Sissel Banner Lundemose, Ajenthen Gayathri Ranjan, Ole Nørgaard, Tommi Suvitaival, Kirsten Nørgaard
OBJECTIVE People with type 1 diabetes (T1D) struggle to manage exercise because of hypoglycemia risk. RESEARCH DESIGN AND METHODS This systematic review and meta-analysis evaluated low-dose glucagon's efficacy for preventing and treating exercise-induced hypoglycemia in T1D. Medline, Embase, and Cochrane CENTRAL were searched for randomized controlled trials and crossover studies until September 2024. The analysis included T1D adolescents and adults treated with low-dose glucagon versus nonglucagon treatments. Studies with glucagon-like peptides, noninsulin combinations, or uncontrolled exercise settings were excluded. Two authors extracted the data. The methodological quality was assessed with the Risk of Bias-2 tool and Grading of Recommendations Assessment, Development and Evaluations framework. Risk of Bias 2 informed a sensitivity analysis. The meta-analysis employed a random effects model to estimate the pooled treatment effects on hypoglycemia and time below range (TBR) (glucose <3.9 mmol/L), as well as secondary outcomes and adverse effects. RESULTS Of 6,792 records, 12 studies involving 248 individuals (mean age: 36 ± 10.5 years) met inclusion criteria. The meta-analysis showed significant reductions in hypoglycemia risk (risk ratio 0.54; 95% CI 0.35, 0.84) and TBR (−3.91 percentage points; 95% CI −6.27, 1.54) with low-dose glucagon. Sensitivity analysis yielded a slightly more confident effect size for hypoglycemia and TBR. However, overall adverse events increased with low-dose glucagon (risk ratio 2.75; 95% CI 1.07, 7.08). The included studies were few and heterogeneous, which may have influenced the overall outcomes. CONCLUSIONS Low-dose glucagon reduces exercise-induced hypoglycemia and TBR in T1D individuals. Future research should optimize glucagon dosage and timing for various exercise types and durations to confirm real-world effectiveness.
1型糖尿病（T1D）患者由于低血糖风险而难以控制运动。研究设计和方法本系统综述和荟萃分析评价了低剂量胰高血糖素预防和治疗T1D运动性低血糖的疗效。Medline、Embase和Cochrane CENTRAL检索了截至2024年9月的随机对照试验和交叉研究。该分析包括接受低剂量胰高血糖素与非胰高血糖素治疗的T1D青少年和成人。胰高血糖素样肽、非胰岛素组合或不受控制的运动设置的研究被排除在外。两位作者提取了这些数据。采用偏倚风险-2工具和建议分级评估、发展和评估框架对方法学质量进行评估。偏倚风险为2，进行敏感性分析。meta分析采用随机效应模型估计低血糖和低于范围时间（TBR）（葡萄糖&；lt;3.9 mmol/L）的综合治疗效果，以及次要结局和不良反应。结果在6792份记录中，12项研究涉及248名个体（平均年龄：36±10.5岁）符合纳入标准。荟萃分析显示，低剂量胰高血糖素显著降低了低血糖风险（风险比0.54;95% CI 0.35, 0.84）和TBR（- 3.91个百分点；95% CI - 6.27, 1.54）。敏感性分析对低血糖和TBR产生了更有信心的效应值。然而，低剂量胰高血糖素组总体不良事件增加（风险比2.75;95% CI 1.07, 7.08）。纳入的研究较少且异质性，这可能影响了总体结果。结论：低剂量胰高血糖素可降低T1D患者运动性低血糖和TBR。未来的研究应该优化各种运动类型和持续时间的胰高血糖素剂量和时间，以确认实际效果。
{"title":"Low-Dose Glucagon to Prevent and Treat Exercise-Associated Hypoglycemia in Individuals With Type 1 Diabetes: A Systematic Review and Meta-analysis","authors":"Sissel Banner Lundemose, Ajenthen Gayathri Ranjan, Ole Nørgaard, Tommi Suvitaival, Kirsten Nørgaard","doi":"10.2337/dc25-0702","DOIUrl":"https://doi.org/10.2337/dc25-0702","url":null,"abstract":"OBJECTIVE People with type 1 diabetes (T1D) struggle to manage exercise because of hypoglycemia risk. RESEARCH DESIGN AND METHODS This systematic review and meta-analysis evaluated low-dose glucagon's efficacy for preventing and treating exercise-induced hypoglycemia in T1D. Medline, Embase, and Cochrane CENTRAL were searched for randomized controlled trials and crossover studies until September 2024. The analysis included T1D adolescents and adults treated with low-dose glucagon versus nonglucagon treatments. Studies with glucagon-like peptides, noninsulin combinations, or uncontrolled exercise settings were excluded. Two authors extracted the data. The methodological quality was assessed with the Risk of Bias-2 tool and Grading of Recommendations Assessment, Development and Evaluations framework. Risk of Bias 2 informed a sensitivity analysis. The meta-analysis employed a random effects model to estimate the pooled treatment effects on hypoglycemia and time below range (TBR) (glucose &lt;3.9 mmol/L), as well as secondary outcomes and adverse effects. RESULTS Of 6,792 records, 12 studies involving 248 individuals (mean age: 36 ± 10.5 years) met inclusion criteria. The meta-analysis showed significant reductions in hypoglycemia risk (risk ratio 0.54; 95% CI 0.35, 0.84) and TBR (−3.91 percentage points; 95% CI −6.27, 1.54) with low-dose glucagon. Sensitivity analysis yielded a slightly more confident effect size for hypoglycemia and TBR. However, overall adverse events increased with low-dose glucagon (risk ratio 2.75; 95% CI 1.07, 7.08). The included studies were few and heterogeneous, which may have influenced the overall outcomes. CONCLUSIONS Low-dose glucagon reduces exercise-induced hypoglycemia and TBR in T1D individuals. Future research should optimize glucagon dosage and timing for various exercise types and durations to confirm real-world effectiveness.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"46 1","pages":"1637-1645"},"PeriodicalIF":16.2,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144901568","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}
Christine Ljungberg, Mette Nørgaard, Christina Vandenbroucke-Grauls, Jakob Kristian Jakobsen, Morten Haaning Charles, Anton Pottegård, Michael Dalager-Pedersen, Henrik Toft Sørensen, Reimar Wernich Thomsen
OBJECTIVE Sodium-glucose cotransporter 2 inhibitors (SGLT2i) induce glucosuria, potentially leading to infection and inflammation in the preputial microenvironment, subsequently increasing the risk of phimosis. We aimed to investigate the risks of phimosis in males with type 2 diabetes initiating SGLT2i or glucagon-like peptide-1 receptor agonists (GLP-1RA). RESEARCH DESIGN AND METHODS In this population-based active-comparator new-user cohort study emulating a target trial, we included all adult male metformin users in Denmark initiating SGLT2i or GLP-1RA between 2016 and 2021. We used inverse probability of treatment weighting to balance the distribution of potential confounders. We estimated weighted intention-to-treat risk and risk ratios of phimosis identified from population-based medical databases. RESULTS In this study, we included 32,486 SGLT2i initiators and 14,793 GLP-1RA initiators with a median follow-up of 4 years (maximum 8 years). The risk of phimosis was elevated among SGLT2i users. The 1-year risk of phimosis was 0.9% among new SGLT2i users and 0.5% among new GLP-1RA users, corresponding to a 1-year risk ratio of 1.88 (95% CI, 1.43 to 2.47). During 8 years of follow-up, the risk of phimosis accumulated up to 4.8% in SGLT2i users and 3.6% in GLP-1RA users, with an 8-year risk ratio of 1.36 (95% CI, 1.14 to 1.61). CONCLUSIONS SGLT2i use was associated with a nearly twofold increased phimosis risk 1 year after treatment initiation in men with type 2 diabetes, compared with GLP-1RA use. Over 8 years of follow-up, the risk remained elevated, indicating a persistently higher risk associated with SGLT2i use.
{"title":"Risk of Phimosis Associated With SGLT2i Versus GLP-1RA: A Danish Cohort Study","authors":"Christine Ljungberg, Mette Nørgaard, Christina Vandenbroucke-Grauls, Jakob Kristian Jakobsen, Morten Haaning Charles, Anton Pottegård, Michael Dalager-Pedersen, Henrik Toft Sørensen, Reimar Wernich Thomsen","doi":"10.2337/dc25-0693","DOIUrl":"https://doi.org/10.2337/dc25-0693","url":null,"abstract":"OBJECTIVE Sodium-glucose cotransporter 2 inhibitors (SGLT2i) induce glucosuria, potentially leading to infection and inflammation in the preputial microenvironment, subsequently increasing the risk of phimosis. We aimed to investigate the risks of phimosis in males with type 2 diabetes initiating SGLT2i or glucagon-like peptide-1 receptor agonists (GLP-1RA). RESEARCH DESIGN AND METHODS In this population-based active-comparator new-user cohort study emulating a target trial, we included all adult male metformin users in Denmark initiating SGLT2i or GLP-1RA between 2016 and 2021. We used inverse probability of treatment weighting to balance the distribution of potential confounders. We estimated weighted intention-to-treat risk and risk ratios of phimosis identified from population-based medical databases. RESULTS In this study, we included 32,486 SGLT2i initiators and 14,793 GLP-1RA initiators with a median follow-up of 4 years (maximum 8 years). The risk of phimosis was elevated among SGLT2i users. The 1-year risk of phimosis was 0.9% among new SGLT2i users and 0.5% among new GLP-1RA users, corresponding to a 1-year risk ratio of 1.88 (95% CI, 1.43 to 2.47). During 8 years of follow-up, the risk of phimosis accumulated up to 4.8% in SGLT2i users and 3.6% in GLP-1RA users, with an 8-year risk ratio of 1.36 (95% CI, 1.14 to 1.61). CONCLUSIONS SGLT2i use was associated with a nearly twofold increased phimosis risk 1 year after treatment initiation in men with type 2 diabetes, compared with GLP-1RA use. Over 8 years of follow-up, the risk remained elevated, indicating a persistently higher risk associated with SGLT2i use.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"19 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144747070","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}
Yilin Yoshida, Ngoc Quynh Nguyen, Eun Hye Moon, Casey Rebholz, Hicham Skali, Victoria Arthur, Justin B. Echouffo-Tcheugui, Christie Ballantyne, Elizabeth Selvin, Amil Shah, Robert Kaplan, Carlos J. Rodriguez, Qibin Qi, Susan Cheng, Bing Yu
OBJECTIVE Hyperglycemic states (prediabetes and diabetes) are associated with heart failure (HF) risk. We aimed to identify distinct metabolites for subclinical cardiac dysfunction, a precursor of HF, in hyperglycemic or euglycemic individuals. RESEARCH DESIGN AND METHODS We conducted cross-sectional and prospective analyses of 2,492 HF-free participants from the Atherosclerosis Risk in Communities (ARIC) study visit 5, 2011–2013. A total of 1,297 participants were hyperglycemic (assessed on the basis of hemoglobin A1c >5.7%, fasting glucose >100 mg/dL, use of diabetes medication, or diagnosis), and 1,195 were euglycemic. We used logistic regression for analysis of association between 790 metabolites and cardiac dysfunction, defined according to echocardiographic abnormalities (left ventricular hypertrophy, systolic or diastolic dysfunction) or elevated NT-proBNP or troponin T, in two glycemic groups separately. We used Cox regression for prospective association between cardiac dysfunction–related metabolites identified in the prior step and HF risk, adjusting for clinical risk factors. Analyses were replicated in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) (n = 5,167). RESULTS Microvascular disease–related metabolites (e.g., pseudouridine, N6-carbamoylthreonyladenosine, N6-acetyllysine, N2,N5-diacetylornithine) were associated with cardiac dysfunction in hyperglycemic individuals. Carbohydrate and cofactor-derived metabolites (e.g., gulonate, erythrocyte) were associated with cardiac dysfunction in euglycemic individuals. These cardiac dysfunction–related metabolites were prospectively associated with HF risk in the two glycemic groups (follow-up 7.5 years, 137 and 94 HF cases, per-SD increase hazards ratios range 1–1.9 and 1.1–2.9), respectively. HCHS/SOL results were consistent with those from ARIC. CONCLUSIONS Metabolites known for microvascular complications were associated with cardiac dysfunction in hyperglycemic individuals but not among their euglycemic counterparts, supporting the premise that microvascular dysfunction contributes to HF pathogenesis in diabetes.
{"title":"A Metabolomics Study of Cardiac Dysfunction in Hyperglycemia—Findings From the Atherosclerosis Risk in Communities (ARIC) Study and the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)","authors":"Yilin Yoshida, Ngoc Quynh Nguyen, Eun Hye Moon, Casey Rebholz, Hicham Skali, Victoria Arthur, Justin B. Echouffo-Tcheugui, Christie Ballantyne, Elizabeth Selvin, Amil Shah, Robert Kaplan, Carlos J. Rodriguez, Qibin Qi, Susan Cheng, Bing Yu","doi":"10.2337/dc25-0730","DOIUrl":"https://doi.org/10.2337/dc25-0730","url":null,"abstract":"OBJECTIVE Hyperglycemic states (prediabetes and diabetes) are associated with heart failure (HF) risk. We aimed to identify distinct metabolites for subclinical cardiac dysfunction, a precursor of HF, in hyperglycemic or euglycemic individuals. RESEARCH DESIGN AND METHODS We conducted cross-sectional and prospective analyses of 2,492 HF-free participants from the Atherosclerosis Risk in Communities (ARIC) study visit 5, 2011–2013. A total of 1,297 participants were hyperglycemic (assessed on the basis of hemoglobin A1c &gt;5.7%, fasting glucose &gt;100 mg/dL, use of diabetes medication, or diagnosis), and 1,195 were euglycemic. We used logistic regression for analysis of association between 790 metabolites and cardiac dysfunction, defined according to echocardiographic abnormalities (left ventricular hypertrophy, systolic or diastolic dysfunction) or elevated NT-proBNP or troponin T, in two glycemic groups separately. We used Cox regression for prospective association between cardiac dysfunction–related metabolites identified in the prior step and HF risk, adjusting for clinical risk factors. Analyses were replicated in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) (n = 5,167). RESULTS Microvascular disease–related metabolites (e.g., pseudouridine, N6-carbamoylthreonyladenosine, N6-acetyllysine, N2,N5-diacetylornithine) were associated with cardiac dysfunction in hyperglycemic individuals. Carbohydrate and cofactor-derived metabolites (e.g., gulonate, erythrocyte) were associated with cardiac dysfunction in euglycemic individuals. These cardiac dysfunction–related metabolites were prospectively associated with HF risk in the two glycemic groups (follow-up 7.5 years, 137 and 94 HF cases, per-SD increase hazards ratios range 1–1.9 and 1.1–2.9), respectively. HCHS/SOL results were consistent with those from ARIC. CONCLUSIONS Metabolites known for microvascular complications were associated with cardiac dysfunction in hyperglycemic individuals but not among their euglycemic counterparts, supporting the premise that microvascular dysfunction contributes to HF pathogenesis in diabetes.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"50 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144737176","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}
Lauren A. Vanderlinden, Ellen Wong, Randi K. Johnson, Patrick Carry, Fran Dong, Katerina Kechris, Marian Rewers, Jill M. Norris
OBJECTIVE Multiple studies have reported an inverse association between self-reported smoking during pregnancy and offspring type 1 diabetes (T1D) risk. We investigated the association between DNA methylation (DNAm) smoke exposure scores, parental self-reported smoking, and islet autoimmunity (IA) and T1D risk in children at high risk of T1D. RESEARCH DESIGN AND METHODS We used longitudinal data from the Diabetes Autoimmunity Study in the Young cohort, including 205 IA case and 206 control participants (87 and 88 were T1D case and control participants, respectively), matched by age, race/ethnicity, and sample availability. DNAm profiles were obtained from cord or peripheral blood using the Infinium Human Methylation 450K or EPIC BeadChip. Three published DNAm smoking scores were calculated at every time point. To estimate in utero smoke exposure, participant-specific intercepts were derived from mixed-effects models of longitudinal DNAm scores. These intercepts strongly correlated with cord blood scores (r = 0.85–0.95; n = 179), indicating their utility as proxies for in utero smoke exposure. Associations with IA/T1D were evaluated using logistic regression, adjusting for HLA-DR3/4, first-degree relative status, and sex. RESULTS Multivariable models showed both maternally reported smoking during pregnancy and higher DNAm smoking scores to be associated with lower risk of IA and T1D. Maternal smoking showed a strong inverse association with IA (odds ratio [OR] 0.24; 95% CI 0.10–0.54). Rauschert and McCartney DNAm scores showed consistent inverse associations with both outcomes (OR 0.65–0.83 for SD increase). CONCLUSIONS Our study supports existing literature indicating in utero smoke exposure is associated with reduced IA and T1D risk. Further research is essential to uncover the underlying mechanisms.
目的：多项研究报道了妊娠期间自我报告吸烟与后代1型糖尿病（T1D）风险之间的负相关关系。我们调查了DNA甲基化（DNAm）烟雾暴露评分、父母自我报告吸烟、胰岛自身免疫（IA）和T1D高风险儿童T1D风险之间的关系。研究设计和方法我们使用了来自年轻队列糖尿病自身免疫研究的纵向数据，包括205例IA患者和206例对照受试者（分别为87例和88例T1D患者和对照受试者），根据年龄、种族/民族和样本可用性进行匹配。使用Infinium Human Methylation 450K或EPIC BeadChip从脐带或外周血中获得dna谱。在每个时间点计算三个公布的DNAm吸烟评分。为了估计子宫内的烟雾暴露，参与者特定的拦截来自纵向DNAm评分的混合效应模型。这些截距与脐带血评分密切相关(r = 0.85-0.95；N = 179)，表明它们作为子宫内烟雾暴露的代理的效用。在调整HLA-DR3/4、一级相对地位和性别后，采用logistic回归评估IA/T1D的相关性。结果多变量模型显示，母亲在怀孕期间报告吸烟和较高的DNAm吸烟评分与较低的IA和T1D风险相关。母亲吸烟与IA呈强烈的负相关(优势比[OR] 0.24；95% ci 0.10-0.54)。Rauschert和McCartney DNAm评分与两种结果呈一致的负相关（SD增加的OR为0.65-0.83）。结论：我们的研究支持现有文献，表明子宫内吸烟暴露与IA和T1D风险降低相关。进一步的研究对于揭示潜在的机制至关重要。
{"title":"DNA Methylation Smoking Scores and Risk of Islet Autoimmunity and Type 1 Diabetes","authors":"Lauren A. Vanderlinden, Ellen Wong, Randi K. Johnson, Patrick Carry, Fran Dong, Katerina Kechris, Marian Rewers, Jill M. Norris","doi":"10.2337/dc25-0330","DOIUrl":"https://doi.org/10.2337/dc25-0330","url":null,"abstract":"OBJECTIVE Multiple studies have reported an inverse association between self-reported smoking during pregnancy and offspring type 1 diabetes (T1D) risk. We investigated the association between DNA methylation (DNAm) smoke exposure scores, parental self-reported smoking, and islet autoimmunity (IA) and T1D risk in children at high risk of T1D. RESEARCH DESIGN AND METHODS We used longitudinal data from the Diabetes Autoimmunity Study in the Young cohort, including 205 IA case and 206 control participants (87 and 88 were T1D case and control participants, respectively), matched by age, race/ethnicity, and sample availability. DNAm profiles were obtained from cord or peripheral blood using the Infinium Human Methylation 450K or EPIC BeadChip. Three published DNAm smoking scores were calculated at every time point. To estimate in utero smoke exposure, participant-specific intercepts were derived from mixed-effects models of longitudinal DNAm scores. These intercepts strongly correlated with cord blood scores (r = 0.85–0.95; n = 179), indicating their utility as proxies for in utero smoke exposure. Associations with IA/T1D were evaluated using logistic regression, adjusting for HLA-DR3/4, first-degree relative status, and sex. RESULTS Multivariable models showed both maternally reported smoking during pregnancy and higher DNAm smoking scores to be associated with lower risk of IA and T1D. Maternal smoking showed a strong inverse association with IA (odds ratio [OR] 0.24; 95% CI 0.10–0.54). Rauschert and McCartney DNAm scores showed consistent inverse associations with both outcomes (OR 0.65–0.83 for SD increase). CONCLUSIONS Our study supports existing literature indicating in utero smoke exposure is associated with reduced IA and T1D risk. Further research is essential to uncover the underlying mechanisms.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"27 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144712321","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}
Erin L. Templeman, Lauric A. Ferrat, Nicholas Thomas, Cate Speake, Diane K. Wherrett, Jennifer Sherr, John M. Wentworth, Maria J. Redondo, Hemang M. Parik, Jamie L. Felton, Carmella Evans-Molina, Jay Sosenko, Lu You, Richard A. Oram, Emily K. Sims
OBJECTIVE More than half of incident type 1 diabetes (T1D) occurs in adults, yet research on disease progression predominantly focuses on at-risk children. We compared autoantibody screening outcomes and T1D progression in adults versus children. RESEARCH DESIGN AND METHODS We studied 135,914 children (aged <18 years) and 99,795 adult relatives of individuals with T1D screened in the TrialNet Pathway to Prevention study. In autoantibody positive participants, we compared progression rates, associations with risk factors, and performance of metabolic risk scores. RESULTS Adults were more likely than children to screen positive for a single autoantibody (4.0% vs. 2.6%) but less likely for multiple autoantibodies (0.83% vs. 2.8%; P < 0.001). Progression to stage 3 disease was lower in adults with single autoantibody positivity or stage 1 T1D than in children (5-year risks: single autoantibody, adults 8.2% vs. children 22%, P < 0.001; stage 1, adults 17% vs. children 47%, P < 0.001). However, adults with stage 2 T1D at initial staging oral glucose tolerance test had comparable 5-year progression risks to children (78% for both groups). A higher proportion of adults progressing to clinical diabetes were single autoantibody positive (40% vs. 15%; P < 0.0001); these individuals commonly had single glutamic acid decarboxylase positivity and had lower type 1 but higher type 2 genetic risk scores compared with multiple autoantibody positive adults. HbA1c and established risk indices more effectively identified progressors in adults compared with children. CONCLUSIONS Autoantibody positive adult relatives have distinct autoantibody trajectories and progression risks compared with children, suggesting the need for tailored monitoring and intervention strategies.
超过一半的1型糖尿病（T1D）发生在成人中，但疾病进展的研究主要集中在高危儿童身上。我们比较了成人和儿童的自身抗体筛查结果和T1D进展。研究设计和方法我们研究了在TrialNet预防途径研究中筛选的135,914名儿童（18岁）和99,795名T1D患者的成年亲属。在自身抗体阳性的参与者中，我们比较了进展率、与危险因素的关联以及代谢风险评分的表现。结果：成人比儿童更有可能筛查出单一自身抗体阳性（4.0%比2.6%），但筛查出多种自身抗体阳性的可能性较低(0.83%比2.8%；P, lt;0.001)。成人单一自身抗体阳性或1期T1D患者进展至3期疾病的风险低于儿童(5年风险：成人单一自身抗体8.2% vs儿童22%，P <；0.001;第一阶段，成人17%，儿童47%，P <；0.001)。然而，在初始阶段口服糖耐量试验中，成人2期T1D患者的5年进展风险与儿童相当（两组均为78%）。单个自身抗体阳性的成年人发展为临床糖尿病的比例更高(40% vs 15%；P, lt;0.0001);这些个体通常具有单一谷氨酸脱羧酶阳性，与多种自身抗体阳性的成年人相比，具有较低的1型遗传风险评分，但较高的2型遗传风险评分。与儿童相比，HbA1c和已建立的风险指标更有效地识别成人的进展。结论与儿童相比，自身抗体阳性的成年亲属具有不同的自身抗体轨迹和进展风险，提示需要定制监测和干预策略。
{"title":"Contrasting Adult and Pediatric Populations in a Cohort of At-Risk Relatives in The T1D TrialNet Pathway to Prevention Study","authors":"Erin L. Templeman, Lauric A. Ferrat, Nicholas Thomas, Cate Speake, Diane K. Wherrett, Jennifer Sherr, John M. Wentworth, Maria J. Redondo, Hemang M. Parik, Jamie L. Felton, Carmella Evans-Molina, Jay Sosenko, Lu You, Richard A. Oram, Emily K. Sims","doi":"10.2337/dc25-0192","DOIUrl":"https://doi.org/10.2337/dc25-0192","url":null,"abstract":"OBJECTIVE More than half of incident type 1 diabetes (T1D) occurs in adults, yet research on disease progression predominantly focuses on at-risk children. We compared autoantibody screening outcomes and T1D progression in adults versus children. RESEARCH DESIGN AND METHODS We studied 135,914 children (aged &lt;18 years) and 99,795 adult relatives of individuals with T1D screened in the TrialNet Pathway to Prevention study. In autoantibody positive participants, we compared progression rates, associations with risk factors, and performance of metabolic risk scores. RESULTS Adults were more likely than children to screen positive for a single autoantibody (4.0% vs. 2.6%) but less likely for multiple autoantibodies (0.83% vs. 2.8%; P &lt; 0.001). Progression to stage 3 disease was lower in adults with single autoantibody positivity or stage 1 T1D than in children (5-year risks: single autoantibody, adults 8.2% vs. children 22%, P &lt; 0.001; stage 1, adults 17% vs. children 47%, P &lt; 0.001). However, adults with stage 2 T1D at initial staging oral glucose tolerance test had comparable 5-year progression risks to children (78% for both groups). A higher proportion of adults progressing to clinical diabetes were single autoantibody positive (40% vs. 15%; P &lt; 0.0001); these individuals commonly had single glutamic acid decarboxylase positivity and had lower type 1 but higher type 2 genetic risk scores compared with multiple autoantibody positive adults. HbA1c and established risk indices more effectively identified progressors in adults compared with children. CONCLUSIONS Autoantibody positive adult relatives have distinct autoantibody trajectories and progression risks compared with children, suggesting the need for tailored monitoring and intervention strategies.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"11 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684725","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}
Andrea Mari, Adam Stefanski, Daniel H. van Raalte, Xiaosu Ma, Elizabeth S. LaBell, Ludi Fan, Clare J. Lee, Melissa K. Thomas, Mathijs C. Bunck, Ele Ferrannini
OBJECTIVE We assessed insulin sensitivity and β-cell function in adults with obesity/overweight, without diabetes, treated with tirzepatide for 72 weeks. RESEARCH DESIGN AND METHODS This post hoc analysis from the Study of Tirzepatide (LY3298176) in Participants With Obesity or Overweight (SURMOUNT-1) trial investigated tirzepatide versus placebo in 2,539 participants with BMI ≥27 kg/m2 and either prediabetes or normoglycemia at baseline. Model-derived parameters of β-cell function and insulin sensitivity were assessed from oral glucose tolerance tests. RESULTS At week 72, tirzepatide treatment was associated with body weight reduction and improvements in insulin sensitivity and β-cell function measures overall and in participants with prediabetes or normoglycemia. In multivariate regression models, improvements in insulin sensitivity were associated mostly with weight reduction and partly with tirzepatide treatment, whereas enhancement in β-cell function was mostly associated with tirzepatide treatment. CONCLUSIONS In adults with obesity/overweight without type 2 diabetes, tirzepatide treatment was associated with improved β-cell function and insulin sensitivity, partly independent of weight reduction.
{"title":"Tirzepatide Treatment and Associated Changes in β-Cell Function and Insulin Sensitivity in People With Obesity or Overweight With Prediabetes or Normoglycemia: A Post Hoc Analysis From the SURMOUNT-1 Trial","authors":"Andrea Mari, Adam Stefanski, Daniel H. van Raalte, Xiaosu Ma, Elizabeth S. LaBell, Ludi Fan, Clare J. Lee, Melissa K. Thomas, Mathijs C. Bunck, Ele Ferrannini","doi":"10.2337/dc25-0763","DOIUrl":"https://doi.org/10.2337/dc25-0763","url":null,"abstract":"OBJECTIVE We assessed insulin sensitivity and β-cell function in adults with obesity/overweight, without diabetes, treated with tirzepatide for 72 weeks. RESEARCH DESIGN AND METHODS This post hoc analysis from the Study of Tirzepatide (LY3298176) in Participants With Obesity or Overweight (SURMOUNT-1) trial investigated tirzepatide versus placebo in 2,539 participants with BMI ≥27 kg/m2 and either prediabetes or normoglycemia at baseline. Model-derived parameters of β-cell function and insulin sensitivity were assessed from oral glucose tolerance tests. RESULTS At week 72, tirzepatide treatment was associated with body weight reduction and improvements in insulin sensitivity and β-cell function measures overall and in participants with prediabetes or normoglycemia. In multivariate regression models, improvements in insulin sensitivity were associated mostly with weight reduction and partly with tirzepatide treatment, whereas enhancement in β-cell function was mostly associated with tirzepatide treatment. CONCLUSIONS In adults with obesity/overweight without type 2 diabetes, tirzepatide treatment was associated with improved β-cell function and insulin sensitivity, partly independent of weight reduction.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"52 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684732","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}
Piotr Witkowski, Anne Eaton, Sydney Porter, Maisam Abu-El-Haija, Syed A. Ahmad, Sri Prakash Mokshagundam, Martin Wijkstrom, Bashoo Naziruddin, Guru Trikudanathan, Vikesh K. Singh, Sarah J. Schwarzenberg, Timothy L. Pruett, Andrew Posselt, Jaimie D. Nathan, Katherine Morgan, Luis F. Lara, Timothy B. Gardner, Martin Freeman, Mayha Faghih, Elissa M. Downs, Srinath Chinnakotla, Appakalai N. Balamurugan, David Adams, Gregory J. Beilman, Melena D. Bellin
OBJECTIVE Total pancreatectomy with islet autotransplantation (TPIAT) may relieve pain for patients with intractable recurrent acute or chronic pancreatitis. In this first multicenter cohort study of TPIAT, we aimed to identify predictors of favorable diabetes outcomes following TPIAT to aid in surgical counseling and decision making. RESEARCH DESIGN AND METHODS We included 384 patients (mean [SD] age 29.6 [17.1] years; 61.7% female) who underwent TPIAT and were enrolled in the National Institutes of Health–sponsored multicenter Prospective Observational Study of TPIAT (POST). Outcomes were reported for insulin use, HbA1c, and islet graft function. Univariable and multivariable modeling was performed to evaluate predictors of diabetes outcomes after TPIAT. RESULTS At 1 year post-TPIAT, 83% of patients retained islet function (C-peptide >0.3 ng/mL), 20% were off insulin, and 60% had HbA1c <7%. Outcomes were most favorable in those with normoglycemia pre-TPIAT and in children. In multivariable analysis, insulin independence at 1 year was associated with pediatric age (odds ratio [OR] 2.3 [95% CI 1.3–4.3] vs. adults) and pretransplant HbA1c (OR 4.0 [1.7–9.1] per 1% decrease HbA1c). The odds of achieving a goal HbA1c <7% was associated with White race (OR 4.3 [1.7–11]) and pre-TPIAT HbA1c (OR 2.2 [1.1–4.3] per 1% decrease). Islet graft function was associated with pre-TPIAT fasting C-peptide (OR 2.18 [1.42–3.35] per 1 ng/mL increase) and baseline HbA1c (OR 1.89 [1.18–3] per 1% decrease). CONCLUSIONS Patients with normoglycemia and children more often were off insulin. In multivariable models, pre-TPIAT HbA1c was strongly predictive of insulin independence, islet function, and HbA1c <7% at 1 year.
目的全胰切除术联合胰岛自体移植（TPIAT）可以缓解难治性复发性急性或慢性胰腺炎患者的疼痛。在这首个TPIAT的多中心队列研究中，我们旨在确定TPIAT后糖尿病预后的预测因素，以帮助手术咨询和决策。研究设计和方法纳入384例患者(平均[SD]年龄29.6[17.1]岁；61.7%的女性)接受TPIAT，并被纳入美国国立卫生研究院赞助的TPIAT多中心前瞻性观察研究（POST）。报告了胰岛素使用、HbA1c和胰岛移植功能的结果。采用单变量和多变量模型来评估TPIAT后糖尿病结局的预测因素。结果：tpiat后1年，83%的患者保留了胰岛功能（c肽0.3 ng/mL）， 20%的患者胰岛素停用，60%的患者HbA1c降至7%。在tpiat前血糖正常的患者和儿童中，结果最有利。在多变量分析中，1年时胰岛素独立性与儿童年龄（比值比[OR] 2.3 [95% CI 1.3-4.3] vs成人）和移植前HbA1c（比值比[OR] 4.0 [1.7-9.1] / HbA1c每降低1%）相关。实现HbA1c降低7%目标的几率与白种人（OR为4.3[1.7-11]）和tpiat前HbA1c （OR为2.2[1.1-4.3]）有关。胰岛移植功能与tpiat前空腹c肽（每增加1 ng/mL OR 2.18[1.42-3.35]）和基线HbA1c（每降低1% OR 1.89[1.18-3]）相关。结论血糖正常的患者和儿童停用胰岛素的情况较多。在多变量模型中，tpiat前HbA1c可强烈预测胰岛素独立性、胰岛功能和1年时HbA1c [lt；7%]。
{"title":"Predictors of Diabetes Outcomes at 1 Year After Islet Autotransplantation: Data From a Multicenter Cohort Study","authors":"Piotr Witkowski, Anne Eaton, Sydney Porter, Maisam Abu-El-Haija, Syed A. Ahmad, Sri Prakash Mokshagundam, Martin Wijkstrom, Bashoo Naziruddin, Guru Trikudanathan, Vikesh K. Singh, Sarah J. Schwarzenberg, Timothy L. Pruett, Andrew Posselt, Jaimie D. Nathan, Katherine Morgan, Luis F. Lara, Timothy B. Gardner, Martin Freeman, Mayha Faghih, Elissa M. Downs, Srinath Chinnakotla, Appakalai N. Balamurugan, David Adams, Gregory J. Beilman, Melena D. Bellin","doi":"10.2337/dc25-0620","DOIUrl":"https://doi.org/10.2337/dc25-0620","url":null,"abstract":"OBJECTIVE Total pancreatectomy with islet autotransplantation (TPIAT) may relieve pain for patients with intractable recurrent acute or chronic pancreatitis. In this first multicenter cohort study of TPIAT, we aimed to identify predictors of favorable diabetes outcomes following TPIAT to aid in surgical counseling and decision making. RESEARCH DESIGN AND METHODS We included 384 patients (mean [SD] age 29.6 [17.1] years; 61.7% female) who underwent TPIAT and were enrolled in the National Institutes of Health–sponsored multicenter Prospective Observational Study of TPIAT (POST). Outcomes were reported for insulin use, HbA1c, and islet graft function. Univariable and multivariable modeling was performed to evaluate predictors of diabetes outcomes after TPIAT. RESULTS At 1 year post-TPIAT, 83% of patients retained islet function (C-peptide &gt;0.3 ng/mL), 20% were off insulin, and 60% had HbA1c &lt;7%. Outcomes were most favorable in those with normoglycemia pre-TPIAT and in children. In multivariable analysis, insulin independence at 1 year was associated with pediatric age (odds ratio [OR] 2.3 [95% CI 1.3–4.3] vs. adults) and pretransplant HbA1c (OR 4.0 [1.7–9.1] per 1% decrease HbA1c). The odds of achieving a goal HbA1c &lt;7% was associated with White race (OR 4.3 [1.7–11]) and pre-TPIAT HbA1c (OR 2.2 [1.1–4.3] per 1% decrease). Islet graft function was associated with pre-TPIAT fasting C-peptide (OR 2.18 [1.42–3.35] per 1 ng/mL increase) and baseline HbA1c (OR 1.89 [1.18–3] per 1% decrease). CONCLUSIONS Patients with normoglycemia and children more often were off insulin. In multivariable models, pre-TPIAT HbA1c was strongly predictive of insulin independence, islet function, and HbA1c &lt;7% at 1 year.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"103 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144593907","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}
Curtis Triplitt, Eugenio Cersosimo, Mariam Alatrach, John Adams, Andrea Hansis-Diarte, Gozde Baskoy, Amalia Gastaldelli, Alberto Chavez-Velazquez, Ralph A. DeFronzo
OBJECTIVE To examine the effects of sodium–glucose cotransporter 2 inhibitors (SGLT2is) alone or with glucagon-like peptide 1 receptor agonists (GLP-1RAs) on β-cell function (BCF) in type 2 diabetes. The hypothesis was that an SGLT2i combined with a GLP-1RA provides superior improvement in BCF than either agent alone. RESEARCH DESIGN AND METHODS Ninety patients underwent a 180-min oral glucose tolerance test (OGTT) 1) after one drug dose (acute study) (placebo [n = 15], dapagliflozin [n = 25], exenatide [n = 25], and dapagliflozin/exenatide [n = 25]), and 2) after 1 and 4 months of therapy. Corrected Matsuda index (cMI) for urinary glucose loss, insulin secretion, and BCF indices were calculated during OGTT. RESULTS In the acute study, mean ± SEM cMI in dapagliflozin (2.29 ± 0.33), exenatide (2.03 ± 0.12), and dapagliflozin/exenatide (2.36 ± 0.14) was higher (P < 0.05) than placebo (1.63 ± 0.36). After 1 and 4 months, cMI remained similarly elevated in exenatide and increased further (P < 0.001) in dapagliflozin and dapagliflozin/exenatide. In the acute study, insulin secretion in dapagliflozin was similar to placebo but higher (P < 0.001 vs. both) in exenatide and dapagliflozin/exenatide. After 1 and 4 months in exenatide and in dapagliflozin/ exenatide, insulin secretion remained higher (P < 0.01 vs. both) than dapagliflozin. BCF index in the acute study was 0.40 ± 0.04 in placebo, 62% higher (P < 0.05) in dapagliflozin (0.65 ± 0.10), threefold higher in exenatide (1.17 ± 0.22), and fourfold higher in dapagliflozin/exenatide (1.69 ± 0.12) (all P < 0.001 vs. placebo). At 1 and 4 months, BCF rose further in dapagliflozin and exenatide but did not increase further in dapagliflozin/exenatide. CONCLUSIONS Dapagliflozin and exenatide monotherapy cause sustained improvements in BCF and insulin sensitivity. Combination therapy with dapagliflozin plus exenatide markedly augmented both BCF and insulin sensitivity above that with either agent alone.
{"title":"Changes in β-Cell Function and Insulin Sensitivity During Treatment With Dapagliflozin Alone or in Combination With Exenatide in Type 2 Diabetes","authors":"Curtis Triplitt, Eugenio Cersosimo, Mariam Alatrach, John Adams, Andrea Hansis-Diarte, Gozde Baskoy, Amalia Gastaldelli, Alberto Chavez-Velazquez, Ralph A. DeFronzo","doi":"10.2337/dc25-0490","DOIUrl":"https://doi.org/10.2337/dc25-0490","url":null,"abstract":"OBJECTIVE To examine the effects of sodium–glucose cotransporter 2 inhibitors (SGLT2is) alone or with glucagon-like peptide 1 receptor agonists (GLP-1RAs) on β-cell function (BCF) in type 2 diabetes. The hypothesis was that an SGLT2i combined with a GLP-1RA provides superior improvement in BCF than either agent alone. RESEARCH DESIGN AND METHODS Ninety patients underwent a 180-min oral glucose tolerance test (OGTT) 1) after one drug dose (acute study) (placebo [n = 15], dapagliflozin [n = 25], exenatide [n = 25], and dapagliflozin/exenatide [n = 25]), and 2) after 1 and 4 months of therapy. Corrected Matsuda index (cMI) for urinary glucose loss, insulin secretion, and BCF indices were calculated during OGTT. RESULTS In the acute study, mean ± SEM cMI in dapagliflozin (2.29 ± 0.33), exenatide (2.03 ± 0.12), and dapagliflozin/exenatide (2.36 ± 0.14) was higher (P &lt; 0.05) than placebo (1.63 ± 0.36). After 1 and 4 months, cMI remained similarly elevated in exenatide and increased further (P &lt; 0.001) in dapagliflozin and dapagliflozin/exenatide. In the acute study, insulin secretion in dapagliflozin was similar to placebo but higher (P &lt; 0.001 vs. both) in exenatide and dapagliflozin/exenatide. After 1 and 4 months in exenatide and in dapagliflozin/ exenatide, insulin secretion remained higher (P &lt; 0.01 vs. both) than dapagliflozin. BCF index in the acute study was 0.40 ± 0.04 in placebo, 62% higher (P &lt; 0.05) in dapagliflozin (0.65 ± 0.10), threefold higher in exenatide (1.17 ± 0.22), and fourfold higher in dapagliflozin/exenatide (1.69 ± 0.12) (all P &lt; 0.001 vs. placebo). At 1 and 4 months, BCF rose further in dapagliflozin and exenatide but did not increase further in dapagliflozin/exenatide. CONCLUSIONS Dapagliflozin and exenatide monotherapy cause sustained improvements in BCF and insulin sensitivity. Combination therapy with dapagliflozin plus exenatide markedly augmented both BCF and insulin sensitivity above that with either agent alone.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"687 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144586246","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}
Jaehyeong Cho, Selin Woo, Seung Ha Hwang, Soeun Kim, Hayeon Lee, Jiyoung Hwang, Jaewon Kim, Min Seo Kim, Lee Smith, Sooji Lee, Jinseok Lee, Hong-Hee Won, Sang Youl Rhee, Dong Keon Yon
OBJECTIVE To develop a multimodal model to predict chronic kidney disease (CKD) in patients with type 2 diabetes mellitus (T2DM), given the limited research on this integrative approach. RESEARCH DESIGN AND METHODS We obtained multimodal data sets from Kyung Hee University Medical Center (n = 7,028; discovery cohort) for training and internal validation and UK Biobank (n = 1,544; validation cohort) for external validation. CKD was defined based on ICD-9 and ICD-10 codes and/or estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73 m2. We ensembled various deep learning models and interpreted their predictions using explainable artificial intelligence (AI) methods, including shapley additive explanations (SHAP) and gradient-weighted class activation mapping (Grad-CAM). Subsequently, we investigated the potential association between the model probability and vascular complications. RESULTS The multimodal model, which ensembles visual geometry group 16 and deep neural network, presented high performance in predicting CKD, with area under the receiver operating characteristic curve of 0.880 (95% CI, 0.806–0.954) in the discovery cohort and 0.722 in the validation cohort. SHAP and Grad-CAM highlighted key predictors, including eGFR and optic disc, respectively. The model probability was associated with an increased risk of macrovascular complications (tertile 1 [T1]: adjusted hazard ratio, 1.42 [95% CI, 1.06–1.90]; T2: 1.59 [1.17–2.16]; T3: 1.64 [1.20–2.26]) and microvascular complications (T3: 1.30 [1.02–1.67]). CONCLUSIONS Our multimodal AI model integrates fundus images and clinical data from binational cohorts to predict the risk of new-onset CKD within 5 years and associated vascular complications in patients with T2DM.
{"title":"A Multimodal Predictive Model for Chronic Kidney Disease and Its Association With Vascular Complications in Patients With Type 2 Diabetes: Model Development and Validation Study in South Korea and the U.K.","authors":"Jaehyeong Cho, Selin Woo, Seung Ha Hwang, Soeun Kim, Hayeon Lee, Jiyoung Hwang, Jaewon Kim, Min Seo Kim, Lee Smith, Sooji Lee, Jinseok Lee, Hong-Hee Won, Sang Youl Rhee, Dong Keon Yon","doi":"10.2337/dc25-0355","DOIUrl":"https://doi.org/10.2337/dc25-0355","url":null,"abstract":"OBJECTIVE To develop a multimodal model to predict chronic kidney disease (CKD) in patients with type 2 diabetes mellitus (T2DM), given the limited research on this integrative approach. RESEARCH DESIGN AND METHODS We obtained multimodal data sets from Kyung Hee University Medical Center (n = 7,028; discovery cohort) for training and internal validation and UK Biobank (n = 1,544; validation cohort) for external validation. CKD was defined based on ICD-9 and ICD-10 codes and/or estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73 m2. We ensembled various deep learning models and interpreted their predictions using explainable artificial intelligence (AI) methods, including shapley additive explanations (SHAP) and gradient-weighted class activation mapping (Grad-CAM). Subsequently, we investigated the potential association between the model probability and vascular complications. RESULTS The multimodal model, which ensembles visual geometry group 16 and deep neural network, presented high performance in predicting CKD, with area under the receiver operating characteristic curve of 0.880 (95% CI, 0.806–0.954) in the discovery cohort and 0.722 in the validation cohort. SHAP and Grad-CAM highlighted key predictors, including eGFR and optic disc, respectively. The model probability was associated with an increased risk of macrovascular complications (tertile 1 [T1]: adjusted hazard ratio, 1.42 [95% CI, 1.06–1.90]; T2: 1.59 [1.17–2.16]; T3: 1.64 [1.20–2.26]) and microvascular complications (T3: 1.30 [1.02–1.67]). CONCLUSIONS Our multimodal AI model integrates fundus images and clinical data from binational cohorts to predict the risk of new-onset CKD within 5 years and associated vascular complications in patients with T2DM.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"49 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144533067","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}
Adrian Matias Bacong, Veronica Njuguna, Jeanne Darbinian, Luis A. Rodriguez, Erica P. Gunderson, Louise C. Greenspan, Nitya Rajeshuni, Latha Palaniappan, Joan C. Lo
OBJECTIVE To compare prediabetes prevalence among disaggregated U.S. Asian and Pacific Islander (Asian/PI) adolescents with non-Hispanic White (NHW) adolescents with overweight or obesity in a primary care population. RESEARCH DESIGN AND METHODS This retrospective, cross-sectional study used Kaiser Permanente Northern California health record data. The cohort comprised 20,540 NHW and 16,508 Asian/PI adolescents aged 10–17 years with overweight (BMI 85th to <95th percentile) or obesity (BMI ≥95th percentile) at a pediatric visit (2012–2019) and HbA1c measured within 1 year. Those with HbA1c ≥6.5%, a diabetes diagnosis, or diabetes pharmacotherapy were excluded. Prediabetes was classified as HbA1c 5.7–6.4%. Adjusted prevalence ratios (aPRs) with 95% CIs for prediabetes were examined for Filipino, Chinese, South Asian, Vietnamese, and Native Hawaiian/Pacific Islander (NHPI) compared with NHW using modified Poisson regression, adjusting for age, sex, BMI, neighborhood deprivation index, and visit year. RESULTS Asian/PI adolescents with overweight or obesity had a higher prediabetes prevalence (26.9%) than NHW adolescents (11.9%) (P < 0.001), with variation among Asian subgroups of 31.0% for South Asian, 32.0% for NHPI, 28.2% for Filipino, 25.9% for Chinese, and 18.4% for Vietnamese adolescents. In multivariable analyses, the aPRs for prediabetes (vs. NHW) were 2.80 (95% CI, 2.57–3.05) for South Asian, 2.44 (2.23–2.67) for NHPI, 2.18 (2.06–2.32) for Filipino, 2.18 (1.99–2.39) for Chinese, and 1.68 (1.38–2.04) for Vietnamese adolescents. These findings were similar by sex, and patterns were similar within overweight or obesity subgroups. CONCLUSIONS Asian/PI adolescents with overweight or obesity have considerably higher prediabetes prevalence than NHW adolescents, independent of BMI. Findings varied by ethnicity. Prediabetes screening is essential for the high-risk population of Asian/PI adolescents with overweight or obesity.
{"title":"High Prevalence of Prediabetes Among Asian and Pacific Islander Adolescents With Overweight or Obesity in a Primary Care Population","authors":"Adrian Matias Bacong, Veronica Njuguna, Jeanne Darbinian, Luis A. Rodriguez, Erica P. Gunderson, Louise C. Greenspan, Nitya Rajeshuni, Latha Palaniappan, Joan C. Lo","doi":"10.2337/dc25-0343","DOIUrl":"https://doi.org/10.2337/dc25-0343","url":null,"abstract":"OBJECTIVE To compare prediabetes prevalence among disaggregated U.S. Asian and Pacific Islander (Asian/PI) adolescents with non-Hispanic White (NHW) adolescents with overweight or obesity in a primary care population. RESEARCH DESIGN AND METHODS This retrospective, cross-sectional study used Kaiser Permanente Northern California health record data. The cohort comprised 20,540 NHW and 16,508 Asian/PI adolescents aged 10–17 years with overweight (BMI 85th to &lt;95th percentile) or obesity (BMI ≥95th percentile) at a pediatric visit (2012–2019) and HbA1c measured within 1 year. Those with HbA1c ≥6.5%, a diabetes diagnosis, or diabetes pharmacotherapy were excluded. Prediabetes was classified as HbA1c 5.7–6.4%. Adjusted prevalence ratios (aPRs) with 95% CIs for prediabetes were examined for Filipino, Chinese, South Asian, Vietnamese, and Native Hawaiian/Pacific Islander (NHPI) compared with NHW using modified Poisson regression, adjusting for age, sex, BMI, neighborhood deprivation index, and visit year. RESULTS Asian/PI adolescents with overweight or obesity had a higher prediabetes prevalence (26.9%) than NHW adolescents (11.9%) (P &lt; 0.001), with variation among Asian subgroups of 31.0% for South Asian, 32.0% for NHPI, 28.2% for Filipino, 25.9% for Chinese, and 18.4% for Vietnamese adolescents. In multivariable analyses, the aPRs for prediabetes (vs. NHW) were 2.80 (95% CI, 2.57–3.05) for South Asian, 2.44 (2.23–2.67) for NHPI, 2.18 (2.06–2.32) for Filipino, 2.18 (1.99–2.39) for Chinese, and 1.68 (1.38–2.04) for Vietnamese adolescents. These findings were similar by sex, and patterns were similar within overweight or obesity subgroups. CONCLUSIONS Asian/PI adolescents with overweight or obesity have considerably higher prediabetes prevalence than NHW adolescents, independent of BMI. Findings varied by ethnicity. Prediabetes screening is essential for the high-risk population of Asian/PI adolescents with overweight or obesity.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"635 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144520353","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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