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.
{"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}
{"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}
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.
{"title":"Prediction of heart failure as the first major cardiovascular disease event in type 2 diabetes","authors":"Julian W. Sacre PhD, Kristin Lundegard MSc, Kamel Mohammedi MD, Bendix Carstensen MSc, Hertzel C. Gerstein MD, 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}
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.
{"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}
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}
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.
{"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}
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.
{"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}
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.
{"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}
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.
{"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}
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