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 >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.","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}
Lin Li, Ruyi Li, Zixin Qiu, Kai Zhu, Rui Li, Shiyu Zhao, Jiajing Che, Tianyu Guo, Kun Xu, Tingting Geng, Yunfei Liao, An Pan, Gang Liu
OBJECTIVE To identify baseline multiomic and phenotypic predictors and develop prediction models for weight and body composition loss and regain in the Low-Carbohydrate Diet and Time-Restricted Eating (LEAN-TIME) trial. RESEARCH DESIGN AND METHODS A post hoc analysis was conducted of the LEAN-TIME feeding trial using data from 88 adults with overweight/obesity completing a 12-week calorie-restricted weight-loss phase and 79 completing a 28-week weight-regain phase. Baseline dietary, metabolic, fecal metabolome, and gut microbiome data were candidate predictors of changes in weight, body fat mass (BFM), and soft lean mass (SLM). Multivariable regression and the least absolute shrinkage and selection operator model were used to identify predictors and develop weighted-sum prediction models. RESULTS Multiomic and phenotypic models significantly outperformed phenotype-only models (P < 0.05), demonstrating strong predictive performance during both phases. During weight loss, the multiomic and phenotypic model yielded R2 values of 0.49, 0.61, and 0.54 for changes in weight, BFM, and SLM, respectively, with corresponding root mean square errors (RMSEs) of 1.59, 1.41, and 0.98 kg. For binary classification of clinically meaningful weight loss (≥5%), the model achieved an area under the curve of 0.95 (sensitivity 94.12%; specificity 86.79%). During weight regain, R2 values reached 0.72, 0.73, and 0.66 for weight, BFM, and SLM (RMSEs 1.40, 1.62, and 0.73 kg), respectively. Several key baseline predictors, primarily gut microbes and fecal metabolites, such as N-acetyl-l-aspartic acid, Ruminococcus callidus, and Bifidobacterium adolescentis, were shared for weight and body composition changes during both phases. CONCLUSIONS Baseline multiomic and phenotypic data effectively predict weight and body composition loss and regain, offering insights for personalized weight management.
{"title":"Prediction of Weight Loss and Regain Based on Multiomic and Phenotypic Features: Results From a Calorie-Restricted Feeding Trial","authors":"Lin Li, Ruyi Li, Zixin Qiu, Kai Zhu, Rui Li, Shiyu Zhao, Jiajing Che, Tianyu Guo, Kun Xu, Tingting Geng, Yunfei Liao, An Pan, Gang Liu","doi":"10.2337/dc25-0728","DOIUrl":"https://doi.org/10.2337/dc25-0728","url":null,"abstract":"OBJECTIVE To identify baseline multiomic and phenotypic predictors and develop prediction models for weight and body composition loss and regain in the Low-Carbohydrate Diet and Time-Restricted Eating (LEAN-TIME) trial. RESEARCH DESIGN AND METHODS A post hoc analysis was conducted of the LEAN-TIME feeding trial using data from 88 adults with overweight/obesity completing a 12-week calorie-restricted weight-loss phase and 79 completing a 28-week weight-regain phase. Baseline dietary, metabolic, fecal metabolome, and gut microbiome data were candidate predictors of changes in weight, body fat mass (BFM), and soft lean mass (SLM). Multivariable regression and the least absolute shrinkage and selection operator model were used to identify predictors and develop weighted-sum prediction models. RESULTS Multiomic and phenotypic models significantly outperformed phenotype-only models (P &lt; 0.05), demonstrating strong predictive performance during both phases. During weight loss, the multiomic and phenotypic model yielded R2 values of 0.49, 0.61, and 0.54 for changes in weight, BFM, and SLM, respectively, with corresponding root mean square errors (RMSEs) of 1.59, 1.41, and 0.98 kg. For binary classification of clinically meaningful weight loss (≥5%), the model achieved an area under the curve of 0.95 (sensitivity 94.12%; specificity 86.79%). During weight regain, R2 values reached 0.72, 0.73, and 0.66 for weight, BFM, and SLM (RMSEs 1.40, 1.62, and 0.73 kg), respectively. Several key baseline predictors, primarily gut microbes and fecal metabolites, such as N-acetyl-l-aspartic acid, Ruminococcus callidus, and Bifidobacterium adolescentis, were shared for weight and body composition changes during both phases. CONCLUSIONS Baseline multiomic and phenotypic data effectively predict weight and body composition loss and regain, offering insights for personalized weight management.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"27 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144520334","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}
Chris Ho Ching Yeung, Alison K. Wright, Daniel P. Windred, Angus C. Burns, Andrew J.K. Phillips, Sean W. Cain, Martin K. Rutter, Qian Xiao
OBJECTIVE Circadian rhythms play a key role in metabolic health. Rest–activity rhythms, which are in part driven by circadian rhythms, may be associated with diabetes risk. There is a need for large prospective studies to comprehensively examine different rest–activity metrics to determine their relative strength in predicting risk of incident type 2 diabetes. RESEARCH DESIGN AND METHODS In actigraphy data from 83,887 UK Biobank participants, we applied both parametric and nonparametric algorithms to derive 13 different metrics characterizing different aspects of rest–activity rhythm. Diabetes cases were identified using both self-reported data and health records. We used Cox proportional hazards models to assess associations between rest–activity parameters and type 2 diabetes risk and random forest models to determine the relative importance of these parameters in risk prediction. RESULTS We found that multiple rest–activity characteristics were predictive of a higher risk of incident diabetes, including lower pseudo-F statistic (hazard ratio [HR] of quintile 1 ([Q1] vs. Q5 1.27; 95% CI 1.09–1.46; Ptrend < 0.001), lower amplitude (HRQ1 vs. Q5 2.56; 95% CI 2.21–2.97; Ptrend < 0.001), lower midline estimating statistic of rhythm (HRQ1 vs. Q5 2.59; 95% CI 2.24–3.00; Ptrend < 0.001), lower relative amplitude (HRQ1 vs. Q5 4.64; 95% CI 3.74–5.76; Ptrend < 0.001), lower M10 (HRQ1 vs. Q5 3.82; 95% CI 3.20–4.55; Ptrend < 0.001), higher L5 (HRQ5 vs. Q1 1.88; 95% CI 1.62–2.19; Ptrend < 0.001), and later L5 start time (HRQ5 vs. Q1 1.20; 95% CI 1.04–1.38; Ptrend = 0.004). Random forest models ranked most of the rest–activity metrics as top predictors of diabetes incidence, when compared with traditional diabetes risk factors. The findings were consistent across subgroups of age, sex, BMI, and shift work status. CONCLUSIONS Rest–activity rhythm characteristics measured from actigraphy data may serve as digital biomarkers for predicting type 2 diabetes risk.
目的：昼夜节律在代谢健康中发挥关键作用。部分由昼夜节律驱动的休息-活动节律可能与糖尿病风险有关。有必要进行大规模的前瞻性研究，以全面检查不同的休息-活动指标，以确定它们在预测2型糖尿病发生风险方面的相对强度。研究设计和方法在83,887名英国生物银行参与者的活动记录数据中，我们应用参数和非参数算法推导出表征休息-活动节律不同方面的13种不同指标。通过自我报告数据和健康记录确定糖尿病病例。我们使用Cox比例风险模型来评估休息-活动参数与2型糖尿病风险之间的关系，并使用随机森林模型来确定这些参数在风险预测中的相对重要性。结果我们发现，多种休息-活动特征可预测较高的糖尿病发生风险，包括五分位数1 （[Q1] vs. Q5）的伪f统计量（风险比[HR]）较低([Q1] vs. Q5 = 1.27；95% ci 1.09-1.46；Ptrend, lt;0.001)，振幅较低(HRQ1 vs. Q5 2.56；95% ci 2.21-2.97；Ptrend, lt;0.001)，心律中线下估计统计量(HRQ1 vs. Q5 2.59；95% ci 2.24-3.00；Ptrend, lt;0.001)，相对振幅较低(HRQ1 vs. Q5 4.64；95% ci 3.74-5.76；Ptrend, lt;0.001)， M10较低(HRQ1 vs. Q5 3.82；95% ci 3.20-4.55；Ptrend, lt;0.001)， L5较高(HRQ5 vs Q1 1.88；95% ci 1.62-2.19；Ptrend, lt;0.001)， L5开始时间较晚(HRQ5 vs. Q1 1.20；95% ci 1.04-1.38；p趋势= 0.004)。与传统的糖尿病风险因素相比，随机森林模型将大多数休息-活动指标列为糖尿病发病率的主要预测因素。这些发现在不同年龄、性别、BMI和轮班工作状态的亚组中是一致的。结论：从活动记录仪数据中测量的休息-活动节律特征可作为预测2型糖尿病风险的数字生物标志物。
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