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。
{"title":"Impaired Rest–Activity Rhythm Characteristics Predict Higher Risk of Incident Type 2 Diabetes in UK Biobank Participants","authors":"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","doi":"10.2337/dc25-0309","DOIUrl":"https://doi.org/10.2337/dc25-0309","url":null,"abstract":"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 &lt; 0.001), lower amplitude (HRQ1 vs. Q5 2.56; 95% CI 2.21–2.97; Ptrend &lt; 0.001), lower midline estimating statistic of rhythm (HRQ1 vs. Q5 2.59; 95% CI 2.24–3.00; Ptrend &lt; 0.001), lower relative amplitude (HRQ1 vs. Q5 4.64; 95% CI 3.74–5.76; Ptrend &lt; 0.001), lower M10 (HRQ1 vs. Q5 3.82; 95% CI 3.20–4.55; Ptrend &lt; 0.001), higher L5 (HRQ5 vs. Q1 1.88; 95% CI 1.62–2.19; Ptrend &lt; 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.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"31 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500380","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}
Kevin Yau, Joel G. Ray, Nivethika Jeyakumar, Bin Luo, Sheikh Abdullah, Eric McArthur, Stephanie N. Dixon, Sara Wing, Kristin K. Clemens, Fabio Castrillon-Ramirez, Jacob A. Udell, Alejandro Meraz-Munoz, Ann Young, Ziv Harel, Jeffrey Perl, Vikas S. Sridhar, Huajing Ni, Tae Won Yi, Lawrence A. Leiter, Amit X. Garg, David Z.I. Cherney, Ron Wald
OBJECTIVE The aim of this study was to evaluate the effect of glucagon-like peptide 1 receptor agonist (GLP-1RA) versus dipeptidyl peptidase 4 inhibitor (DPP4i) initiation on emergency department (ED) visits and all-cause hospitalizations across the spectrum of kidney disease. RESEARCH DESIGN AND METHODS This was a retrospective population-based observational cohort study in adults with an estimated glomerular filtration rate <90 mL/min/1.73 m2 using inverse probability of treatment weighting. The Prentice-Williams-Peterson (PWP) gap time model was used for the primary analysis. RESULTS The cohort included 24,576 new users of a GLP-1RA and 23,600 DPP4i new users. GLP1RA initiation was associated with a lower risk of all-cause ED encounters or hospitalizations (hazard ratio [HR] 0.90; 95% CI 0.87–0.94; P < 0.0001). This finding was consistent in confirmatory analyses using the Andersen-Gill model and the PWP calendar time model. CONCLUSIONS GLP-1RA initiation was associated with a reduction in all-cause ED visits and hospitalizations compared with new use of a DPP4i.
目的：本研究的目的是评估胰高血糖素样肽1受体激动剂（GLP-1RA）与二肽基肽酶4抑制剂（DPP4i）启动对急诊科（ED）就诊和全因肾病住院的影响。研究设计和方法：这是一项基于人群的回顾性观察队列研究，研究对象为肾小球滤过率为90 mL/min/1.73 m2的成人，采用治疗加权逆概率法。采用Prentice-Williams-Peterson （PWP）间隙时间模型进行初步分析。该队列包括24,576名GLP-1RA新用户和23,600名DPP4i新用户。GLP1RA起始与全因ED遭遇或住院的风险较低相关(风险比[HR] 0.90；95% ci 0.87-0.94；P, lt;0.0001)。这一发现在使用Andersen-Gill模型和PWP日历时间模型的验证分析中是一致的。结论：与新使用DPP4i相比，GLP-1RA启动与全因ED就诊和住院次数减少有关。
{"title":"Glucagon-Like Peptide 1 Receptor Agonists and the Risk of Emergency Department Visits and Hospitalization in Patients With Chronic Kidney Disease","authors":"Kevin Yau, Joel G. Ray, Nivethika Jeyakumar, Bin Luo, Sheikh Abdullah, Eric McArthur, Stephanie N. Dixon, Sara Wing, Kristin K. Clemens, Fabio Castrillon-Ramirez, Jacob A. Udell, Alejandro Meraz-Munoz, Ann Young, Ziv Harel, Jeffrey Perl, Vikas S. Sridhar, Huajing Ni, Tae Won Yi, Lawrence A. Leiter, Amit X. Garg, David Z.I. Cherney, Ron Wald","doi":"10.2337/dc24-2811","DOIUrl":"https://doi.org/10.2337/dc24-2811","url":null,"abstract":"OBJECTIVE The aim of this study was to evaluate the effect of glucagon-like peptide 1 receptor agonist (GLP-1RA) versus dipeptidyl peptidase 4 inhibitor (DPP4i) initiation on emergency department (ED) visits and all-cause hospitalizations across the spectrum of kidney disease. RESEARCH DESIGN AND METHODS This was a retrospective population-based observational cohort study in adults with an estimated glomerular filtration rate &lt;90 mL/min/1.73 m2 using inverse probability of treatment weighting. The Prentice-Williams-Peterson (PWP) gap time model was used for the primary analysis. RESULTS The cohort included 24,576 new users of a GLP-1RA and 23,600 DPP4i new users. GLP1RA initiation was associated with a lower risk of all-cause ED encounters or hospitalizations (hazard ratio [HR] 0.90; 95% CI 0.87–0.94; P &lt; 0.0001). This finding was consistent in confirmatory analyses using the Andersen-Gill model and the PWP calendar time model. CONCLUSIONS GLP-1RA initiation was associated with a reduction in all-cause ED visits and hospitalizations compared with new use of a DPP4i.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"22 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500442","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}
Jeffrey S. Gonzalez, Claire J. Hoogendoorn, Raymond Hernandez, Stefan Schneider, Fayel Mustafiz, Megha Siddhanta, Elizabeth A. Pyatak
OBJECTIVE In an observational study, we paired ecological momentary assessment (EMA) and continuous glucose monitoring (CGM) to examine lagged effects of glycemic regulation on diabetes-related distress (DD), and vice versa, among adults with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS Participants (N = 182; median ± SD age 40 ± 14 years; 54% women; 41% Latino; 29% White and 15% Black) wore a blinded CGM device for 14 days and completed five to six EMA surveys per day. We tested expected associations between momentary DD ratings and relevant patient-reported outcomes on validated questionnaires. Using multilevel cross-lagged modeling, we evaluated within-person lagged effects of CGM metrics (mean glucose mean; percentage of time in range [TIR; i.e., 70–180 mg/dL] and percentages of time 181–250, >250, and <70 mg/dL; and coefficient of variation [CV]) over 3-h periods on DD rated 0–100 at the end of that interval and 3 h later. We also examined lagged effects of DD on subsequent CGM metrics. RESULTS Momentary DD ratings were significantly associated with results of questionnaires for DD, well-being, functional and mental health, and quality of life. Higher mean glucose, less TIR, greater percentage of time 181–250 and >250 mg/dL, and higher CV over 3 h each predicted greater DD at the end of that interval; higher 3-h mean glucose also predicted more DD 3 h later (P < 0.05). Greater DD unexpectedly predicted a lower percentage of time in hypoglycemia over the next 3 h (P < 0.05) but predicted no other CGM metrics. CONCLUSIONS Findings support the validity of EMA of DD in adults with T1D and suggest glucose dysregulation is linked to subsequent increased DD over the short term, not vice versa. These findings have implications for interventions targeting DD.
{"title":"Diabetes-Related Distress and Glycemic Dysregulation in Everyday Life With Type 1 Diabetes: Which Comes First?","authors":"Jeffrey S. Gonzalez, Claire J. Hoogendoorn, Raymond Hernandez, Stefan Schneider, Fayel Mustafiz, Megha Siddhanta, Elizabeth A. Pyatak","doi":"10.2337/dc25-0559","DOIUrl":"https://doi.org/10.2337/dc25-0559","url":null,"abstract":"OBJECTIVE In an observational study, we paired ecological momentary assessment (EMA) and continuous glucose monitoring (CGM) to examine lagged effects of glycemic regulation on diabetes-related distress (DD), and vice versa, among adults with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS Participants (N = 182; median ± SD age 40 ± 14 years; 54% women; 41% Latino; 29% White and 15% Black) wore a blinded CGM device for 14 days and completed five to six EMA surveys per day. We tested expected associations between momentary DD ratings and relevant patient-reported outcomes on validated questionnaires. Using multilevel cross-lagged modeling, we evaluated within-person lagged effects of CGM metrics (mean glucose mean; percentage of time in range [TIR; i.e., 70–180 mg/dL] and percentages of time 181–250, &gt;250, and &lt;70 mg/dL; and coefficient of variation [CV]) over 3-h periods on DD rated 0–100 at the end of that interval and 3 h later. We also examined lagged effects of DD on subsequent CGM metrics. RESULTS Momentary DD ratings were significantly associated with results of questionnaires for DD, well-being, functional and mental health, and quality of life. Higher mean glucose, less TIR, greater percentage of time 181–250 and &gt;250 mg/dL, and higher CV over 3 h each predicted greater DD at the end of that interval; higher 3-h mean glucose also predicted more DD 3 h later (P &lt; 0.05). Greater DD unexpectedly predicted a lower percentage of time in hypoglycemia over the next 3 h (P &lt; 0.05) but predicted no other CGM metrics. CONCLUSIONS Findings support the validity of EMA of DD in adults with T1D and suggest glucose dysregulation is linked to subsequent increased DD over the short term, not vice versa. These findings have implications for interventions targeting DD.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"17 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144479185","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}
Barbara H. Braffett, Tore Julsrud Berg, Malin Zimmerman, Kasper Olesen, Søren Gregersen, Michael R. Krogsgaard, Lars B. Dahlin, Kirsten Nørgaard
Upper-limb complications (ULCs) in diabetes, affecting joints, tendons, muscles, connective tissue, nerves, and skin, are underrecognized but prevalent conditions in type 1 and type 2 diabetes. Advances in diabetes care have extended life expectancy, leading to an aging population with diabetes with increased susceptibility to long-term complications beyond traditional vascular issues. Despite some data on ULCs epidemiology, understanding of their pathogenesis, prevention, and impact on quality of life remains limited, and treatments are often based on clinical experience rather than robust evidence. ULCs, including frozen shoulder, trigger finger, carpal tunnel syndrome, ulnar nerve entrapment, Dupuytren disease with contracture, and limited joint mobility, occur two to three times more frequently in diabetes, with higher rates in individuals aged>50 years and those with longer diabetes duration. Chronic hyperglycemia, glycation of collagen, and low-grade inflammation are hypothesized contributors. Modifiable risk factors include poor glycemic control, smoking, and obesity. Individuals with diabetes face slower symptom resolution, higher recurrence rates, and a greater likelihood of bilateral or multiple conditions. Awareness among clinicians and patients is critical, with emphasis on routine screening and proactive management. Early diagnosis, patient education, and targeted interventions can mitigate long-term complications and improve quality of life. Future guidelines should integrate ULC monitoring into routine diabetes care and prioritize clinical trials to establish evidence-based management strategies. Addressing ULCs comprehensively will enhance outcomes for individuals with diabetes, ensuring better functional health and reduced societal burden.
{"title":"Upper-Limb Complications in Diabetes: A Narrative Review","authors":"Barbara H. Braffett, Tore Julsrud Berg, Malin Zimmerman, Kasper Olesen, Søren Gregersen, Michael R. Krogsgaard, Lars B. Dahlin, Kirsten Nørgaard","doi":"10.2337/dci25-0012","DOIUrl":"https://doi.org/10.2337/dci25-0012","url":null,"abstract":"Upper-limb complications (ULCs) in diabetes, affecting joints, tendons, muscles, connective tissue, nerves, and skin, are underrecognized but prevalent conditions in type 1 and type 2 diabetes. Advances in diabetes care have extended life expectancy, leading to an aging population with diabetes with increased susceptibility to long-term complications beyond traditional vascular issues. Despite some data on ULCs epidemiology, understanding of their pathogenesis, prevention, and impact on quality of life remains limited, and treatments are often based on clinical experience rather than robust evidence. ULCs, including frozen shoulder, trigger finger, carpal tunnel syndrome, ulnar nerve entrapment, Dupuytren disease with contracture, and limited joint mobility, occur two to three times more frequently in diabetes, with higher rates in individuals aged&gt;50 years and those with longer diabetes duration. Chronic hyperglycemia, glycation of collagen, and low-grade inflammation are hypothesized contributors. Modifiable risk factors include poor glycemic control, smoking, and obesity. Individuals with diabetes face slower symptom resolution, higher recurrence rates, and a greater likelihood of bilateral or multiple conditions. Awareness among clinicians and patients is critical, with emphasis on routine screening and proactive management. Early diagnosis, patient education, and targeted interventions can mitigate long-term complications and improve quality of life. Future guidelines should integrate ULC monitoring into routine diabetes care and prioritize clinical trials to establish evidence-based management strategies. Addressing ULCs comprehensively will enhance outcomes for individuals with diabetes, ensuring better functional health and reduced societal burden.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"16 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144370511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yu Mi Kang, Robert P. Giugliano, Xinhui Ran, Prakash Deedwania, Gaetano M. De Ferrari, Jyothis T. George, Ioanna Gouni-Berthold, Gabriel Paiva da Silva Lima, Yehuda Handelsman, Basil S. Lewis, E. Magnus Ohman, Huei Wang, J. Antonio G. López, Maria Laura Monsalvo, Marc S. Sabatine, Lawrence A. Leiter
OBJECTIVE To evaluate the clinical efficacy of intensive LDL cholesterol (LDL-C) lowering in type 1 diabetes mellitus (T1DM). RESEARCH DESIGN AND METHODS Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER) randomized participants with atherosclerotic cardiovascular disease (ASCVD) on statins to evolocumab or placebo (median follow-up 2.2 years). The primary end point (PEP) was cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. RESULTS Of 27,564 participants, 10,834 (39.3%) had type 2 diabetes mellitus (T2DM), and 197 (0.7%) had T1DM. In the placebo arm, there was a stepwise increase in the 2.5-year PEP Kaplan-Meier rate from 11.0% to 15.2% to 20.4% in participants with no diabetes, T2DM, and T1DM, respectively (P < 0.0001). Hazard ratios for PEP with evolocumab were 0.87 (95% CI 0.79–0.96), 0.84 (0.75–0.93), and 0.66 (0.32–1.38) in the no diabetes, T2DM, and T1DM groups, and absolute risk reduction was 1.3%, 2.5%, and 7.3%, respectively. CONCLUSIONS Intensive LDL-C lowering may provide substantial clinical benefit in individuals with T1DM and ASCVD. Additional randomized controlled cardiovascular outcomes trials are needed in this population.
目的评价强化降LDL- c治疗1型糖尿病（T1DM）的临床疗效。研究设计和方法：在高风险受试者（FOURIER）中进一步进行PCSK9抑制的心血管结局研究，将接受他汀类药物治疗的动脉粥样硬化性心血管疾病（ASCVD）患者随机分为evolocumab或安慰剂（中位随访时间为2.2年）。主要终点（PEP）是心血管死亡、心肌梗死、中风、不稳定型心绞痛住院或冠状动脉血运重建术。结果在27,564名参与者中，10,834名（39.3%）患有2型糖尿病（T2DM）， 197名（0.7%）患有T1DM。在安慰剂组中，无糖尿病、2型糖尿病和1型糖尿病患者的2.5年PEP Kaplan-Meier率分别从11.0%逐步增加到15.2%和20.4% (P <；0.0001)。在无糖尿病、T2DM和T1DM组，PEP与evolocumab的风险比分别为0.87 （95% CI 0.79-0.96）、0.84（0.75-0.93）和0.66(0.32-1.38)，绝对风险降低分别为1.3%、2.5%和7.3%。结论：强化LDL-C降低可能为T1DM和ASCVD患者提供实质性的临床益处。需要在这一人群中进行额外的随机对照心血管结局试验。
{"title":"Cardiovascular Outcomes and Efficacy of the PCSK9 Inhibitor Evolocumab in Individuals With Type 1 Diabetes: Insights From the FOURIER Trial","authors":"Yu Mi Kang, Robert P. Giugliano, Xinhui Ran, Prakash Deedwania, Gaetano M. De Ferrari, Jyothis T. George, Ioanna Gouni-Berthold, Gabriel Paiva da Silva Lima, Yehuda Handelsman, Basil S. Lewis, E. Magnus Ohman, Huei Wang, J. Antonio G. López, Maria Laura Monsalvo, Marc S. Sabatine, Lawrence A. Leiter","doi":"10.2337/dc25-0942","DOIUrl":"https://doi.org/10.2337/dc25-0942","url":null,"abstract":"OBJECTIVE To evaluate the clinical efficacy of intensive LDL cholesterol (LDL-C) lowering in type 1 diabetes mellitus (T1DM). RESEARCH DESIGN AND METHODS Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER) randomized participants with atherosclerotic cardiovascular disease (ASCVD) on statins to evolocumab or placebo (median follow-up 2.2 years). The primary end point (PEP) was cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. RESULTS Of 27,564 participants, 10,834 (39.3%) had type 2 diabetes mellitus (T2DM), and 197 (0.7%) had T1DM. In the placebo arm, there was a stepwise increase in the 2.5-year PEP Kaplan-Meier rate from 11.0% to 15.2% to 20.4% in participants with no diabetes, T2DM, and T1DM, respectively (P &lt; 0.0001). Hazard ratios for PEP with evolocumab were 0.87 (95% CI 0.79–0.96), 0.84 (0.75–0.93), and 0.66 (0.32–1.38) in the no diabetes, T2DM, and T1DM groups, and absolute risk reduction was 1.3%, 2.5%, and 7.3%, respectively. CONCLUSIONS Intensive LDL-C lowering may provide substantial clinical benefit in individuals with T1DM and ASCVD. Additional randomized controlled cardiovascular outcomes trials are needed in this population.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"9 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144341055","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}
Mariana P. Socal, Namratha R. Kandula, Pineal I. Bareamichael, Jeromie Ballreich, Ilina Odouard, So-Yeon Kang, Joy O. Acha, Kelly E. Anderson, Michael DiStefano, Fernando Gerchman, Joseph F. Levy
Unaffordability of pharmaceutical treatments remains as a critical barrier to diabetes care in the U.S. Through a synthesis of recent evidence on affordability of diabetes drugs, with particular attention to emergent reforms, this call for action focuses on structural solutions to improve the affordability of pharmaceutical treatments for diabetes in the U.S. that providers should be aware of and consider supporting. Incentivizing competition in biosimilars and generics markets, increasing transparency, reforming pricing models that influence drug coverage, and expanding federal negotiation of drug prices, among other actions, can help make prescription drugs more affordable for patients, reduce budgetary impacts on payors, and increase access, ultimately helping to improve the health of all Americans living with diabetes.
{"title":"Improving Affordability of Pharmaceutical Treatments for Diabetes: A Call for Action","authors":"Mariana P. Socal, Namratha R. Kandula, Pineal I. Bareamichael, Jeromie Ballreich, Ilina Odouard, So-Yeon Kang, Joy O. Acha, Kelly E. Anderson, Michael DiStefano, Fernando Gerchman, Joseph F. Levy","doi":"10.2337/dci25-0002","DOIUrl":"https://doi.org/10.2337/dci25-0002","url":null,"abstract":"Unaffordability of pharmaceutical treatments remains as a critical barrier to diabetes care in the U.S. Through a synthesis of recent evidence on affordability of diabetes drugs, with particular attention to emergent reforms, this call for action focuses on structural solutions to improve the affordability of pharmaceutical treatments for diabetes in the U.S. that providers should be aware of and consider supporting. Incentivizing competition in biosimilars and generics markets, increasing transparency, reforming pricing models that influence drug coverage, and expanding federal negotiation of drug prices, among other actions, can help make prescription drugs more affordable for patients, reduce budgetary impacts on payors, and increase access, ultimately helping to improve the health of all Americans living with diabetes.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"632 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Neda Rasouli, Ecenur Guder Arslan, Andrei-Mircea Catarig, Kim Houlind, Bernhard Ludvik, Joakim Nordanstig, Harald Sourij, Sebastian Thomas, Subodh Verma, Marc P. Bonaca
OBJECTIVE The Semaglutide and Walking Capacity in People with Symptomatic Peripheral Artery Disease and Type 2 Diabetes (STRIDE) trial (NCT04560998) showed that once-weekly subcutaneous semaglutide 1.0 mg significantly improved functional outcomes, symptoms, and quality of life in individuals with symptomatic peripheral artery disease (PAD) and type 2 diabetes. Whether these benefits are consistent across diabetes-related characteristics remains unclear. RESEARCH DESIGN AND METHODS The primary outcome was the ratio to baseline (ETR) in maximum walking distance (MWD), with pain-free walking distance (PFWD) as a key secondary end point. Both were measured at 52 weeks using a constant load treadmill. Subgroup analyses were performed by diabetes duration, BMI, HbA1c, and diabetes medications. A mixed model for repeated measurements was used, incorporating treatment, region, and subgroup as fixed factors, and baseline value as covariate, along with the treatment-by-subgroup interaction. RESULTS Among 792 participants (median diabetes duration 12.2 years, HbA1c 7.1%, and BMI 28.7 kg/m2), 35.1% used sodium–glucose cotransporter 2 inhibitors and 31.7% used insulin. Semaglutide significantly improved MWD regardless of diabetes duration (ETR of 1.15 vs. 1.13 for <10 vs. ≥10 years, P = 0.80), BMI (1.12 vs. 1.16 for <30 vs. ≥30 kg/m2, P = 0.58), HbA1c (1.13 for <7% and ≥7%, P = 0.99), or medication use. Semaglutide also improved PFWD across subgroups (P > 0.1 for all interactions). BMI reduction correlated weakly with MWD improvements and was more pronounced in the controls with higher baseline BMI. Safety outcomes were consistent across subgroups. CONCLUSIONS Semaglutide improved walking function in people with PAD and type 2 diabetes, including nonobese individuals and those with well-controlled HbA1c. Benefits were consistent across BMI and HbA1c categories, supporting effectiveness beyond weight or glycemic changes.
目的：有症状的外周动脉疾病和2型糖尿病患者的塞马鲁肽和行走能力（STRIDE）试验（NCT04560998）显示，每周一次皮下注射塞马鲁肽1.0 mg可显著改善有症状的外周动脉疾病（PAD）和2型糖尿病患者的功能结局、症状和生活质量。这些益处在糖尿病相关特征中是否一致仍不清楚。研究设计和方法主要终点是最大步行距离（MWD）与基线的比值（ETR），无痛步行距离（PFWD）作为关键的次要终点。在52周时使用恒定负荷跑步机进行测量。根据糖尿病病程、BMI、HbA1c和糖尿病药物进行亚组分析。使用重复测量的混合模型，将治疗、地区和亚组作为固定因素，基线值作为协变量，以及治疗与亚组之间的相互作用。结果：在792名参与者中（糖尿病病程中位数为12.2年，HbA1c为7.1%，BMI为28.7 kg/m2）， 35.1%使用钠-葡萄糖共转运蛋白2抑制剂，31.7%使用胰岛素。无论糖尿病病程（ETR为1.15 vs. 1.13, 10年vs.≥10年，P = 0.80）、BMI（30年vs.≥30 kg/m2， ETR为1.12 vs. 1.16, P = 0.58）、HbA1c（7%和≥7%，P = 0.99）或用药情况如何，Semaglutide均显著改善了MWD。Semaglutide还改善了各亚组的PFWD (P >；0.1表示所有交互)。BMI降低与MWD改善的相关性较弱，在基线BMI较高的对照组中更为明显。各亚组的安全性结果一致。结论：Semaglutide改善了PAD和2型糖尿病患者的行走功能，包括非肥胖个体和HbA1c控制良好的患者。在BMI和HbA1c类别中，益处是一致的，支持了体重或血糖变化之外的有效性。
{"title":"Benefit of Semaglutide in Symptomatic Peripheral Artery Disease by Baseline Type 2 Diabetes Characteristics: Insights From STRIDE, a Randomized, Placebo-Controlled, Double-Blind Trial","authors":"Neda Rasouli, Ecenur Guder Arslan, Andrei-Mircea Catarig, Kim Houlind, Bernhard Ludvik, Joakim Nordanstig, Harald Sourij, Sebastian Thomas, Subodh Verma, Marc P. Bonaca","doi":"10.2337/dc25-1082","DOIUrl":"https://doi.org/10.2337/dc25-1082","url":null,"abstract":"OBJECTIVE The Semaglutide and Walking Capacity in People with Symptomatic Peripheral Artery Disease and Type 2 Diabetes (STRIDE) trial (NCT04560998) showed that once-weekly subcutaneous semaglutide 1.0 mg significantly improved functional outcomes, symptoms, and quality of life in individuals with symptomatic peripheral artery disease (PAD) and type 2 diabetes. Whether these benefits are consistent across diabetes-related characteristics remains unclear. RESEARCH DESIGN AND METHODS The primary outcome was the ratio to baseline (ETR) in maximum walking distance (MWD), with pain-free walking distance (PFWD) as a key secondary end point. Both were measured at 52 weeks using a constant load treadmill. Subgroup analyses were performed by diabetes duration, BMI, HbA1c, and diabetes medications. A mixed model for repeated measurements was used, incorporating treatment, region, and subgroup as fixed factors, and baseline value as covariate, along with the treatment-by-subgroup interaction. RESULTS Among 792 participants (median diabetes duration 12.2 years, HbA1c 7.1%, and BMI 28.7 kg/m2), 35.1% used sodium–glucose cotransporter 2 inhibitors and 31.7% used insulin. Semaglutide significantly improved MWD regardless of diabetes duration (ETR of 1.15 vs. 1.13 for &lt;10 vs. ≥10 years, P = 0.80), BMI (1.12 vs. 1.16 for &lt;30 vs. ≥30 kg/m2, P = 0.58), HbA1c (1.13 for &lt;7% and ≥7%, P = 0.99), or medication use. Semaglutide also improved PFWD across subgroups (P &gt; 0.1 for all interactions). BMI reduction correlated weakly with MWD improvements and was more pronounced in the controls with higher baseline BMI. Safety outcomes were consistent across subgroups. CONCLUSIONS Semaglutide improved walking function in people with PAD and type 2 diabetes, including nonobese individuals and those with well-controlled HbA1c. Benefits were consistent across BMI and HbA1c categories, supporting effectiveness beyond weight or glycemic changes.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"26 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337510","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}
Marshall H. Chin, Joseph D. Bruch, Colleen M. Grogan, Elbert S. Huang, Namratha R. Kandula, David D. Kim, Monica E. Peek, Harold A. Pollack
The U.S. health care system is broken, with particularly low performance for health outcomes, access to care, equity, and administrative efficiency in comparison with other high-income countries, despite high cost. By virtue of the many elements required for optimal care, the poor diabetes care quality and outcome metrics of the U.S. are canaries in the coal mine for the health care system. The fundamental problem with the U.S. health care system is that it does not prioritize the long-term health and well-being of all individuals and communities. Three intertwined elements are foundational for an understanding of why the U.S. health care system is built the way it is and what changes are necessary to improve it: 1) ethics and culture; 2) political economy, the underlying political and economic structures that shape our nation and thus our health system; and 3) the definition and measurement of value in health care. This article recommends that health care policies around health insurance and payment be designed to support, incentivize, and sustain effective population health models that address medical, social, psychological, and behavioral needs of all individuals and communities. Good governance is essential to assure that payer and provider market incentives are explicitly aligned to prioritize the health and well-being of individuals and communities and cost-effectiveness of care, beyond short-term financial gain for health care systems and investors. Equitable access allows for health care resource distribution according to need, enabling all individuals to have a fair and just opportunity for health.
{"title":"How to Fix a Broken Health Care System: Pathways to Maximize Health and Well-being for All","authors":"Marshall H. Chin, Joseph D. Bruch, Colleen M. Grogan, Elbert S. Huang, Namratha R. Kandula, David D. Kim, Monica E. Peek, Harold A. Pollack","doi":"10.2337/dci25-0001","DOIUrl":"https://doi.org/10.2337/dci25-0001","url":null,"abstract":"The U.S. health care system is broken, with particularly low performance for health outcomes, access to care, equity, and administrative efficiency in comparison with other high-income countries, despite high cost. By virtue of the many elements required for optimal care, the poor diabetes care quality and outcome metrics of the U.S. are canaries in the coal mine for the health care system. The fundamental problem with the U.S. health care system is that it does not prioritize the long-term health and well-being of all individuals and communities. Three intertwined elements are foundational for an understanding of why the U.S. health care system is built the way it is and what changes are necessary to improve it: 1) ethics and culture; 2) political economy, the underlying political and economic structures that shape our nation and thus our health system; and 3) the definition and measurement of value in health care. This article recommends that health care policies around health insurance and payment be designed to support, incentivize, and sustain effective population health models that address medical, social, psychological, and behavioral needs of all individuals and communities. Good governance is essential to assure that payer and provider market incentives are explicitly aligned to prioritize the health and well-being of individuals and communities and cost-effectiveness of care, beyond short-term financial gain for health care systems and investors. Equitable access allows for health care resource distribution according to need, enabling all individuals to have a fair and just opportunity for health.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"5 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337512","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}
Sharmin Shabnam, Suping Ling, Clare Gillies, Francesco Zaccardi, Pratik Choudhary, Kamlesh Khunti, Samuel Seidu
OBJECTIVE To estimate the association among glucose control, sulfonylureas, and insulin treatment with the risk of hospitalization for falls and fractures in older adults with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS This observational cohort study used U.K. Clinical Practice Research Datalink GOLD data linked to hospital and death records. Older adults (≥70 years) with T2D, identified between 2000 and 2017, were considered exposed if they had three consecutive HbA1c measurements <7% (53 mmol/mol) while receiving treatment with insulin or sulfonylureas. Each exposed individual was matched with to three nonexposed individuals. Outcomes included hospitalizations for falls and fractures. Flexible parametric survival models, adjusted for sociodemographic and clinical factors, and associated estimated relative (hazard ratio [HR]) and absolute risks. RESULTS Among 21,365 individuals (n = 5,833 [27.3%] in the exposed group), the adjusted relative risks of hospitalization for falls and fractures were marginally higher compared with those nonexposed (HR 1.04 [95% CI 0.96–1.11] and 1.07 [95% CI 0.97–1.17], respectively). The 10-year absolute risk values of hospitalization for falls were slightly higher in the exposed (range 15.6–36.8% in those aged 70–85 years) than nonexposed (15.1–36.0%) individuals. Absolute risk differences remained minimal (0.2–0.6% at 5 years and 0.5–0.8% at 10 years). CONCLUSIONS We found no evidence of an association between sustained HbA1c <7% while receiving insulin or sulfonylurea therapy and clinically meaningful increased risks of falls or fractures in older adults with T2D. Clinicians should continue to balance the benefits of glycemic control with the risks of complications in older adults.
目的评估血糖控制、磺脲类药物和胰岛素治疗与老年2型糖尿病（T2D）患者因跌倒和骨折住院风险之间的关系。研究设计和方法本观察性队列研究使用了英国临床实践研究数据链GOLD与医院和死亡记录相关的数据。2000年至2017年期间发现的老年（≥70岁）T2D患者，如果在接受胰岛素或磺脲类药物治疗期间连续三次HbA1c测量≥7% (53 mmol/mol)，则视为暴露。每个暴露的个体与三个未暴露的个体相匹配。结果包括因跌倒和骨折住院。灵活的参数生存模型，调整了社会人口和临床因素，以及相关的估计相对（危险比[HR]）和绝对风险。结果：在21,365例患者中（暴露组n = 5,833例[27.3%]），因跌倒和骨折住院的调整相对风险比未暴露组略高（HR分别为1.04 [95% CI 0.96-1.11]和1.07 [95% CI 0.97-1.17]）。暴露者因跌倒住院的10年绝对风险值（70-85岁人群15.6-36.8%）略高于未暴露者（15.1-36.0%）。绝对风险差异仍然很小（5年为0.2-0.6%，10年为0.5-0.8%）。结论：我们没有发现证据表明接受胰岛素或磺脲类药物治疗的老年T2D患者HbA1c≥7%与临床上有意义的跌倒或骨折风险增加之间存在关联。临床医生应继续平衡老年人血糖控制的益处和并发症的风险。
{"title":"Glucose Control, Sulfonylureas, and Insulin Treatment in Older Adults With Type 2 Diabetes and Risk of Falls and Fractures: An Observational Study","authors":"Sharmin Shabnam, Suping Ling, Clare Gillies, Francesco Zaccardi, Pratik Choudhary, Kamlesh Khunti, Samuel Seidu","doi":"10.2337/dc25-0517","DOIUrl":"https://doi.org/10.2337/dc25-0517","url":null,"abstract":"OBJECTIVE To estimate the association among glucose control, sulfonylureas, and insulin treatment with the risk of hospitalization for falls and fractures in older adults with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS This observational cohort study used U.K. Clinical Practice Research Datalink GOLD data linked to hospital and death records. Older adults (≥70 years) with T2D, identified between 2000 and 2017, were considered exposed if they had three consecutive HbA1c measurements &lt;7% (53 mmol/mol) while receiving treatment with insulin or sulfonylureas. Each exposed individual was matched with to three nonexposed individuals. Outcomes included hospitalizations for falls and fractures. Flexible parametric survival models, adjusted for sociodemographic and clinical factors, and associated estimated relative (hazard ratio [HR]) and absolute risks. RESULTS Among 21,365 individuals (n = 5,833 [27.3%] in the exposed group), the adjusted relative risks of hospitalization for falls and fractures were marginally higher compared with those nonexposed (HR 1.04 [95% CI 0.96–1.11] and 1.07 [95% CI 0.97–1.17], respectively). The 10-year absolute risk values of hospitalization for falls were slightly higher in the exposed (range 15.6–36.8% in those aged 70–85 years) than nonexposed (15.1–36.0%) individuals. Absolute risk differences remained minimal (0.2–0.6% at 5 years and 0.5–0.8% at 10 years). CONCLUSIONS We found no evidence of an association between sustained HbA1c &lt;7% while receiving insulin or sulfonylurea therapy and clinically meaningful increased risks of falls or fractures in older adults with T2D. Clinicians should continue to balance the benefits of glycemic control with the risks of complications in older adults.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"5 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319863","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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