首页 > 最新文献

Diabetes, Obesity & Metabolism最新文献

英文 中文
Diabetes, Obesity and Metabolism 糖尿病、肥胖和新陈代谢
IF 5.7 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-01-14 DOI: 10.1111/dom.70423
{"title":"Diabetes, Obesity and Metabolism","authors":"","doi":"10.1111/dom.70423","DOIUrl":"https://doi.org/10.1111/dom.70423","url":null,"abstract":"","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":"28 2","pages":"797-798"},"PeriodicalIF":5.7,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://dom-pubs.onlinelibrary.wiley.com/doi/epdf/10.1111/dom.70423","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145986995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Reallocating morning physical activity to later-day activity and its association with type 2 diabetes incidence: The Maastricht Study. 马斯特里赫特研究:将早晨的体力活动重新分配到晚上的体力活动及其与2型糖尿病发病率的关系
IF 5.7 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-01-13 DOI: 10.1111/dom.70438
Marvin Y Chong, Simone J P M Eussen, Jeroen H P M van der Velde, Bastiaan E de Galan, Hans H C M Savelberg, Hans Bosma, Martijn J L Bours, Matty P Weijenberg, Annemarie Koster

Aims: The timing of physical activity may influence metabolic health through interactions with circadian rhythms, yet its role in type 2 diabetes mellitus (T2DM) development is unclear. We investigated associations between time-of-day-specific physical activity and incident T2DM, and whether theoretically reallocating activity from morning to later in the day was associated with changes in T2DM risk.

Materials and methods: We included 4615 participants from The Maastricht Study cohort without diabetes (age 59.2 ± 8.6 years; 56.3% women). Device-based physical activity was measured over 7 days using activPAL monitors and classified into light-intensity physical activity (LPA) and moderate-to-vigorous intensity physical activity (MVPA), for morning (06:00-11:59 AM), afternoon (12:00-17:59 PM), evening (18:00-23:59 PM) and night (00:00-05:59 AM). Incident T2DM was assessed during a median 8.2-year follow-up. Cox proportional hazard and isotemporal substitution models were used, adjusted for sociodemographic and lifestyle factors, including diet, employment and sleep duration.

Results: During follow-up, 168 participants (3.6%) developed T2DM. Each additional 10 min/day of afternoon LPA or MVPA was associated with lower T2DM risk (LPA: hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.70-0.97; MVPA: HR 0.85, 95% CI 0.72-1.00). Evening MVPA was also inversely associated with T2DM risk (0.65; 0.45-0.93), whereas night-time MVPA was associated with an increased risk (3.64; 1.30-10.17). No significant associations were found of morning LPA and MVPA or evening and night LPA with T2DM incidence. Substitution analyses indicated that reallocating 10 min of morning LPA to afternoon LPA (HR 0.71; 0.54-0.95) or morning MVPA to evening MVPA (HR: 0.64; 0.43-0.96) was associated with a lower T2DM risk, while no other significant associations were observed.

Conclusions: Later-day physical activity, particularly in the afternoon, was associated with a lower incidence of T2DM, independent of intensity. This highlights the potential relevance of activity timing in relation to T2DM incidence.

目的:体育活动的时间可能通过与昼夜节律的相互作用影响代谢健康,但其在2型糖尿病(T2DM)发展中的作用尚不清楚。我们调查了一天中特定时间的身体活动与T2DM事件之间的关系,以及理论上是否将活动从早晨重新分配到一天中的晚些时候与T2DM风险的变化有关。材料和方法:我们从马斯特里赫特研究队列中纳入了4615名无糖尿病的参与者(年龄59.2±8.6岁,56.3%为女性)。使用activPAL监测仪在7天内测量基于设备的身体活动,并将其分为轻强度身体活动(LPA)和中高强度身体活动(MVPA),分别为早上(06:00-11:59 AM)、下午(12:00-17:59 PM)、晚上(18:00-23:59 PM)和晚上(00:00-05:59 AM)。在中位8.2年的随访期间评估T2DM事件。使用Cox比例风险和等时间替代模型,调整了社会人口统计学和生活方式因素,包括饮食、就业和睡眠时间。结果:随访期间,168名参与者(3.6%)发展为T2DM。每天下午LPA或MVPA每增加10分钟与T2DM风险降低相关(LPA:风险比[HR] 0.82, 95%可信区间[CI] 0.70-0.97; MVPA: HR 0.85, 95% CI 0.72-1.00)。夜间MVPA也与T2DM风险呈负相关(0.65;0.45-0.93),而夜间MVPA与风险增加相关(3.64;1.30-10.17)。没有发现早晨LPA和MVPA或傍晚和夜间LPA与T2DM发病率有显著关联。替代分析表明,将上午10分钟的LPA重新分配到下午LPA (HR: 0.71; 0.54-0.95)或将上午MVPA重新分配到晚上MVPA (HR: 0.64; 0.43-0.96)与较低的T2DM风险相关,但未观察到其他显著相关性。结论:晚些时候的体力活动,特别是下午的体力活动,与较低的T2DM发病率相关,与强度无关。这突出了活动时间与T2DM发病率的潜在相关性。
{"title":"Reallocating morning physical activity to later-day activity and its association with type 2 diabetes incidence: The Maastricht Study.","authors":"Marvin Y Chong, Simone J P M Eussen, Jeroen H P M van der Velde, Bastiaan E de Galan, Hans H C M Savelberg, Hans Bosma, Martijn J L Bours, Matty P Weijenberg, Annemarie Koster","doi":"10.1111/dom.70438","DOIUrl":"https://doi.org/10.1111/dom.70438","url":null,"abstract":"<p><strong>Aims: </strong>The timing of physical activity may influence metabolic health through interactions with circadian rhythms, yet its role in type 2 diabetes mellitus (T2DM) development is unclear. We investigated associations between time-of-day-specific physical activity and incident T2DM, and whether theoretically reallocating activity from morning to later in the day was associated with changes in T2DM risk.</p><p><strong>Materials and methods: </strong>We included 4615 participants from The Maastricht Study cohort without diabetes (age 59.2 ± 8.6 years; 56.3% women). Device-based physical activity was measured over 7 days using activPAL monitors and classified into light-intensity physical activity (LPA) and moderate-to-vigorous intensity physical activity (MVPA), for morning (06:00-11:59 AM), afternoon (12:00-17:59 PM), evening (18:00-23:59 PM) and night (00:00-05:59 AM). Incident T2DM was assessed during a median 8.2-year follow-up. Cox proportional hazard and isotemporal substitution models were used, adjusted for sociodemographic and lifestyle factors, including diet, employment and sleep duration.</p><p><strong>Results: </strong>During follow-up, 168 participants (3.6%) developed T2DM. Each additional 10 min/day of afternoon LPA or MVPA was associated with lower T2DM risk (LPA: hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.70-0.97; MVPA: HR 0.85, 95% CI 0.72-1.00). Evening MVPA was also inversely associated with T2DM risk (0.65; 0.45-0.93), whereas night-time MVPA was associated with an increased risk (3.64; 1.30-10.17). No significant associations were found of morning LPA and MVPA or evening and night LPA with T2DM incidence. Substitution analyses indicated that reallocating 10 min of morning LPA to afternoon LPA (HR 0.71; 0.54-0.95) or morning MVPA to evening MVPA (HR: 0.64; 0.43-0.96) was associated with a lower T2DM risk, while no other significant associations were observed.</p><p><strong>Conclusions: </strong>Later-day physical activity, particularly in the afternoon, was associated with a lower incidence of T2DM, independent of intensity. This highlights the potential relevance of activity timing in relation to T2DM incidence.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145958239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Risk of recurrent diabetic ketoacidosis following initiation of sodium-glucose co-transporter 2 inhibitors in patients with an insulin-deficient diabetes and prior diabetic ketoacidosis: An observational cohort study. 胰岛素缺乏型糖尿病患者和既往糖尿病酮症酸中毒患者开始使用钠-葡萄糖共转运蛋白2抑制剂后复发性糖尿病酮症酸中毒的风险:一项观察性队列研究
IF 5.7 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-01-13 DOI: 10.1111/dom.70457
Anat Tsur, Omer Hamtzany, Rena Pollack, Avivit Cahn
{"title":"Risk of recurrent diabetic ketoacidosis following initiation of sodium-glucose co-transporter 2 inhibitors in patients with an insulin-deficient diabetes and prior diabetic ketoacidosis: An observational cohort study.","authors":"Anat Tsur, Omer Hamtzany, Rena Pollack, Avivit Cahn","doi":"10.1111/dom.70457","DOIUrl":"https://doi.org/10.1111/dom.70457","url":null,"abstract":"","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145958269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Prediction of heart failure as the first major cardiovascular disease event in type 2 diabetes 心衰作为2型糖尿病第一个主要心血管疾病事件的预测
IF 5.7 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-01-13 DOI: 10.1111/dom.70426
Julian W. Sacre PhD, Kristin Lundegard MSc, Kamel Mohammedi MD, Bendix Carstensen MSc, Hertzel C. Gerstein MD, Jonathan E. Shaw MD

Aims

Heart failure (HF) may develop in type 2 diabetes without prior cardiovascular disease (CVD). This study aimed to identify risk factors that distinguish CVD that presents first as a HF event versus CVD that presents first as an atherosclerotic event (ASCVD), among people with type 2 diabetes.

Materials and methods

ORIGIN and REWIND trial participants with type 2 diabetes but free of CVD (N = 6175; 64 ± 7 years, 50.1% female) were followed for ~5.8 years for incident CVD presenting first as either a HF event (HF hospitalization or HF death), ASCVD (myocardial infarction, unstable angina, stroke, or revascularization), or other cardiovascular death. Multi-state models characterised event-specific associations of risk factors with each possible first CVD event.

Results

HF was the first event in 16.8% of 1024 incident CVD cases. Older age, higher BMI, and higher urine albumin:creatinine ratio were more strongly associated with CVD manifesting first as HF, rather than as ASCVD or other cardiovascular death. ASCVD as the first event (65.2% of cases) was more strongly associated with worse LDL-cholesterol and HbA1c. These unique associations of risk factors with HF versus ASCVD translated to variable probabilities of HF as the first CVD event, depending on the clinical profile (32.0% for a profile enriched with HF-specific risk factors versus 5.1% for a profile enriched with ASCVD-specific risk factors).

Conclusions

CVD that presents first as a HF event is common in type 2 diabetes and its risk factors are distinct from those associated with CVD that presents first as an ASCVD event.

目的:心力衰竭(HF)可能发生在没有心血管疾病(CVD)的2型糖尿病患者。本研究旨在确定在2型糖尿病患者中区分首先表现为HF事件的CVD与首先表现为动脉粥样硬化事件(ASCVD)的CVD的危险因素。材料和方法:ORIGIN和REWIND试验参与者均为2型糖尿病,但无CVD (N = 6175; 64±7岁,50.1%为女性),随访约5.8年,CVD事件首先表现为HF事件(HF住院或HF死亡)、ASCVD(心肌梗死、不稳定心绞痛、中风或血管重建术)或其他心血管死亡。多状态模型描述了风险因素与每种可能的首次心血管疾病事件之间的事件特异性关联。结果:在1024例CVD病例中,16.8%的患者以HF为第一事件。年龄越大、BMI越高、尿白蛋白:肌酐比值越高与CVD的相关性越强,CVD首先表现为心衰,而不是ASCVD或其他心血管死亡。ASCVD作为第一事件(65.2%的病例)与较差的ldl -胆固醇和HbA1c有更强的相关性。这些危险因素与HF和ASCVD的独特关联转化为HF作为第一个CVD事件的可变概率,取决于临床概况(具有HF特异性危险因素的概况为32.0%,而具有ASCVD特异性危险因素的概况为5.1%)。结论:CVD首先表现为心衰事件在2型糖尿病中很常见,其危险因素与CVD首先表现为ASCVD事件的危险因素不同。
{"title":"Prediction of heart failure as the first major cardiovascular disease event in type 2 diabetes","authors":"Julian W. Sacre PhD,&nbsp;Kristin Lundegard MSc,&nbsp;Kamel Mohammedi MD,&nbsp;Bendix Carstensen MSc,&nbsp;Hertzel C. Gerstein MD,&nbsp;Jonathan E. Shaw MD","doi":"10.1111/dom.70426","DOIUrl":"10.1111/dom.70426","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Heart failure (HF) may develop in type 2 diabetes without prior cardiovascular disease (CVD). This study aimed to identify risk factors that distinguish CVD that presents first as a HF event versus CVD that presents first as an atherosclerotic event (ASCVD), among people with type 2 diabetes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and methods</h3>\u0000 \u0000 <p>ORIGIN and REWIND trial participants with type 2 diabetes but free of CVD (<i>N</i> = 6175; 64 ± 7 years, 50.1% female) were followed for ~5.8 years for incident CVD presenting first as either a HF event (HF hospitalization or HF death), ASCVD (myocardial infarction, unstable angina, stroke, or revascularization), or other cardiovascular death. Multi-state models characterised event-specific associations of risk factors with each possible first CVD event.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>HF was the first event in 16.8% of 1024 incident CVD cases. Older age, higher BMI, and higher urine albumin:creatinine ratio were more strongly associated with CVD manifesting first as HF, rather than as ASCVD or other cardiovascular death. ASCVD as the first event (65.2% of cases) was more strongly associated with worse LDL-cholesterol and HbA1c. These unique associations of risk factors with HF versus ASCVD translated to variable probabilities of HF as the first CVD event, depending on the clinical profile (32.0% for a profile enriched with HF-specific risk factors versus 5.1% for a profile enriched with ASCVD-specific risk factors).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>CVD that presents first as a HF event is common in type 2 diabetes and its risk factors are distinct from those associated with CVD that presents first as an ASCVD event.</p>\u0000 </section>\u0000 </div>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":"28 3","pages":"2308-2316"},"PeriodicalIF":5.7,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145958277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The depletion of serine beta-lactamase-like protein (LACTB) ameliorates metabolic dysfunction-associated steatotic liver disease by reducing ubiquitin-mediated degradation of carnitine palmitoyltransferase 2. 丝氨酸β -内酰胺酶样蛋白(LACTB)的缺失通过减少泛素介导的肉碱棕榈酰基转移酶2的降解来改善代谢功能障碍相关的脂肪变性肝病。
IF 5.7 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-01-13 DOI: 10.1111/dom.70483
Wujiang Shi, Xin Liu, Nan Wang, Qianwen Zhang, Jianjun Gao, Canghai Guan, Yapeng Li, Chengru Yang, Shaowu Bi, Xinlei Zou, Xiangyu Zhong

Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) represents one of the most common chronic liver disorders worldwide, and its incidence continues to rise each year. Serine β-lactamase-like protein (LACTB) is a serine protease that plays a crucial role in lipid metabolism and hepatocellular carcinoma, but its function in MASLD remains unclear. Therefore, the study aims to elucidate the effect and mechanism of LACTB in the progression of MASLD.

Materials and methods: The expression of LACTB in liver tissues from MASLD patients and high-fat diet (HFD) fed mice was assessed. Both in vivo and in vitro models were established to examine the role and molecular mechanisms of LACTB in MASLD.

Results: LACTB protein levels were upregulated in the liver tissues from MASLD patients and HFD-fed mice. LACTB overexpression exacerbated hepatic steatosis, insulin resistance, and inflammation in HFD-fed mice. Conversely, LACTB knockdown improved these phenotypes. Mechanistically, LACTB interacted with CPT2 and promoted its ubiquitin-mediated degradation. The effect of LACTB in hepatocellular lipid metabolism was dependent on CPT2.

Conclusions: Our findings indicate that LACTB is a novel regulatory factor in MASLD by influencing the ubiquitin-mediated degradation of CPT2 to participate in disease progression. These findings may provide a novel potential therapeutic strategy for MASLD.

目的:代谢功能障碍相关脂肪变性肝病(MASLD)是世界范围内最常见的慢性肝脏疾病之一,其发病率每年都在持续上升。丝氨酸β-内酰胺酶样蛋白(LACTB)是一种丝氨酸蛋白酶,在脂质代谢和肝细胞癌中起着至关重要的作用,但其在MASLD中的功能尚不清楚。因此,本研究旨在阐明LACTB在MASLD进展中的作用和机制。材料与方法:测定MASLD患者和高脂饮食小鼠肝组织中乳酸脱氢酶(LACTB)的表达。我们建立了体内和体外模型,研究了LACTB在MASLD中的作用和分子机制。结果:MASLD患者和饲喂hfd的小鼠肝组织中乳酸泌乳蛋白水平上调。在饲喂hfd的小鼠中,LACTB过表达加重了肝脏脂肪变性、胰岛素抵抗和炎症。相反,敲低LACTB可改善这些表型。在机制上,LACTB与CPT2相互作用并促进其泛素介导的降解。LACTB对肝细胞脂质代谢的影响依赖于CPT2。结论:我们的研究结果表明,LACTB是MASLD中一种新的调控因子,通过影响泛素介导的CPT2降解参与疾病进展。这些发现可能为MASLD提供一种新的潜在治疗策略。
{"title":"The depletion of serine beta-lactamase-like protein (LACTB) ameliorates metabolic dysfunction-associated steatotic liver disease by reducing ubiquitin-mediated degradation of carnitine palmitoyltransferase 2.","authors":"Wujiang Shi, Xin Liu, Nan Wang, Qianwen Zhang, Jianjun Gao, Canghai Guan, Yapeng Li, Chengru Yang, Shaowu Bi, Xinlei Zou, Xiangyu Zhong","doi":"10.1111/dom.70483","DOIUrl":"https://doi.org/10.1111/dom.70483","url":null,"abstract":"<p><strong>Aims: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) represents one of the most common chronic liver disorders worldwide, and its incidence continues to rise each year. Serine β-lactamase-like protein (LACTB) is a serine protease that plays a crucial role in lipid metabolism and hepatocellular carcinoma, but its function in MASLD remains unclear. Therefore, the study aims to elucidate the effect and mechanism of LACTB in the progression of MASLD.</p><p><strong>Materials and methods: </strong>The expression of LACTB in liver tissues from MASLD patients and high-fat diet (HFD) fed mice was assessed. Both in vivo and in vitro models were established to examine the role and molecular mechanisms of LACTB in MASLD.</p><p><strong>Results: </strong>LACTB protein levels were upregulated in the liver tissues from MASLD patients and HFD-fed mice. LACTB overexpression exacerbated hepatic steatosis, insulin resistance, and inflammation in HFD-fed mice. Conversely, LACTB knockdown improved these phenotypes. Mechanistically, LACTB interacted with CPT2 and promoted its ubiquitin-mediated degradation. The effect of LACTB in hepatocellular lipid metabolism was dependent on CPT2.</p><p><strong>Conclusions: </strong>Our findings indicate that LACTB is a novel regulatory factor in MASLD by influencing the ubiquitin-mediated degradation of CPT2 to participate in disease progression. These findings may provide a novel potential therapeutic strategy for MASLD.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145958293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Incremental value of DXA-derived fat distribution over anthropometrics for classifying metabolically unhealthy obesity: A population-based analysis. dxa衍生脂肪分布的增量价值优于人体测量学对代谢不健康肥胖的分类:基于人群的分析。
IF 5.7 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-01-13 DOI: 10.1111/dom.70479
Shaun Khanna, Nelson Wang, Aditya Bhat, Clare Arnott, Nitesh Nerlekar
{"title":"Incremental value of DXA-derived fat distribution over anthropometrics for classifying metabolically unhealthy obesity: A population-based analysis.","authors":"Shaun Khanna, Nelson Wang, Aditya Bhat, Clare Arnott, Nitesh Nerlekar","doi":"10.1111/dom.70479","DOIUrl":"https://doi.org/10.1111/dom.70479","url":null,"abstract":"","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145958234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comparative prognostic value of nine cardiorenal biomarkers for mortality among adults with prediabetes and diabetes. 九种心肾生物标志物对糖尿病前期和糖尿病成人死亡率的预后价值比较
IF 5.7 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-01-13 DOI: 10.1111/dom.70470
Chunyan Chai, Shasha Chen, Gongchang Guan, Qianwei Cui, Xu Zhu, Rutai Hui, Shenglin He, Zhao Zhao, Hui Pang, Ling Zhu

Background: Cardiorenal biomarkers are increasingly recognized as valuable tools for risk stratification in individuals with dysglycemia. However, their comparative prognostic value for long-term all-cause and cardio-cerebrovascular disease (CCD) mortality remains unclear.

Methods: We analyzed data from 4087 adults with prediabetes or diabetes from NHANES 1999-2004, with mortality follow-up through 2019. Nine biomarkers were assessed: NT-proBNP, hs-cTnT, hs-cTnI, CRP, UACR, BUN/Cr ratio, uric acid, cystatin C, and β2-microglobulin. Survey-weighted Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and CCD mortality. Time-dependent receiver operating characteristic (ROC) analysis evaluated discriminative performance. Weighted quantile sum (WQS) regression was applied to assess the collective impact of biomarkers.

Results: During a median follow-up of 16.5 years, 1855 all-cause deaths and 630 CCD deaths were recorded. In fully adjusted models, NT-proBNP (HR = 2.19; 95% CI, 1.73-2.78), hs-cTnT (HR = 2.30; 1.63-3.24), hs-cTnI (HR = 1.80; 1.44-2.24), cystatin C (HR = 1.76; 1.36-2.28), β2-microglobulin (HR = 1.72; 1.36-2.16), and UACR (HR = 1.50; 1.23-1.81) were significantly associated with all-cause mortality, with similar findings for CCD mortality. NT-proBNP and hs-cTnT demonstrated the strongest discrimination for 10-year all-cause (AUCs: 0.80 and 0.81) and CCD mortality (AUCs: both 0.85). Adding NT-proBNP or hs-cTnT to the base model significantly improved predictive accuracy. WQS regression confirmed a significant positive association with all-cause (HR = 1.56; 95% CI, 1.32-1.84) and CCD mortality (HR = 1.39; 95% CI, 1.14-1.70), with NT-proBNP, hs-cTnT, and cystatin C contributing most strongly.

Conclusions: Among nine evaluated cardiorenal biomarkers, NT-proBNP, hs-cTnT, and cystatin C demonstrated the strongest and most consistent associations with all-cause and CCD mortality among adults with prediabetes and diabetes, as well as the highest incremental predictive value. These biomarkers may serve as key components in future risk stratification models for individuals with prediabetes or diabetes.

背景:心肾生物标志物越来越被认为是血糖异常个体风险分层的有价值工具。然而,它们对长期全因和心脑血管疾病(CCD)死亡率的比较预后价值尚不清楚。方法:我们分析了1999-2004年NHANES中4087名糖尿病前期或糖尿病成年人的数据,并对死亡率进行了随访至2019年。评估9项生物标志物:NT-proBNP、hs-cTnT、hs-cTnI、CRP、UACR、BUN/Cr比值、尿酸、胱抑素C和β2微球蛋白。使用调查加权Cox比例风险模型来估计全因死亡率和CCD死亡率的风险比(hr)和95%置信区间(ci)。时间相关的受试者工作特征(ROC)分析评估了鉴别性能。加权分位数和(WQS)回归用于评估生物标志物的集体影响。结果:在16.5年的中位随访期间,记录了1855例全因死亡和630例CCD死亡。在完全调整的模型中,NT-proBNP (HR = 2.19; 95% CI, 1.73-2.78)、hs-cTnT (HR = 2.30; 1.63-3.24)、hs-cTnI (HR = 1.80; 1.44-2.24)、胱氨酸抑制素C (HR = 1.76; 1.36-2.28)、β2-微球蛋白(HR = 1.72; 1.36-2.16)和UACR (HR = 1.50; 1.23-1.81)与全因死亡率显著相关,与CCD死亡率的结果相似。NT-proBNP和hs-cTnT在10年全因死亡率(auc分别为0.80和0.81)和CCD死亡率(auc均为0.85)上表现出最强的区别。在基础模型中加入NT-proBNP或hs-cTnT可显著提高预测精度。WQS回归证实了与全因(HR = 1.56; 95% CI, 1.32-1.84)和CCD死亡率(HR = 1.39; 95% CI, 1.14-1.70)的显著正相关,其中NT-proBNP、hs-cTnT和胱抑素C贡献最大。结论:在9个评估的心肾生物标志物中,NT-proBNP、hs-cTnT和胱抑制素C与糖尿病前期和糖尿病成人的全因死亡率和CCD死亡率的相关性最强、最一致,并且具有最高的增量预测值。这些生物标志物可以作为未来糖尿病前期或糖尿病患者风险分层模型的关键组成部分。
{"title":"Comparative prognostic value of nine cardiorenal biomarkers for mortality among adults with prediabetes and diabetes.","authors":"Chunyan Chai, Shasha Chen, Gongchang Guan, Qianwei Cui, Xu Zhu, Rutai Hui, Shenglin He, Zhao Zhao, Hui Pang, Ling Zhu","doi":"10.1111/dom.70470","DOIUrl":"https://doi.org/10.1111/dom.70470","url":null,"abstract":"<p><strong>Background: </strong>Cardiorenal biomarkers are increasingly recognized as valuable tools for risk stratification in individuals with dysglycemia. However, their comparative prognostic value for long-term all-cause and cardio-cerebrovascular disease (CCD) mortality remains unclear.</p><p><strong>Methods: </strong>We analyzed data from 4087 adults with prediabetes or diabetes from NHANES 1999-2004, with mortality follow-up through 2019. Nine biomarkers were assessed: NT-proBNP, hs-cTnT, hs-cTnI, CRP, UACR, BUN/Cr ratio, uric acid, cystatin C, and β2-microglobulin. Survey-weighted Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and CCD mortality. Time-dependent receiver operating characteristic (ROC) analysis evaluated discriminative performance. Weighted quantile sum (WQS) regression was applied to assess the collective impact of biomarkers.</p><p><strong>Results: </strong>During a median follow-up of 16.5 years, 1855 all-cause deaths and 630 CCD deaths were recorded. In fully adjusted models, NT-proBNP (HR = 2.19; 95% CI, 1.73-2.78), hs-cTnT (HR = 2.30; 1.63-3.24), hs-cTnI (HR = 1.80; 1.44-2.24), cystatin C (HR = 1.76; 1.36-2.28), β2-microglobulin (HR = 1.72; 1.36-2.16), and UACR (HR = 1.50; 1.23-1.81) were significantly associated with all-cause mortality, with similar findings for CCD mortality. NT-proBNP and hs-cTnT demonstrated the strongest discrimination for 10-year all-cause (AUCs: 0.80 and 0.81) and CCD mortality (AUCs: both 0.85). Adding NT-proBNP or hs-cTnT to the base model significantly improved predictive accuracy. WQS regression confirmed a significant positive association with all-cause (HR = 1.56; 95% CI, 1.32-1.84) and CCD mortality (HR = 1.39; 95% CI, 1.14-1.70), with NT-proBNP, hs-cTnT, and cystatin C contributing most strongly.</p><p><strong>Conclusions: </strong>Among nine evaluated cardiorenal biomarkers, NT-proBNP, hs-cTnT, and cystatin C demonstrated the strongest and most consistent associations with all-cause and CCD mortality among adults with prediabetes and diabetes, as well as the highest incremental predictive value. These biomarkers may serve as key components in future risk stratification models for individuals with prediabetes or diabetes.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145958298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Change in body mass index and disease burden among people with obesity and multiple long-term conditions. 肥胖和多种长期疾病患者的体重指数变化和疾病负担
IF 5.7 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-01-12 DOI: 10.1111/dom.70446
Kamlesh Khunti, Alex Mourer, Silvia Capucci, Lua Wilkinson, Klaus K Andersen, Abd A Tahrani, Camilla S Morgen

Aims: Obesity is a risk factor for multiple long-term conditions (MLTCs/multimorbidity). However, the impact of weight loss in people with MLTCs is unclear. We investigated the association between body mass index (BMI) change and the development of obesity-related complications (ORCs), as well as clinical and economic outcomes in individuals with obesity and MLTCs.

Materials and methods: This cohort study included adults aged ≤70 years with BMI ≥30 kg/m2 and ≥2 ORCs. BMI was recorded during Years 1 and 4 of the baseline period. BMI change was categorised as increases or decreases of 3%-7%, 7%-15% and 15%-30%. Data were analysed using Cox regression (hazard ratios [HRs] for mental-health conditions, hospitalisation and mortality) and Ghosh-Lin models (risk of ≥1 new ORC and clinical consultations).

Results: A total of 618 426 individuals were included. The mean number of ORCs at index (Year 4) was 3.8 (standard deviation 1.5). HRs (95% confidence intervals) for incident ORCs were 0.96 (0.94-0.98), 0.98 (0.96-0.99) and 0.98 (0.97-0.99) for the highest to lowest BMI reductions, respectively; BMI increases were associated with HRs >1.00. Risk ratios for consultations were 0.99 (0.98-1.00), 0.99 (0.98-1.00) and 1.00 (0.99-1.00). BMI reductions were linked to lower polypharmacy rates. Both BMI decrease and increase were associated with higher HRs for mental-health conditions, hospitalisation and mortality versus stable BMI.

Conclusions: Weight loss in individuals with obesity and MLTCs was linked to both favourable and adverse outcomes, highlighting the importance of personalised treatment approaches that consider outcomes beyond weight loss.

目的:肥胖是多种长期疾病(MLTCs/多病)的危险因素。然而,减肥对MLTCs患者的影响尚不清楚。我们调查了体重指数(BMI)变化与肥胖相关并发症(ORCs)发展之间的关系,以及肥胖和MLTCs患者的临床和经济结果。材料和方法:本队列研究纳入年龄≤70岁、BMI≥30 kg/m2、ORCs≥2的成年人。在基线期的第1年和第4年记录BMI。BMI变化分为增加或减少3%-7%、7%-15%和15%-30%。使用Cox回归(精神健康状况、住院和死亡率的风险比[hr])和Ghosh-Lin模型(≥1个新的ORC风险和临床咨询)对数据进行分析。结果:共纳入618 426人。指数(第4年)的平均orc数为3.8(标准差为1.5)。BMI降低最高至最低的orc事件的hr(95%可信区间)分别为0.96(0.94-0.98)、0.98(0.96-0.99)和0.98 (0.97-0.99);BMI升高与hr升高相关。就诊风险比分别为0.99(0.98-1.00)、0.99(0.98-1.00)和1.00(0.99-1.00)。BMI的降低与较低的多药率有关。与BMI稳定的人相比,BMI的下降和增加都与精神健康状况、住院和死亡率的高hr相关。结论:肥胖和MLTCs患者的体重减轻与有利和不利的结果相关,强调了考虑体重减轻以外的结果的个性化治疗方法的重要性。
{"title":"Change in body mass index and disease burden among people with obesity and multiple long-term conditions.","authors":"Kamlesh Khunti, Alex Mourer, Silvia Capucci, Lua Wilkinson, Klaus K Andersen, Abd A Tahrani, Camilla S Morgen","doi":"10.1111/dom.70446","DOIUrl":"https://doi.org/10.1111/dom.70446","url":null,"abstract":"<p><strong>Aims: </strong>Obesity is a risk factor for multiple long-term conditions (MLTCs/multimorbidity). However, the impact of weight loss in people with MLTCs is unclear. We investigated the association between body mass index (BMI) change and the development of obesity-related complications (ORCs), as well as clinical and economic outcomes in individuals with obesity and MLTCs.</p><p><strong>Materials and methods: </strong>This cohort study included adults aged ≤70 years with BMI ≥30 kg/m<sup>2</sup> and ≥2 ORCs. BMI was recorded during Years 1 and 4 of the baseline period. BMI change was categorised as increases or decreases of 3%-7%, 7%-15% and 15%-30%. Data were analysed using Cox regression (hazard ratios [HRs] for mental-health conditions, hospitalisation and mortality) and Ghosh-Lin models (risk of ≥1 new ORC and clinical consultations).</p><p><strong>Results: </strong>A total of 618 426 individuals were included. The mean number of ORCs at index (Year 4) was 3.8 (standard deviation 1.5). HRs (95% confidence intervals) for incident ORCs were 0.96 (0.94-0.98), 0.98 (0.96-0.99) and 0.98 (0.97-0.99) for the highest to lowest BMI reductions, respectively; BMI increases were associated with HRs >1.00. Risk ratios for consultations were 0.99 (0.98-1.00), 0.99 (0.98-1.00) and 1.00 (0.99-1.00). BMI reductions were linked to lower polypharmacy rates. Both BMI decrease and increase were associated with higher HRs for mental-health conditions, hospitalisation and mortality versus stable BMI.</p><p><strong>Conclusions: </strong>Weight loss in individuals with obesity and MLTCs was linked to both favourable and adverse outcomes, highlighting the importance of personalised treatment approaches that consider outcomes beyond weight loss.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145958241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Changes in how people living with obesity perceive weight-related discussions with their healthcare professional: Results from the cross-sectional online ACTION-DK 2022 and 2024 studies. 肥胖人群对与其医疗保健专业人员进行体重相关讨论的看法的变化:来自横截面在线行动- dk 2022和2024研究的结果
IF 5.7 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-01-12 DOI: 10.1111/dom.70474
Mette Bøgelund, Amanda F Rasmussen, Pernille Andreassen, Per Nielsen, Signe Stensen, Jens M Bruun

Aims: This study investigated changes in how people living with obesity (PwO) perceive weight-related discussions with healthcare professionals (HCPs) in Denmark from 2022 to 2024, a period marked by shifts in obesity treatment options as well as the broader understanding of obesity.

Materials and methods: A cross-sectional online survey was conducted among adult PwO in Denmark, building on the 2022 Awareness, Care, and Treatment In Obesity maNagement-Denmark survey with a few modifications. Data were collected via representative online panels from September to October 2024. Adjusted logistic regression models were performed.

Results: A total of 1005 PwO participated in the 2024 survey, compared to 879 in the 2022 survey. The proportion of PwO discussing weight with HCPs increased significantly from 38% in 2022 to 58% in 2024. The percentage of PwO reporting positive feelings after weight consultations did not change significantly. PwO in 2024 still refrained from discussing weight due to fear of prejudice (23%), previous negative experiences (17%) and the belief that reducing weight was their own responsibility (46%). Subgroup analyses in 2024 revealed that those currently using weight loss medications reported the most positive perceptions of weight-related discussions with their HCP.

Conclusions: Overall increased engagement of PwO regarding weight-related discussions with HCPs was observed from 2022 to 2024. However, barriers persist, since some PwO avoid interactions with HCPs due to previous experiences with stigma or the fear of being judged. Continued efforts are essential to address these barriers, enhance HCP education about weight-related bias, and foster a supportive environment for PwO in healthcare settings.

目的:本研究调查了2022年至2024年丹麦肥胖患者(pvo)对与医疗保健专业人员(HCPs)进行体重相关讨论的看法的变化,这一时期以肥胖治疗选择的转变以及对肥胖的更广泛理解为标志。材料和方法:在丹麦2022年肥胖管理的意识、护理和治疗调查的基础上,对丹麦成年ppo进行了横断面在线调查,并进行了一些修改。从2024年9月到10月,通过有代表性的在线小组收集数据。采用调整后的logistic回归模型。结果:2024年共有1005名ppo参与调查,而2022年共有879名ppo参与调查。pvo与HCPs讨论权重的比例从2022年的38%显著增加到2024年的58%。在体重咨询后报告积极感觉的ppo百分比没有显着变化。2024年的女性仍然因为害怕偏见(23%)、之前的负面经历(17%)和认为减肥是自己的责任(46%)而避免讨论体重。2024年的亚组分析显示,那些目前正在使用减肥药的人报告了与他们的HCP进行体重相关讨论的最积极的看法。结论:从2022年到2024年,观察到ppo在与hcp进行体重相关讨论时的总体参与度有所增加。然而,障碍仍然存在,因为一些残疾人由于以前的耻辱经历或害怕被评判而避免与卫生保健提供者互动。必须继续努力解决这些障碍,加强关于体重相关偏见的HCP教育,并在医疗保健环境中为ppo营造一个支持性环境。
{"title":"Changes in how people living with obesity perceive weight-related discussions with their healthcare professional: Results from the cross-sectional online ACTION-DK 2022 and 2024 studies.","authors":"Mette Bøgelund, Amanda F Rasmussen, Pernille Andreassen, Per Nielsen, Signe Stensen, Jens M Bruun","doi":"10.1111/dom.70474","DOIUrl":"https://doi.org/10.1111/dom.70474","url":null,"abstract":"<p><strong>Aims: </strong>This study investigated changes in how people living with obesity (PwO) perceive weight-related discussions with healthcare professionals (HCPs) in Denmark from 2022 to 2024, a period marked by shifts in obesity treatment options as well as the broader understanding of obesity.</p><p><strong>Materials and methods: </strong>A cross-sectional online survey was conducted among adult PwO in Denmark, building on the 2022 Awareness, Care, and Treatment In Obesity maNagement-Denmark survey with a few modifications. Data were collected via representative online panels from September to October 2024. Adjusted logistic regression models were performed.</p><p><strong>Results: </strong>A total of 1005 PwO participated in the 2024 survey, compared to 879 in the 2022 survey. The proportion of PwO discussing weight with HCPs increased significantly from 38% in 2022 to 58% in 2024. The percentage of PwO reporting positive feelings after weight consultations did not change significantly. PwO in 2024 still refrained from discussing weight due to fear of prejudice (23%), previous negative experiences (17%) and the belief that reducing weight was their own responsibility (46%). Subgroup analyses in 2024 revealed that those currently using weight loss medications reported the most positive perceptions of weight-related discussions with their HCP.</p><p><strong>Conclusions: </strong>Overall increased engagement of PwO regarding weight-related discussions with HCPs was observed from 2022 to 2024. However, barriers persist, since some PwO avoid interactions with HCPs due to previous experiences with stigma or the fear of being judged. Continued efforts are essential to address these barriers, enhance HCP education about weight-related bias, and foster a supportive environment for PwO in healthcare settings.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145958243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pharmacokinetics and safety of HR17031, a fixed-ratio of INS068/Noiiglutide combination, in Chinese patients with hepatic impairment. HR17031 (INS068/诺依鲁肽固定比例联合用药)在中国肝功能损害患者中的药代动力学及安全性
IF 5.7 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-01-12 DOI: 10.1111/dom.70450
Di Wang, Xuehu Gao, Jiajia Mai, Hong Zhang, Hongda Lin, Yanhua Ding, Lei Diao

Aims: To evaluate the pharmacokinetics (PK) and safety of HR17031 (a fixed-ratio combination of INS068 and Noiiglutide) in subjects with hepatic impairment.

Materials and methods: This open-label, single-dose, nonrandomised, parallel-design trial enrolled 24 subjects with mild (Child-Pugh A), moderate (Child-Pugh B) and normal hepatic function (n = 8 each). Participants received a single subcutaneous injection of HR17031 (10 U/0.024 mg). PK parameters of INS068 and Noiiglutide were determined by liquid chromatography-tandem mass spectrometry, free drug fractions were assessed by ultracentrifugation, and serum C-peptide concentrations were measured. Safety was monitored throughout.

Results: PK profiles of INS068 and Noiiglutide in subjects with mild hepatic impairment were comparable to those with normal function, while modest reductions were observed in moderate impairment (INS068 AUC0-∞ geometric mean ratio [GMR]: 0.814 [0.703-0.944]; Noiiglutide AUC0-∞ GMR: 0.713 [0.574-0.886]). Unbound fractions of both components and C-peptide concentrations showed no significant differences across groups. HR17031 was well tolerated, and there were no serious adverse events.

Conclusions: HR17031 demonstrated PK profiles of INS068 and Noiiglutide comparable between subjects with mild or moderate hepatic impairment and those with normal hepatic function, with modest reductions in moderate impairment. The treatment was well tolerated with a favourable safety profile, and no significant differences in C-peptide concentrations were observed across groups.

目的:评价HR17031 (INS068与诺依鲁肽的固定比例组合)在肝功能损害患者中的药代动力学(PK)和安全性。材料和方法:这项开放标签、单剂量、非随机、平行设计的试验纳入了24例肝功能轻度(Child-Pugh A)、中度(Child-Pugh B)和正常的受试者(各8例)。参与者接受单次皮下注射HR17031 (10 U/0.024 mg)。采用液相色谱-串联质谱法测定INS068和Noiiglutide的PK参数,采用超离心法测定游离药物组分,测定血清c肽浓度。安全受到全程监控。结果:轻度肝功能损害受试者中INS068和Noiiglutide的PK谱与功能正常者相当,中度肝功能损害受试者中INS068 AUC0-∞几何平均比[GMR]: 0.814 [0.703-0.944]; Noiiglutide AUC0-∞GMR: 0.713[0.574-0.886])。各组间未结合组分和c肽浓度无显著差异。HR17031耐受性良好,无严重不良事件。结论:HR17031显示,在轻度或中度肝功能损害受试者和肝功能正常受试者中,INS068和诺依鲁肽的PK谱具有可比性,中度肝功能损害患者的PK谱略有下降。治疗耐受性良好,安全性良好,各组间c肽浓度无显著差异。
{"title":"Pharmacokinetics and safety of HR17031, a fixed-ratio of INS068/Noiiglutide combination, in Chinese patients with hepatic impairment.","authors":"Di Wang, Xuehu Gao, Jiajia Mai, Hong Zhang, Hongda Lin, Yanhua Ding, Lei Diao","doi":"10.1111/dom.70450","DOIUrl":"https://doi.org/10.1111/dom.70450","url":null,"abstract":"<p><strong>Aims: </strong>To evaluate the pharmacokinetics (PK) and safety of HR17031 (a fixed-ratio combination of INS068 and Noiiglutide) in subjects with hepatic impairment.</p><p><strong>Materials and methods: </strong>This open-label, single-dose, nonrandomised, parallel-design trial enrolled 24 subjects with mild (Child-Pugh A), moderate (Child-Pugh B) and normal hepatic function (n = 8 each). Participants received a single subcutaneous injection of HR17031 (10 U/0.024 mg). PK parameters of INS068 and Noiiglutide were determined by liquid chromatography-tandem mass spectrometry, free drug fractions were assessed by ultracentrifugation, and serum C-peptide concentrations were measured. Safety was monitored throughout.</p><p><strong>Results: </strong>PK profiles of INS068 and Noiiglutide in subjects with mild hepatic impairment were comparable to those with normal function, while modest reductions were observed in moderate impairment (INS068 AUC<sub>0-∞</sub> geometric mean ratio [GMR]: 0.814 [0.703-0.944]; Noiiglutide AUC<sub>0-∞</sub> GMR: 0.713 [0.574-0.886]). Unbound fractions of both components and C-peptide concentrations showed no significant differences across groups. HR17031 was well tolerated, and there were no serious adverse events.</p><p><strong>Conclusions: </strong>HR17031 demonstrated PK profiles of INS068 and Noiiglutide comparable between subjects with mild or moderate hepatic impairment and those with normal hepatic function, with modest reductions in moderate impairment. The treatment was well tolerated with a favourable safety profile, and no significant differences in C-peptide concentrations were observed across groups.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145958279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Diabetes, Obesity & Metabolism
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1