMAN, ANTHONY C. KEECH, HUEI WANG, MARC S. SABATINE, LAWRENCE A. LEITER
Introduction and Objective: Despite the very high risk for macrovascular complications, there are scant data on the benefit of lipid-lowering in type 1 diabetes (T1D). We examined the clinical efficacy of intensive LDL-C lowering with the PCSK9 inhibitor evolocumab in T1D. Methods: FOURIER enrolled pts w/ stable atherosclerotic cardiovascular disease (ASCVD) on statin randomized to evolocumab or placebo (median FU 2.2y). The primary endpoint (PEP) was CV death, MI, stroke, hospitalization for unstable angina, or coronary revascularization. The key secondary endpoint (SEP) was CV death, MI, or stroke. Hazard ratios (HR) and absolute risk reductions (ARR) with evolocumab vs. placebo were compared among pts w/o diabetes (no DM), with type 2 diabetes (T2D), and with T1D. Results: Of 27,564 pts, 197 (0.7%) had T1D. Their median (IQR) age was 58 (53-64) yrs and duration of diabetes 28 yrs. In the placebo arm, there was a stepwise increase in the 2.5-y KM rate of the PEP, going from 11.0% to 15.2% to 20.4% in pts w/ no DM, T2D, and T1D, respectively (p<0.0001; Fig). Evolocumab reduced the risk of the PEP by 13% (HR 0.87; 95% CI 0.73-0.96), 16% (HR 0.84 [0.75-0.93]), and 34% (HR 0.66 [0.32-1.38]), respectively. Corresponding ARRs were 1.3%, 2.5%, and 7.3%. Similar trends were seen for the key SEP. Conclusion: T1D pts with ASCVD face elevated MACE risk, and intensive LDL-C lowering with evolocumab appears to provide substantial clinical benefit in this high-risk group. Disclosure Y. Kang: None. R.P. Giugliano: Research Support; Amgen Inc, Anthos Therapeutics, Daiichi Sankyo, Ionis Pharmaceuticals. Other Relationship; Amgen Inc, CADECI, Centrix, Daiichi Sankyo, Dr. Reddy's Laboratories, Korean Heart Rhythm Society, Medical Education Resources (MER), Menarini, Pfizer Inc, SHAKEHEART, SUMMEET. Consultant; Amgen Inc, AstraZeneca, Beckman Coulter, Daiichi Sankyo, Gilead Sciences, Inc, Inventiva Pharma, Novartis Pharmaceuticals Corporation, Perosphere, Samsung, Syneos Health. X. Ran: None. P. Deedwania: None. G.M. De Ferrari: Advisory Panel; Daiichi Sankyo. Board Member; Amgen Inc, Merck & Co., Inc, Novartis AG. J.T. George: Employee; Amgen Inc. I. Gouni-Berthold: Speaker's Bureau; Amgen Inc, Sanofi-Aventis Deutschland GmbH. Advisory Panel; Daiichi Sankyo. Speaker's Bureau; Novartis AG. Advisory Panel; Novartis AG. Speaker's Bureau; Ultragenyx, Daiichi Sankyo. G. Paiva da Silva Lima: Employee; Amgen Inc. Stock/Shareholder; Amgen Inc. Y. Handelsman: Research Support; Amgen Inc. Consultant; Amgen Inc. Research Support; Applied Therapeutics. Consultant; Applied Therapeutics. Research Support; Corcept Therapeutics. Consultant; Corcept Therapeutics. Research Support; Ionis Pharmaceuticals, Lilly Diabetes, Merck Sharp & Dohme Corp, Regeneron Pharmaceuticals. B.S. Lewis: Consultant; Janssen Pharmaceuticals, Inc. E. Ohman: Employee; Amgen Inc. A.C. Keech: Research Support; Abbott, Amgen Inc, ASPEN Australia, Mylan. Speaker's Bureau; Novartis AG, Pfizer I
{"title":"1991-LB: Cardiovascular Efficacy of Evolocumab in Persons with Type 1 Diabetes Mellitus—Insights from FOURIER Trial","authors":"YU MI KANG, ROBERT P. GIUGLIANO, XINHUI RAN, PRAKASH DEEDWANIA, GAETANO M. DE FERRARI, JYOTHIS T. GEORGE, IOANNA GOUNI-BERTHOLD, GABRIEL PAIVA DA SILVA LIMA, YEHUDA HANDELSMAN, BASIL S. LEWIS, E. MAGNUS OHMAN, ANTHONY C. KEECH, HUEI WANG, MARC S. SABATINE, LAWRENCE A. LEITER","doi":"10.2337/db25-1991-lb","DOIUrl":"https://doi.org/10.2337/db25-1991-lb","url":null,"abstract":"Introduction and Objective: Despite the very high risk for macrovascular complications, there are scant data on the benefit of lipid-lowering in type 1 diabetes (T1D). We examined the clinical efficacy of intensive LDL-C lowering with the PCSK9 inhibitor evolocumab in T1D. Methods: FOURIER enrolled pts w/ stable atherosclerotic cardiovascular disease (ASCVD) on statin randomized to evolocumab or placebo (median FU 2.2y). The primary endpoint (PEP) was CV death, MI, stroke, hospitalization for unstable angina, or coronary revascularization. The key secondary endpoint (SEP) was CV death, MI, or stroke. Hazard ratios (HR) and absolute risk reductions (ARR) with evolocumab vs. placebo were compared among pts w/o diabetes (no DM), with type 2 diabetes (T2D), and with T1D. Results: Of 27,564 pts, 197 (0.7%) had T1D. Their median (IQR) age was 58 (53-64) yrs and duration of diabetes 28 yrs. In the placebo arm, there was a stepwise increase in the 2.5-y KM rate of the PEP, going from 11.0% to 15.2% to 20.4% in pts w/ no DM, T2D, and T1D, respectively (p&lt;0.0001; Fig). Evolocumab reduced the risk of the PEP by 13% (HR 0.87; 95% CI 0.73-0.96), 16% (HR 0.84 [0.75-0.93]), and 34% (HR 0.66 [0.32-1.38]), respectively. Corresponding ARRs were 1.3%, 2.5%, and 7.3%. Similar trends were seen for the key SEP. Conclusion: T1D pts with ASCVD face elevated MACE risk, and intensive LDL-C lowering with evolocumab appears to provide substantial clinical benefit in this high-risk group. Disclosure Y. Kang: None. R.P. Giugliano: Research Support; Amgen Inc, Anthos Therapeutics, Daiichi Sankyo, Ionis Pharmaceuticals. Other Relationship; Amgen Inc, CADECI, Centrix, Daiichi Sankyo, Dr. Reddy's Laboratories, Korean Heart Rhythm Society, Medical Education Resources (MER), Menarini, Pfizer Inc, SHAKEHEART, SUMMEET. Consultant; Amgen Inc, AstraZeneca, Beckman Coulter, Daiichi Sankyo, Gilead Sciences, Inc, Inventiva Pharma, Novartis Pharmaceuticals Corporation, Perosphere, Samsung, Syneos Health. X. Ran: None. P. Deedwania: None. G.M. De Ferrari: Advisory Panel; Daiichi Sankyo. Board Member; Amgen Inc, Merck & Co., Inc, Novartis AG. J.T. George: Employee; Amgen Inc. I. Gouni-Berthold: Speaker's Bureau; Amgen Inc, Sanofi-Aventis Deutschland GmbH. Advisory Panel; Daiichi Sankyo. Speaker's Bureau; Novartis AG. Advisory Panel; Novartis AG. Speaker's Bureau; Ultragenyx, Daiichi Sankyo. G. Paiva da Silva Lima: Employee; Amgen Inc. Stock/Shareholder; Amgen Inc. Y. Handelsman: Research Support; Amgen Inc. Consultant; Amgen Inc. Research Support; Applied Therapeutics. Consultant; Applied Therapeutics. Research Support; Corcept Therapeutics. Consultant; Corcept Therapeutics. Research Support; Ionis Pharmaceuticals, Lilly Diabetes, Merck Sharp & Dohme Corp, Regeneron Pharmaceuticals. B.S. Lewis: Consultant; Janssen Pharmaceuticals, Inc. E. Ohman: Employee; Amgen Inc. A.C. Keech: Research Support; Abbott, Amgen Inc, ASPEN Australia, Mylan. Speaker's Bureau; Novartis AG, Pfizer I","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"30 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144334849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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