Julieanne Knupp, Pedro Cardoso, Katherine G. Young, Timothy J. McDonald, Kashyap A. Patel, Kevin Colclough, Ewan R. Pearson, Angus G. Jones, Sophie Jones, Shivani Misra, Andrew T. Hattersley, Trevelyan J. McKinley, Beverley M. Shields
OBJECTIVE Selecting appropriate individuals for monogenic diabetes genetic testing is challenging. We aimed to develop a new probability calculator, integrating clinical features and biomarkers, to aid identification of monogenic diabetes. RESEARCH DESIGN AND METHODS We developed two prediction models (for early-insulin-treated, proxy for type 1 diabetes; and not-early-insulin-treated patients, proxy for type 2 diabetes) using a Bayesian recalibration mixture model approach. We used case-control data (monogenic diabetes = 594, non-monogenic diabetes = 597) for initial model development (clinical features only) and recalibrated to population data (Using pharmacogeNetics to Improve Treatment in Early-onset Diabetes [UNITED] study, n = 1,299) including biomarkers (C-peptide and islet autoantibodies). We externally validated the calculator in an independent population-based cohort (n = 1,025). RESULTS For early-insulin-treated individuals, the model incorporating biomarkers improved discrimination over using clinical features only (Receiver Operating Characteristic Area Under the Curve [ROCAUC] 0.98 [95% credible interval [CrI] 0.95–0.98] vs. 0.80 [95% CrI 0.71–0.82], P < 0.001) or biomarkers alone (ROCAUC 0.96 [95% CI 0.95–0.97]). For not-early-insulin-treated participants, the calculator showed good discrimination (ROCAUC 0.86 [95% CrI 0.85–0.88]). Both models calibrated well and showed good discrimination in external validation (ROCAUC 0.98 [95% CrI 0.98-0.98] and 0.92 [95% CrI 0.90-0.93] for early- and not-early-insulin-treated individuals, respectively). Using a ≥5% probability threshold to guide testing achieved positive test rates for monogenic diabetes of 16–19%. CONCLUSIONS We developed an updated monogenic diabetes probability calculator that integrates both clinical features and biomarkers, providing greater discrimination than using clinical features or biomarkers alone and providing appropriate measures for selecting individuals for monogenic diabetes diagnostic testing. This is now available as an online calculator and has immediate clinical utility for White European individuals diagnosed with diabetes ≤35 years.
目的选择合适的个体进行单基因糖尿病基因检测具有挑战性。我们的目标是开发一个新的概率计算器，整合临床特征和生物标志物，以帮助识别单基因糖尿病。研究设计和方法我们使用贝叶斯再校准混合模型方法建立了两种预测模型（早期胰岛素治疗患者，代表1型糖尿病；和未早期胰岛素治疗患者，代表2型糖尿病）。我们使用病例对照数据（单基因糖尿病= 594，非单基因糖尿病= 597）进行初始模型开发（仅临床特征），并重新校准为人群数据（使用药物遗传学来改善早发性糖尿病的治疗[UNITED]研究，n = 1,299），包括生物标志物（c肽和胰岛自身抗体）。我们在一个独立的基于人群的队列（n = 1,025）中对计算器进行了外部验证。结果：对于早期接受胰岛素治疗的个体，纳入生物标志物的模型比仅使用临床特征（受试者工作特征曲线下面积[ROCAUC] 0.98[95%可信区间[CrI] 0.95-0.98] vs. 0.80[95%可信区间[CrI] 0.71-0.82], P < 0.001）或单独使用生物标志物（ROCAUC 0.96 [95% CI 0.95-0.97]）改善了识别。对于未早期接受胰岛素治疗的受试者，该计算器显示出良好的辨别能力（ROCAUC 0.86 [95% CrI 0.85-0.88]）。两种模型都校准良好，并在外部验证中表现出良好的辨别能力（早期和非早期胰岛素治疗个体的ROCAUC分别为0.98 [95% CrI 0.98-0.98]和0.92 [95% CrI 0.90-0.93]）。使用≥5%的概率阈值来指导检测，单基因糖尿病的阳性检测率为16-19%。结论：我们开发了一种更新的单基因糖尿病概率计算器，它集成了临床特征和生物标志物，比单独使用临床特征或生物标志物提供了更大的辨别能力，并为选择个体进行单基因糖尿病诊断检测提供了适当的措施。现在，这是一个在线计算器，对诊断为糖尿病≤35岁的欧洲白人具有直接的临床效用。
{"title":"Updating a Clinical Prediction Model for Identifying Monogenic Diabetes to Include Both Clinical Features and Biomarkers","authors":"Julieanne Knupp, Pedro Cardoso, Katherine G. Young, Timothy J. McDonald, Kashyap A. Patel, Kevin Colclough, Ewan R. Pearson, Angus G. Jones, Sophie Jones, Shivani Misra, Andrew T. Hattersley, Trevelyan J. McKinley, Beverley M. Shields","doi":"10.2337/dc25-1029","DOIUrl":"https://doi.org/10.2337/dc25-1029","url":null,"abstract":"OBJECTIVE Selecting appropriate individuals for monogenic diabetes genetic testing is challenging. We aimed to develop a new probability calculator, integrating clinical features and biomarkers, to aid identification of monogenic diabetes. RESEARCH DESIGN AND METHODS We developed two prediction models (for early-insulin-treated, proxy for type 1 diabetes; and not-early-insulin-treated patients, proxy for type 2 diabetes) using a Bayesian recalibration mixture model approach. We used case-control data (monogenic diabetes = 594, non-monogenic diabetes = 597) for initial model development (clinical features only) and recalibrated to population data (Using pharmacogeNetics to Improve Treatment in Early-onset Diabetes [UNITED] study, n = 1,299) including biomarkers (C-peptide and islet autoantibodies). We externally validated the calculator in an independent population-based cohort (n = 1,025). RESULTS For early-insulin-treated individuals, the model incorporating biomarkers improved discrimination over using clinical features only (Receiver Operating Characteristic Area Under the Curve [ROCAUC] 0.98 [95% credible interval [CrI] 0.95–0.98] vs. 0.80 [95% CrI 0.71–0.82], P &lt; 0.001) or biomarkers alone (ROCAUC 0.96 [95% CI 0.95–0.97]). For not-early-insulin-treated participants, the calculator showed good discrimination (ROCAUC 0.86 [95% CrI 0.85–0.88]). Both models calibrated well and showed good discrimination in external validation (ROCAUC 0.98 [95% CrI 0.98-0.98] and 0.92 [95% CrI 0.90-0.93] for early- and not-early-insulin-treated individuals, respectively). Using a ≥5% probability threshold to guide testing achieved positive test rates for monogenic diabetes of 16–19%. CONCLUSIONS We developed an updated monogenic diabetes probability calculator that integrates both clinical features and biomarkers, providing greater discrimination than using clinical features or biomarkers alone and providing appropriate measures for selecting individuals for monogenic diabetes diagnostic testing. This is now available as an online calculator and has immediate clinical utility for White European individuals diagnosed with diabetes ≤35 years.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"27 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145289228","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}
Cyrielle Caussy, Kenneth Cusi, Julio Rosenstock, Elisabetta Bugianesi, Melissa K. Thomas, Yuanyuan Tang, Kieren J. Mather, Rohit Loomba, Arun J. Sanyal, Mark L. Hartman
OBJECTIVE To explore the relationship between metabolic and histological responses in a phase 2 trial of tirzepatide in metabolic dysfunction–associated steatohepatitis (MASH). RESEARCH DESIGN AND METHODS This is a participant-level post hoc analysis of the 52-week, double-blind, randomized, placebo-controlled SYNERGY-NASH trial (NCT04166773). Participants (n = 190) with MASH and stage 2/3 fibrosis were randomly assigned to receive tirzepatide (5, 10, or 15 mg) or placebo once weekly. The primary end point was MASH resolution without worsening of fibrosis. Secondary end points included fibrosis improvement by at least one stage without worsening of MASH. Metabolic changes were evaluated in responders and nonresponders for histological end points in 154 participants who completed the study on treatment. RESULTS At baseline, 59% had type 2 diabetes and mean BMI was 35.7 kg/m2. Compared with nonresponders, greater body weight reductions were observed in responders for MASH resolution (−16.0% vs. −7.0%; P < 0.001) and for fibrosis improvement (−13.6% vs. −9.8%; P = 0.023). Reductions in HbA1c were greater for MASH responders (−1.2% vs. −0.6%; P < 0.001) and fibrosis responders (−1.2% vs. −0.7%; P = 0.004) than for nonresponders. Compared with nonresponders, greater improvements in liver fat and measures of adipose tissue insulin sensitivity (adipose tissue insulin resistance index and adiponectin) were observed with MASH responders (P < 0.001). In causal mediation analyses, normalization of liver fat was a significant mediator of both MASH resolution and fibrosis improvement. CONCLUSIONS In this post hoc exploratory analysis, MASH resolution and fibrosis improvement were associated with body weight reduction, improved glycemic control, and normalization of liver fat. Weight reduction and metabolic improvements with tirzepatide treatment potentially contributed to disease modification in MASH.
目的探讨替西肽治疗代谢功能障碍相关性脂肪性肝炎（MASH）的2期临床试验中代谢和组织学反应之间的关系。研究设计和方法：这是一项为期52周、双盲、随机、安慰剂对照的SYNERGY-NASH试验（NCT04166773）的参与者水平的事后分析。患有MASH和2/3期纤维化的参与者（n = 190）被随机分配接受替西帕肽（5、10或15 mg）或安慰剂，每周一次。主要终点为无纤维化恶化的MASH消退。次要终点包括纤维化改善至少一个阶段，无MASH恶化。对154名完成治疗研究的参与者进行组织学终点的代谢变化评估。结果：基线时，59%的患者患有2型糖尿病，平均BMI为35.7 kg/m2。与无应答者相比，应答者的体重减轻幅度更大，在MASH消退（- 16.0% vs - 7.0%; P < 0.001）和纤维化改善（- 13.6% vs - 9.8%; P = 0.023）。与无应答者相比，MASH应答者（- 1.2% vs. - 0.6%; P < 0.001）和纤维化应答者（- 1.2% vs. - 0.7%; P = 0.004）的HbA1c降低幅度更大。与无应答者相比，肝脏脂肪和脂肪组织胰岛素敏感性（脂肪组织胰岛素抵抗指数和脂联素）的改善更大（P < 0.001）。在因果中介分析中，肝脂肪的正常化是MASH解决和纤维化改善的重要中介。结论：在这项事后探索性分析中，MASH解决和纤维化改善与体重减轻、血糖控制改善和肝脂肪正常化相关。替西帕肽治疗的体重减轻和代谢改善可能有助于MASH的疾病改善。
{"title":"Relationship Between Metabolic and Histological Responses in People With Metabolic Dysfunction-Associated Steatohepatitis With and Without Type 2 Diabetes: Participant-Level Exploratory Analysis of the SYNERGY-NASH Trial With Tirzepatide","authors":"Cyrielle Caussy, Kenneth Cusi, Julio Rosenstock, Elisabetta Bugianesi, Melissa K. Thomas, Yuanyuan Tang, Kieren J. Mather, Rohit Loomba, Arun J. Sanyal, Mark L. Hartman","doi":"10.2337/dc25-1306","DOIUrl":"https://doi.org/10.2337/dc25-1306","url":null,"abstract":"OBJECTIVE To explore the relationship between metabolic and histological responses in a phase 2 trial of tirzepatide in metabolic dysfunction–associated steatohepatitis (MASH). RESEARCH DESIGN AND METHODS This is a participant-level post hoc analysis of the 52-week, double-blind, randomized, placebo-controlled SYNERGY-NASH trial (NCT04166773). Participants (n = 190) with MASH and stage 2/3 fibrosis were randomly assigned to receive tirzepatide (5, 10, or 15 mg) or placebo once weekly. The primary end point was MASH resolution without worsening of fibrosis. Secondary end points included fibrosis improvement by at least one stage without worsening of MASH. Metabolic changes were evaluated in responders and nonresponders for histological end points in 154 participants who completed the study on treatment. RESULTS At baseline, 59% had type 2 diabetes and mean BMI was 35.7 kg/m2. Compared with nonresponders, greater body weight reductions were observed in responders for MASH resolution (−16.0% vs. −7.0%; P &lt; 0.001) and for fibrosis improvement (−13.6% vs. −9.8%; P = 0.023). Reductions in HbA1c were greater for MASH responders (−1.2% vs. −0.6%; P &lt; 0.001) and fibrosis responders (−1.2% vs. −0.7%; P = 0.004) than for nonresponders. Compared with nonresponders, greater improvements in liver fat and measures of adipose tissue insulin sensitivity (adipose tissue insulin resistance index and adiponectin) were observed with MASH responders (P &lt; 0.001). In causal mediation analyses, normalization of liver fat was a significant mediator of both MASH resolution and fibrosis improvement. CONCLUSIONS In this post hoc exploratory analysis, MASH resolution and fibrosis improvement were associated with body weight reduction, improved glycemic control, and normalization of liver fat. Weight reduction and metabolic improvements with tirzepatide treatment potentially contributed to disease modification in MASH.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"26 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145255686","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}
Allison Ducharme-Smith, Michael Juntunen, Anna Espinoza, Chad Liedl, Karen Fischer, Angela Meilander, Jaxon Quillen, Rozalina G. McCoy
OBJECTIVE To evaluate the impact of community paramedic (CP)-delivered, in-home diabetes self-management education and support (DSMES) for adults with poorly managed diabetes. RESEARCH DESIGN AND METHODS In a pragmatic, single-arm pilot trial, adults with HbA1c ≥9% and a recent emergency department or hospital visit received a 1-month CP-led DSMES intervention. Outcomes included HbA1c, health care engagement, and patient-reported satisfaction. RESULTS Seventy participants (median age 61 years, 50% rural, 84% with type 2 diabetes) completed the intervention. HbA1c declined from 9.8 to 8.2% at 4 months (P < 0.001). Engagement with primary care, endocrinology, and DSMES improved. Satisfaction was high (mean rating 9 out of 10). CONCLUSIONS CP-led DSMES improved glycemic management and care engagement in underserved populations. This scalable model warrants further study.
{"title":"Pilot Pragmatic Trial of a Community Paramedic Diabetes Self-Management Education Program for Adults With Diabetes","authors":"Allison Ducharme-Smith, Michael Juntunen, Anna Espinoza, Chad Liedl, Karen Fischer, Angela Meilander, Jaxon Quillen, Rozalina G. McCoy","doi":"10.2337/dc25-1580","DOIUrl":"https://doi.org/10.2337/dc25-1580","url":null,"abstract":"OBJECTIVE To evaluate the impact of community paramedic (CP)-delivered, in-home diabetes self-management education and support (DSMES) for adults with poorly managed diabetes. RESEARCH DESIGN AND METHODS In a pragmatic, single-arm pilot trial, adults with HbA1c ≥9% and a recent emergency department or hospital visit received a 1-month CP-led DSMES intervention. Outcomes included HbA1c, health care engagement, and patient-reported satisfaction. RESULTS Seventy participants (median age 61 years, 50% rural, 84% with type 2 diabetes) completed the intervention. HbA1c declined from 9.8 to 8.2% at 4 months (P &lt; 0.001). Engagement with primary care, endocrinology, and DSMES improved. Satisfaction was high (mean rating 9 out of 10). CONCLUSIONS CP-led DSMES improved glycemic management and care engagement in underserved populations. This scalable model warrants further study.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"57 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145241706","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}
Xinyu Shu, Juan Juan, Mi Yao, Chenglong Li, Xin Kang, Xu Chen, Zhuo Wei, Lingyi Kong, Haitian Chen, Shihong Cui, Fengchun Gao, Ping Zhu, Jianying Yan, Xia Xu, Li Zhang, Yanxia Wang, Yang Mi, Huixia Yang
OBJECTIVE To examine whether glycemic level modifies the association between gestational weight gain (GWG) and pregnant outcomes in type 2 diabetes–complicated pregnancies. RESEARCH DESIGN AND METHODS This multicenter retrospective study stratified 1,642 pregnant women with diabetes by third-trimester glycemic control. Associations between excessive GWG (eGWG) and pregnant outcomes were analyzed by group. RESULTS Although birth weight and odds of macrosomia and cesarean delivery were higher for all women with eGWG relative to those with adequate GWG, the effect estimates for birth weight and macrosomia were significantly higher with suboptimal glycemic control compared with optimal control (birth weight increase: 361.04 vs. 126.07 g, respectively, P = 0.007; adjusted odds ratio for macrosomia: 4.26 vs. 2.73, P = 0.002; cesarean delivery: 1.86 vs. 1.52, P = 0.738). CONCLUSIONS Overly stringent weight control should be treated with caution if optimal glycemic control is not achieved.
目的探讨血糖水平是否改变2型糖尿病合并妊娠妊娠体重增加（GWG）与妊娠结局之间的关系。研究设计和方法：本多中心回顾性研究对1642例妊娠晚期糖尿病孕妇进行血糖控制分层。按组分析孕产GWG （eGWG）过高与妊娠结局的关系。结果：尽管与GWG充足的孕妇相比，所有eGWG患者的出生体重、巨大儿和剖宫产的几率更高，但与最佳血糖控制相比，次优血糖控制对出生体重和巨大儿的影响估计显著更高（出生体重增加：分别为361.04和126.07 g, P = 0.007；巨大儿的调整优势比：4.26比2.73,P = 0.002；剖宫产：1.86比1.52,P = 0.738）。结论：如果不能达到最佳血糖控制，应谨慎对待过于严格的体重控制。
{"title":"Glycemic Level Modifies the Relationship Between Maternal Gestational Weight Gain and Neonatal Birth Weight in Type 2 Diabetes–Complicated Pregnancies","authors":"Xinyu Shu, Juan Juan, Mi Yao, Chenglong Li, Xin Kang, Xu Chen, Zhuo Wei, Lingyi Kong, Haitian Chen, Shihong Cui, Fengchun Gao, Ping Zhu, Jianying Yan, Xia Xu, Li Zhang, Yanxia Wang, Yang Mi, Huixia Yang","doi":"10.2337/dc25-1086","DOIUrl":"https://doi.org/10.2337/dc25-1086","url":null,"abstract":"OBJECTIVE To examine whether glycemic level modifies the association between gestational weight gain (GWG) and pregnant outcomes in type 2 diabetes–complicated pregnancies. RESEARCH DESIGN AND METHODS This multicenter retrospective study stratified 1,642 pregnant women with diabetes by third-trimester glycemic control. Associations between excessive GWG (eGWG) and pregnant outcomes were analyzed by group. RESULTS Although birth weight and odds of macrosomia and cesarean delivery were higher for all women with eGWG relative to those with adequate GWG, the effect estimates for birth weight and macrosomia were significantly higher with suboptimal glycemic control compared with optimal control (birth weight increase: 361.04 vs. 126.07 g, respectively, P = 0.007; adjusted odds ratio for macrosomia: 4.26 vs. 2.73, P = 0.002; cesarean delivery: 1.86 vs. 1.52, P = 0.738). CONCLUSIONS Overly stringent weight control should be treated with caution if optimal glycemic control is not achieved.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"72 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145203254","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}
Binkai Liu, Yeli Wang, Yang Hu, Yi Wan, Cuilin Zhang, Eric B. Rimm, Frank B. Hu, Qi Sun
OBJECTIVE To prospectively examine associations between five low-carbohydrate diets (LCDs), differentiated by macronutrient quality, and type 2 diabetes (T2D) risk. RESEARCH DESIGN AND METHODS This cohort study included 199,006 U.S. adults from the Nurses’ Health Study (NHS) (1984–2018), NHSII (1991–2019), and Health Professionals Follow-up Study (1986–2018); free of T2D, cardiovascular disease, and cancer at baseline; and followed over 30 years. Diet was assessed every 2–4 years using validated food frequency questionnaires since baseline. Five LCD scores were derived based on intakes of protein, fat, and carbohydrates from contrasting food sources. The primary outcome was incident T2D. RESULTS During 4,987,761 person-years of follow-up, 20,452 T2D cases were documented. After adjustments for baseline BMI and other covariates, higher overall LCD score was associated with higher T2D risk (hazard ratio comparing highest vs. lowest quintile 1.31 [95% CI 1.25–1.37]; P-trend < 0.001). An animal-based LCD emphasizing animal protein and fat and an unhealthy LCD score further deemphasizing whole grains and other high-quality carbohydrates were associated with higher T2D risk (1.39 [1.32–1.45] and 1.44 [1.37–1.51]; both P-trend < 0.001). In contrast, a vegetable-based LCD emphasizing plant protein and fat was associated with a 6% lower T2D risk (0.94 [0.90–0.98]; P-trend = 0.004), and a healthy LCD further deemphasizing refined carbohydrates was associated with a 16% lower T2D risk (0.84 [0.81–0.88]; P-trend < 0.001]). Associations for overall, animal-based, and unhealthy LCDs were stronger among participants with lower baseline BMI and were partially mediated by weight change. CONCLUSIONS LCDs may not be beneficial for primary prevention of T2D unless they prioritize plant-based protein, healthy fats, and high-quality carbohydrates.
{"title":"Low-Carbohydrate Diets of Varying Macronutrient Quality and Risk of Type 2 Diabetes in Three U.S. Prospective Cohort Studies","authors":"Binkai Liu, Yeli Wang, Yang Hu, Yi Wan, Cuilin Zhang, Eric B. Rimm, Frank B. Hu, Qi Sun","doi":"10.2337/dc25-1401","DOIUrl":"https://doi.org/10.2337/dc25-1401","url":null,"abstract":"OBJECTIVE To prospectively examine associations between five low-carbohydrate diets (LCDs), differentiated by macronutrient quality, and type 2 diabetes (T2D) risk. RESEARCH DESIGN AND METHODS This cohort study included 199,006 U.S. adults from the Nurses’ Health Study (NHS) (1984–2018), NHSII (1991–2019), and Health Professionals Follow-up Study (1986–2018); free of T2D, cardiovascular disease, and cancer at baseline; and followed over 30 years. Diet was assessed every 2–4 years using validated food frequency questionnaires since baseline. Five LCD scores were derived based on intakes of protein, fat, and carbohydrates from contrasting food sources. The primary outcome was incident T2D. RESULTS During 4,987,761 person-years of follow-up, 20,452 T2D cases were documented. After adjustments for baseline BMI and other covariates, higher overall LCD score was associated with higher T2D risk (hazard ratio comparing highest vs. lowest quintile 1.31 [95% CI 1.25–1.37]; P-trend &lt; 0.001). An animal-based LCD emphasizing animal protein and fat and an unhealthy LCD score further deemphasizing whole grains and other high-quality carbohydrates were associated with higher T2D risk (1.39 [1.32–1.45] and 1.44 [1.37–1.51]; both P-trend &lt; 0.001). In contrast, a vegetable-based LCD emphasizing plant protein and fat was associated with a 6% lower T2D risk (0.94 [0.90–0.98]; P-trend = 0.004), and a healthy LCD further deemphasizing refined carbohydrates was associated with a 16% lower T2D risk (0.84 [0.81–0.88]; P-trend &lt; 0.001]). Associations for overall, animal-based, and unhealthy LCDs were stronger among participants with lower baseline BMI and were partially mediated by weight change. CONCLUSIONS LCDs may not be beneficial for primary prevention of T2D unless they prioritize plant-based protein, healthy fats, and high-quality carbohydrates.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"72 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145195380","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}
Aaron N. Winn, Zachary Newman, Amber Deckard, Melissa I. Franco-Galicia, Erin M. Staab, Monica E. Peek, Anirban Basu, Philip Clarke, Wen Wan, Elbert S. Huang, Andrew J. Karter, Donald Miller, M. Reza Skandari, Howard H. Moffet, Mengqi Zhu, Jennifer Y. Liu, Jyoti Sarker, Wael Mohammed, Robert Smith, Neda Laiteerapong
OBJECTIVE The objective of this study was to develop and internally validate a mathematical model of the relationships between patient clinical and social risk factors and outcomes using data from a multiethnic population with type 2 diabetes. RESEARCH DESIGN AND METHODS We constructed an incidence cohort of all adults (18 years or older) with newly diagnosed type 2 diabetes in the Kaiser Permanente Northern California (KPNC) health care system between 2005 and 2016 (n = 129,000), following patients for at least 1 year, but up to 12 years. Using this cohort, we modeled 17 distinct diabetes-related outcomes related to micro- and macrovascular disease, as well as atrial fibrillation, depression, dementia, relevant biomarkers, and mortality. RESULTS Data were randomly split into 50%, 25%, and 25% samples to perform model estimation, calibration, and validation, respectively. Empirical and simulated data were similar for the events and biomarkers, but some factors required calibration. After calibration, they closely aligned with empirical estimates. CONCLUSIONS The resulting Diabetes Outcome Model of the U.S. (DOMUS) is a major step forward in understanding diabetes progression and the role of social determinants of health. This model can be used by scientists, policymakers, and health system managers to better understand how choices can affect population health and health disparities, including the broad diversity of U.S. races and ethnicities. Moreover, this model can be used to realize longer-term comparative effectiveness in cost-effectiveness analyses for diabetes management in the future.
{"title":"Development and Internal Validation of the Multiethnic Type 2 Diabetes Outcomes Model for the U.S. (DOMUS)","authors":"Aaron N. Winn, Zachary Newman, Amber Deckard, Melissa I. Franco-Galicia, Erin M. Staab, Monica E. Peek, Anirban Basu, Philip Clarke, Wen Wan, Elbert S. Huang, Andrew J. Karter, Donald Miller, M. Reza Skandari, Howard H. Moffet, Mengqi Zhu, Jennifer Y. Liu, Jyoti Sarker, Wael Mohammed, Robert Smith, Neda Laiteerapong","doi":"10.2337/dc25-0911","DOIUrl":"https://doi.org/10.2337/dc25-0911","url":null,"abstract":"OBJECTIVE The objective of this study was to develop and internally validate a mathematical model of the relationships between patient clinical and social risk factors and outcomes using data from a multiethnic population with type 2 diabetes. RESEARCH DESIGN AND METHODS We constructed an incidence cohort of all adults (18 years or older) with newly diagnosed type 2 diabetes in the Kaiser Permanente Northern California (KPNC) health care system between 2005 and 2016 (n = 129,000), following patients for at least 1 year, but up to 12 years. Using this cohort, we modeled 17 distinct diabetes-related outcomes related to micro- and macrovascular disease, as well as atrial fibrillation, depression, dementia, relevant biomarkers, and mortality. RESULTS Data were randomly split into 50%, 25%, and 25% samples to perform model estimation, calibration, and validation, respectively. Empirical and simulated data were similar for the events and biomarkers, but some factors required calibration. After calibration, they closely aligned with empirical estimates. CONCLUSIONS The resulting Diabetes Outcome Model of the U.S. (DOMUS) is a major step forward in understanding diabetes progression and the role of social determinants of health. This model can be used by scientists, policymakers, and health system managers to better understand how choices can affect population health and health disparities, including the broad diversity of U.S. races and ethnicities. Moreover, this model can be used to realize longer-term comparative effectiveness in cost-effectiveness analyses for diabetes management in the future.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"89 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145141547","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}
OBJECTIVE Newborns delivered by women with gestational diabetes mellitus (GDM) have accelerated intrauterine growth earlier than the current recommended screening period. We aimed to determine whether universal GDM screening using a single oral glucose intolerance test (OGTT) at 18–20 weeks’ gestation improves pregnancy outcomes compared with standard screening at 24–28 weeks’ gestation. RESEARCH DESIGN AND METHODS We conducted a dual-center, parallel, randomized controlled trial with a planned interim analysis in singleton pregnant women to compare the effect of midpregnancy screening for GDM at 18–20 weeks’ gestation and standard screening at 24–28 weeks’ gestation. GDM was universally screened and diagnosed using 75-g OGTTs and the International Association of the Diabetes and Pregnancy Study Groups criteria. The primary outcome was a composite measure of primary cesarean delivery, birth weight >90th percentile, neonatal hypoglycemia, cord serum C-peptide >90th percentile, gestational hypertension, preeclampsia, and birth trauma. RESULTS The trial was stopped early for futility after the interim analysis. Of the 967 women included in the intention-to-treat analysis, the primary outcome was not significantly different between the two groups. Neonatal hypoglycemia was significantly lower and neonatal adiposity in women with GDM was higher in the midpregnancy screening group compared with the standard screening group. Adverse event rates were similar between the two groups. CONCLUSIONS Advancing universal GDM screening to midpregnancy at 18–20 weeks’ gestation may not improve pregnancy outcomes, except for a reduction in neonatal hypoglycemia. Newborns of women diagnosed with GDM through midpregnancy screening had higher neonatal adiposity.
{"title":"The Effect of Midpregnancy Screening for Gestational Diabetes Mellitus on Pregnancy Outcomes: The TESGO Randomized Controlled Trial","authors":"Chun-Heng Kuo, Ming-Wei Lin, Szu-Chieh Chen, I-Weng Yen, Kang-Chih Fan, Chih-Yao Hsu, Chien-Nan Lee, Chin-Hao Chang, Yu-Han Chang, Yi-Yun Tai, Chin-Ho Cheng, Kuan-Ying Huang, Wen-Wei Hsu, Jessica Kang, Jin-Chung Shih, Ming-Hua Ho, Tzu-Yi Chen, Shin-Yu Lin, Hung-Yuan Li","doi":"10.2337/dc25-0084","DOIUrl":"https://doi.org/10.2337/dc25-0084","url":null,"abstract":"OBJECTIVE Newborns delivered by women with gestational diabetes mellitus (GDM) have accelerated intrauterine growth earlier than the current recommended screening period. We aimed to determine whether universal GDM screening using a single oral glucose intolerance test (OGTT) at 18–20 weeks’ gestation improves pregnancy outcomes compared with standard screening at 24–28 weeks’ gestation. RESEARCH DESIGN AND METHODS We conducted a dual-center, parallel, randomized controlled trial with a planned interim analysis in singleton pregnant women to compare the effect of midpregnancy screening for GDM at 18–20 weeks’ gestation and standard screening at 24–28 weeks’ gestation. GDM was universally screened and diagnosed using 75-g OGTTs and the International Association of the Diabetes and Pregnancy Study Groups criteria. The primary outcome was a composite measure of primary cesarean delivery, birth weight &gt;90th percentile, neonatal hypoglycemia, cord serum C-peptide &gt;90th percentile, gestational hypertension, preeclampsia, and birth trauma. RESULTS The trial was stopped early for futility after the interim analysis. Of the 967 women included in the intention-to-treat analysis, the primary outcome was not significantly different between the two groups. Neonatal hypoglycemia was significantly lower and neonatal adiposity in women with GDM was higher in the midpregnancy screening group compared with the standard screening group. Adverse event rates were similar between the two groups. CONCLUSIONS Advancing universal GDM screening to midpregnancy at 18–20 weeks’ gestation may not improve pregnancy outcomes, except for a reduction in neonatal hypoglycemia. Newborns of women diagnosed with GDM through midpregnancy screening had higher neonatal adiposity.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"99 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145127770","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}
Rajiv Agarwal, Jennifer B. Green, Hiddo J.L. Heerspink, Johannes F.E. Mann, Janet B. McGill, Amy K. Mottl, Masaomi Nangaku, Julio Rosenstock, Muthiah Vaduganathan, Meike Brinker, Charlie Scott, Li Li, Na Li, Katja Rohwedder, Peter Rossing
OBJECTIVE The CONFIDENCE trial demonstrated additive benefits of simultaneous initiation of finerenone, a nonsteroidal mineralocorticoid receptor antagonist, and a sodium–glucose cotransporter 2 (SGLT2) inhibitor compared with monotherapy in reducing the urinary albumin-to-creatinine ratio (UACR). This prespecified analysis evaluated whether safety and efficacy of combination therapy varies by baseline glucagon-like peptide 1 receptor agonist (GLP-1 RA) use. RESEARCH DESIGN AND METHODS Adults with chronic kidney disease (UACR ≥100 to <5,000 mg/g; estimated glomerular filtration rate [eGFR] 30–90 mL/min/1.73 m2) and type 2 diabetes (glycated hemoglobin <11% [97 mmol/mol]) were randomized (1:1:1) to once-daily finerenone, empagliflozin, or finerenone plus empagliflozin. RESULTS Among 800 participants, 182 (23%) used a GLP-1 RA at baseline. At day 180, UACR change from baseline in participants using a GLP-1 RA was −51% (95% CI −59 to −40%) with combination therapy, −34% (−48 to −18%) with finerenone, and −36% (−48 to −21%) with empagliflozin. Corresponding results in those not using a GLP-1 RA at baseline were −56% (−62 to −50%), −37% (−45 to −28%), and −33% (−41 to −23%), respectively. Hyperkalemia incidence rates with combination therapy were 9.0% and 9.5% among individuals with and without baseline GLP-1 RA use. eGFR changes were consistent among individuals with and without baseline GLP-1 RA use. Acute kidney injury was uncommon. Decreases in systolic blood pressure were observed and were more pronounced with combination therapy. CONCLUSIONS In CONFIDENCE, simultaneous initiation with finerenone and an SGLT2 inhibitor was effective and well tolerated compared with monotherapy, irrespective of background use of a GLP-1 RA.
{"title":"Impact of Baseline GLP-1 Receptor Agonist Use on Albuminuria Reduction and Safety With Simultaneous Initiation of Finerenone and Empagliflozin in Type 2 Diabetes and Chronic Kidney Disease (CONFIDENCE Trial)","authors":"Rajiv Agarwal, Jennifer B. Green, Hiddo J.L. Heerspink, Johannes F.E. Mann, Janet B. McGill, Amy K. Mottl, Masaomi Nangaku, Julio Rosenstock, Muthiah Vaduganathan, Meike Brinker, Charlie Scott, Li Li, Na Li, Katja Rohwedder, Peter Rossing","doi":"10.2337/dc25-1673","DOIUrl":"https://doi.org/10.2337/dc25-1673","url":null,"abstract":"OBJECTIVE The CONFIDENCE trial demonstrated additive benefits of simultaneous initiation of finerenone, a nonsteroidal mineralocorticoid receptor antagonist, and a sodium–glucose cotransporter 2 (SGLT2) inhibitor compared with monotherapy in reducing the urinary albumin-to-creatinine ratio (UACR). This prespecified analysis evaluated whether safety and efficacy of combination therapy varies by baseline glucagon-like peptide 1 receptor agonist (GLP-1 RA) use. RESEARCH DESIGN AND METHODS Adults with chronic kidney disease (UACR ≥100 to &lt;5,000 mg/g; estimated glomerular filtration rate [eGFR] 30–90 mL/min/1.73 m2) and type 2 diabetes (glycated hemoglobin &lt;11% [97 mmol/mol]) were randomized (1:1:1) to once-daily finerenone, empagliflozin, or finerenone plus empagliflozin. RESULTS Among 800 participants, 182 (23%) used a GLP-1 RA at baseline. At day 180, UACR change from baseline in participants using a GLP-1 RA was −51% (95% CI −59 to −40%) with combination therapy, −34% (−48 to −18%) with finerenone, and −36% (−48 to −21%) with empagliflozin. Corresponding results in those not using a GLP-1 RA at baseline were −56% (−62 to −50%), −37% (−45 to −28%), and −33% (−41 to −23%), respectively. Hyperkalemia incidence rates with combination therapy were 9.0% and 9.5% among individuals with and without baseline GLP-1 RA use. eGFR changes were consistent among individuals with and without baseline GLP-1 RA use. Acute kidney injury was uncommon. Decreases in systolic blood pressure were observed and were more pronounced with combination therapy. CONCLUSIONS In CONFIDENCE, simultaneous initiation with finerenone and an SGLT2 inhibitor was effective and well tolerated compared with monotherapy, irrespective of background use of a GLP-1 RA.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"73 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145084281","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}
Ben Nash, Loren Sher, Steven James, Ziad Nehme, Jason Talevski, Zoe Schofield, David O’Neal, Leonid Churilov, Glen Noonan, Renza Scibilia, Rodney Kwok, Elif I. Ekinci
OBJECTIVE New approaches to diabetes care are needed to better identify and manage diabetes emergencies outside of hospitals. RESEARCH DESIGN AND METHODS A descriptive analysis of routinely collected data was conducted using data from the Victorian Virtual Emergency Department (VVED) Diabetes, a telehealth service that provides emergency care, including ketone testing by ambulance personnel, for patients across Victoria, Australia, experiencing non–life-threatening diabetes-related emergencies. RESULTS Between July and December 2024, VVED Diabetes managed 868 diabetes-related emergencies, with 82.5% treated in the community, avoiding a physical emergency department visit. Referrals came from various sources, including Ambulance Victoria (26%), aged care facilities (29%), and self-registrations (20%). Hyperglycemia accounted for 46% of presentations. No clinical adverse events were reported, and patients gave positive feedback in a postdischarge survey. CONCLUSIONS VVED Diabetes delivers safe, timely, and high-quality treatment for individuals with diabetes who are acutely unwell, while ensuring the efficient use of limited hospital resources.
{"title":"Reimagining Acute Diabetes Care: Insights From the Victorian Virtual Emergency Department","authors":"Ben Nash, Loren Sher, Steven James, Ziad Nehme, Jason Talevski, Zoe Schofield, David O’Neal, Leonid Churilov, Glen Noonan, Renza Scibilia, Rodney Kwok, Elif I. Ekinci","doi":"10.2337/dc25-0852","DOIUrl":"https://doi.org/10.2337/dc25-0852","url":null,"abstract":"OBJECTIVE New approaches to diabetes care are needed to better identify and manage diabetes emergencies outside of hospitals. RESEARCH DESIGN AND METHODS A descriptive analysis of routinely collected data was conducted using data from the Victorian Virtual Emergency Department (VVED) Diabetes, a telehealth service that provides emergency care, including ketone testing by ambulance personnel, for patients across Victoria, Australia, experiencing non–life-threatening diabetes-related emergencies. RESULTS Between July and December 2024, VVED Diabetes managed 868 diabetes-related emergencies, with 82.5% treated in the community, avoiding a physical emergency department visit. Referrals came from various sources, including Ambulance Victoria (26%), aged care facilities (29%), and self-registrations (20%). Hyperglycemia accounted for 46% of presentations. No clinical adverse events were reported, and patients gave positive feedback in a postdischarge survey. CONCLUSIONS VVED Diabetes delivers safe, timely, and high-quality treatment for individuals with diabetes who are acutely unwell, while ensuring the efficient use of limited hospital resources.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"38 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145017245","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}
Anika Bilal, Fanchao Yi, Keri Whitaker, Zahra A. Khan, Richard E. Pratley, Anna Casu
OBJECTIVE Although continuous glucose monitoring (CGM) reduces hypoglycemia and may improve impaired awareness of hypoglycemia (IAH), its effectiveness in older adults at high risk remains unknown. RESEARCH DESIGN AND METHODS This post hoc analysis of the WISDM study focuses on CGM use over 52 weeks. IAH was assessed using the Clarke original score (Clarke-full) and its subscales, Hypoglycemia Awareness Factor (HAF) and Severe Hypoglycemia Experienced Factors (SHEF), at baseline, 26 weeks, and 52 weeks. RESULTS After 26 (n = 184) and 52 weeks (n = 94) of CGM use, Clarke-SHEF decreased significantly (P = 0.02 and P < 0.0001, respectively), whereas Clarke-full and Clarke-HAF remained unchanged. After 52 weeks, Clarke-full but not Clarke-HAF improved in the IAH subgroup, highlighting the importance of selecting the appropriate scoring method for IAH. CONCLUSIONS In older adults with type 1 diabetes, CGM improves hypoglycemia; however, its role in improving IAH is variable, depending on the scoring method. This study highlights the limitations of the Clarke score.
{"title":"Effects of Continuous Glucose Monitoring on Impaired Awareness of Hypoglycemia in Older Adults With Type 1 Diabetes: A Post Hoc Analysis of the WISDM Study","authors":"Anika Bilal, Fanchao Yi, Keri Whitaker, Zahra A. Khan, Richard E. Pratley, Anna Casu","doi":"10.2337/dc25-0971","DOIUrl":"https://doi.org/10.2337/dc25-0971","url":null,"abstract":"OBJECTIVE Although continuous glucose monitoring (CGM) reduces hypoglycemia and may improve impaired awareness of hypoglycemia (IAH), its effectiveness in older adults at high risk remains unknown. RESEARCH DESIGN AND METHODS This post hoc analysis of the WISDM study focuses on CGM use over 52 weeks. IAH was assessed using the Clarke original score (Clarke-full) and its subscales, Hypoglycemia Awareness Factor (HAF) and Severe Hypoglycemia Experienced Factors (SHEF), at baseline, 26 weeks, and 52 weeks. RESULTS After 26 (n = 184) and 52 weeks (n = 94) of CGM use, Clarke-SHEF decreased significantly (P = 0.02 and P &lt; 0.0001, respectively), whereas Clarke-full and Clarke-HAF remained unchanged. After 52 weeks, Clarke-full but not Clarke-HAF improved in the IAH subgroup, highlighting the importance of selecting the appropriate scoring method for IAH. CONCLUSIONS In older adults with type 1 diabetes, CGM improves hypoglycemia; however, its role in improving IAH is variable, depending on the scoring method. This study highlights the limitations of the Clarke score.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"4 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144987414","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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