Pub Date : 2025-01-27DOI: 10.1016/s2213-8587(24)00374-7
David N O'Neal, Glynis P Ross
No Abstract
{"title":"Automated insulin delivery postpartum: insights from the AiDAPT study extension","authors":"David N O'Neal, Glynis P Ross","doi":"10.1016/s2213-8587(24)00374-7","DOIUrl":"https://doi.org/10.1016/s2213-8587(24)00374-7","url":null,"abstract":"No Abstract","PeriodicalId":48790,"journal":{"name":"The Lancet Diabetes & Endocrinology","volume":"25 1","pages":""},"PeriodicalIF":44.5,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143050775","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}
Pub Date : 2025-01-27DOI: 10.1016/s2213-8587(24)00340-1
Tara T M Lee, Corinne Collett, Simon Bergford, Sara Hartnell, Eleanor M Scott, Robert S Lindsay, Katharine F Hunt, David R McCance, Rebecca M Reynolds, Malgorzata E Wilinska, Judy Sibayan, Craig Kollman, Roman Hovorka, Helen R Murphy
<h3>Background</h3>Clinical guidelines in the UK and elsewhere do not specifically address hybrid closed loop (HCL) use in the postpartum period when the demands of caring for a newborn are paramount. Our aim was to evaluate the safety and efficacy of HCL use during the first 6 months postpartum compared with standard care.<h3>Methods</h3>In this prespecified extension to a multicentre, randomised controlled trial, pregnant women with type 1 diabetes at nine UK sites were followed up for 6 months postpartum. Eligible participants (AiDAPT participants recruited after the implementation of the postpartum protocol amendment approval, those still pregnant or within six months of delivery at the time of amendment implementation and still using HCL or continuous glucose monitoring [CGM] therapy) continued their randomly assigned treatment, either standard insulin therapy with CGM or HCL therapy (CamAPS FX system version 0.3.1, CamDiab, Cambridge, UK). Participants were randomised in a 1:1 ratio with stratification by clinical site using randomly permuted block sizes of 2 or 4. The primary outcome was the between-group difference in percentage time in range ([TIR] 3·9–10·0 mmol/L [70–180mg/dL]), measured during the periods of month 0 up to 3, months 3 to 6, and over 6 months postpartum. The study is registered at <span><span>ClinicalTrials.gov</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span> (ISRCTN56898625) and is complete.<h3>Findings</h3>Of the 124 AiDAPT trial participants, 66 (53%) were ineligible for inclusion in the postpartum extension, and 57 participants consented to continue their treatment per original random allocation. The mean age was 31 years (SD 4), and all participants had early pregnancy HbA<sub>1c</sub> 59·4 mmol/mol (SD 10·5 [7·6% SD 1·0%]). In the 6 months postpartum, mean time with glucose levels within the target range was higher in the HCL group compared with the standard care group (72% [SD 12%] <em>vs</em> 54% [17%]), with an adjusted treatment difference of 15% (95% CI 7 to 22). Results for hyperglycaemia (>10·0 mmol/L) and mean CGM glucose also favoured HCL (–14% [95% CI –23% to –6%] and –1·3 mmol/L [–2·3 to –0·3], respectively). Hypoglycaemia rates were low, with no between-group differences (2·4% <em>vs</em> 2·6%). There were no treatment effect changes depending on postpartum period (0 up to 3 months <em>vs</em> 3 to 6 months) and no unanticipated safety problems.<h3>Interpretation</h3>Participants in the HCL group maintained 70% TIR during the first 6 months postpartum, supporting continued use of HCL rather than standard insulin therapy for people with diabetes once they have given birth.<h3>Funding</h3>National Institute for Health Research, Juvenile Diabetes Research Foundation, and Diabetes Research & Wellness Foundation. CGM devices were provided by
{"title":"Automated insulin delivery during the first 6 months postpartum (AiDAPT): a prespecified extension study","authors":"Tara T M Lee, Corinne Collett, Simon Bergford, Sara Hartnell, Eleanor M Scott, Robert S Lindsay, Katharine F Hunt, David R McCance, Rebecca M Reynolds, Malgorzata E Wilinska, Judy Sibayan, Craig Kollman, Roman Hovorka, Helen R Murphy","doi":"10.1016/s2213-8587(24)00340-1","DOIUrl":"https://doi.org/10.1016/s2213-8587(24)00340-1","url":null,"abstract":"<h3>Background</h3>Clinical guidelines in the UK and elsewhere do not specifically address hybrid closed loop (HCL) use in the postpartum period when the demands of caring for a newborn are paramount. Our aim was to evaluate the safety and efficacy of HCL use during the first 6 months postpartum compared with standard care.<h3>Methods</h3>In this prespecified extension to a multicentre, randomised controlled trial, pregnant women with type 1 diabetes at nine UK sites were followed up for 6 months postpartum. Eligible participants (AiDAPT participants recruited after the implementation of the postpartum protocol amendment approval, those still pregnant or within six months of delivery at the time of amendment implementation and still using HCL or continuous glucose monitoring [CGM] therapy) continued their randomly assigned treatment, either standard insulin therapy with CGM or HCL therapy (CamAPS FX system version 0.3.1, CamDiab, Cambridge, UK). Participants were randomised in a 1:1 ratio with stratification by clinical site using randomly permuted block sizes of 2 or 4. The primary outcome was the between-group difference in percentage time in range ([TIR] 3·9–10·0 mmol/L [70–180mg/dL]), measured during the periods of month 0 up to 3, months 3 to 6, and over 6 months postpartum. The study is registered at <span><span>ClinicalTrials.gov</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span> (ISRCTN56898625) and is complete.<h3>Findings</h3>Of the 124 AiDAPT trial participants, 66 (53%) were ineligible for inclusion in the postpartum extension, and 57 participants consented to continue their treatment per original random allocation. The mean age was 31 years (SD 4), and all participants had early pregnancy HbA<sub>1c</sub> 59·4 mmol/mol (SD 10·5 [7·6% SD 1·0%]). In the 6 months postpartum, mean time with glucose levels within the target range was higher in the HCL group compared with the standard care group (72% [SD 12%] <em>vs</em> 54% [17%]), with an adjusted treatment difference of 15% (95% CI 7 to 22). Results for hyperglycaemia (>10·0 mmol/L) and mean CGM glucose also favoured HCL (–14% [95% CI –23% to –6%] and –1·3 mmol/L [–2·3 to –0·3], respectively). Hypoglycaemia rates were low, with no between-group differences (2·4% <em>vs</em> 2·6%). There were no treatment effect changes depending on postpartum period (0 up to 3 months <em>vs</em> 3 to 6 months) and no unanticipated safety problems.<h3>Interpretation</h3>Participants in the HCL group maintained 70% TIR during the first 6 months postpartum, supporting continued use of HCL rather than standard insulin therapy for people with diabetes once they have given birth.<h3>Funding</h3>National Institute for Health Research, Juvenile Diabetes Research Foundation, and Diabetes Research & Wellness Foundation. CGM devices were provided by","PeriodicalId":48790,"journal":{"name":"The Lancet Diabetes & Endocrinology","volume":"117 1","pages":""},"PeriodicalIF":44.5,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143050776","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}
Pub Date : 2025-01-24DOI: 10.1016/s2213-8587(24)00363-2
Naveed Sattar, Matthew M Y Lee
The extent to which newer, incretin-based drugs for obesity improve disease outcomes via weight loss versus the direct effects of these drugs is the subject of intense interest. Although reductions in major adverse cardiovascular events appear to be predominantly driven by the direct tissue effects of such drugs, the associated weight loss effects must be relevant to the benefits observed in other major outcomes, albeit to differing extents. In this Personal View, we draw on evidence to support that weight loss is at least partly responsible (albeit to differing extents) for the reported benefits of incretin-based drugs for obesity in people living with heart failure with preserved ejection fraction, hypertension, chronic kidney disease, and type 2 diabetes. Concurrently, we propose that drug-induced weight loss is largely responsible for the reported improvements in osteoarthritis, obstructive sleep apnoea, and metabolic dysfunction-associated steatohepatitis outcomes. However, more evidence is needed to solidify these observations, including, when possible, trials comparing the effects of incretin-based drugs for obesity with calorie-reduced diets on both outcomes and mechanistic pathways. Such evidence has implications for public health and the design of future trials of novel drugs for obesity.
{"title":"Estimating direct tissue effects versus weight loss effects of incretin-based drugs for obesity on various chronic conditions","authors":"Naveed Sattar, Matthew M Y Lee","doi":"10.1016/s2213-8587(24)00363-2","DOIUrl":"https://doi.org/10.1016/s2213-8587(24)00363-2","url":null,"abstract":"The extent to which newer, incretin-based drugs for obesity improve disease outcomes via weight loss versus the direct effects of these drugs is the subject of intense interest. Although reductions in major adverse cardiovascular events appear to be predominantly driven by the direct tissue effects of such drugs, the associated weight loss effects must be relevant to the benefits observed in other major outcomes, albeit to differing extents. In this Personal View, we draw on evidence to support that weight loss is at least partly responsible (albeit to differing extents) for the reported benefits of incretin-based drugs for obesity in people living with heart failure with preserved ejection fraction, hypertension, chronic kidney disease, and type 2 diabetes. Concurrently, we propose that drug-induced weight loss is largely responsible for the reported improvements in osteoarthritis, obstructive sleep apnoea, and metabolic dysfunction-associated steatohepatitis outcomes. However, more evidence is needed to solidify these observations, including, when possible, trials comparing the effects of incretin-based drugs for obesity with calorie-reduced diets on both outcomes and mechanistic pathways. Such evidence has implications for public health and the design of future trials of novel drugs for obesity.","PeriodicalId":48790,"journal":{"name":"The Lancet Diabetes & Endocrinology","volume":"13 1","pages":""},"PeriodicalIF":44.5,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031082","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}
Pub Date : 2025-01-24DOI: 10.1016/s2213-8587(24)00313-9
Frederick J Raal, Vimal Mehta, Meral Kayikcioglu, Dirk Blom, Preeti Gupta, Avishay Elis, Traci Turner, Chris Daniels, Jeffrey Vest, Tracy Mitchell, Kate Caldwell, El Mustapha Bahassi, David Kallend, Evan A Stein
<h3>Background</h3>Lerodalcibep, a small binding anti-PCSK9 protein (adnectin), showed effective LDL cholesterol reduction in heterozygous familial hypercholesterolaemia. We aimed to assess the safety and efficacy of lerodalcibep and evolocumab in a globally diverse homozygous familial hypercholesterolaemia population.<h3>Methods</h3>This phase 3, randomised, open-label, crossover, non-inferiority study consisted of two 24-week treatment periods separated by an 8-week washout. The study was conducted in 12 lipid clinics in six countries (India, Israel, Norway, South Africa, Türkiye, and the USA). Patients aged 10 years or older with genetically confirmed homozygous familial hypercholesterolaemia were randomly assigned by computer-generated randomisation scheme performed centrally via interactive response technology to either monthly lerodalcibep 300 mg (1·2 mL subcutaneous injection) or monthly evolocumab 420 mg (subcutaneous 9 min infusion of 3·5 mL) for 24 weeks (period A) followed by an 8-week washout and then crossed over to the alternate therapy for the next 24 weeks (period B). The trial was open label, but all efficacy parameters were masked to patients, study staff, and the sponsor from randomisation. The primary efficacy endpoint was the percent change from baseline (day 1 of period A) in LDL cholesterol concentration to week 24 for period A and B. The intention-to-treat (ITT) population, defined as all randomly assigned patients, was used for the primary analysis. The safety population included all patients who received any study medication. The margin used to establish non-inferiority was 6%. The trial is registered with <span><span>ClinicalTrials.gov</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span> (<span><span>NCT04034485</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span>) and EudraCT (2019–003611–62), and has now finished.<h3>Findings</h3>Patients were enrolled from Nov 11, 2019, to July 2, 2021, and the final study visit took place on Aug 8, 2022. Of 82 patients screened, 66 entered period A (ITT population). The mean age was 28·7 years (SD 15·2); 20 (30%) of 66 were paediatric patients; 36 (55%) of 66 were female and 30 (45%) of 66 were male; and the mean baseline LDL cholesterol was 10·59 mmol/L (SD 4·37). Mean LDL cholesterol reduction by ITT analysis at week 24 was –4·9% (SE 3·5) on lerodalcibep compared with –10·3% (3·5) on evolocumab; the mean difference between treatments was 5·4% (95% CI –0·2 to 11·1), which did not show non-inferiority at the prespecified 6% margin. LDL cholesterol response varied considerably across the patient population but was generally similar in the same patients with both lerodalci
{"title":"Lerodalcibep and evolocumab for the treatment of homozygous familial hypercholesterolaemia with PCSK9 inhibition (LIBerate-HoFH): a phase 3, randomised, open-label, crossover, non-inferiority trial","authors":"Frederick J Raal, Vimal Mehta, Meral Kayikcioglu, Dirk Blom, Preeti Gupta, Avishay Elis, Traci Turner, Chris Daniels, Jeffrey Vest, Tracy Mitchell, Kate Caldwell, El Mustapha Bahassi, David Kallend, Evan A Stein","doi":"10.1016/s2213-8587(24)00313-9","DOIUrl":"https://doi.org/10.1016/s2213-8587(24)00313-9","url":null,"abstract":"<h3>Background</h3>Lerodalcibep, a small binding anti-PCSK9 protein (adnectin), showed effective LDL cholesterol reduction in heterozygous familial hypercholesterolaemia. We aimed to assess the safety and efficacy of lerodalcibep and evolocumab in a globally diverse homozygous familial hypercholesterolaemia population.<h3>Methods</h3>This phase 3, randomised, open-label, crossover, non-inferiority study consisted of two 24-week treatment periods separated by an 8-week washout. The study was conducted in 12 lipid clinics in six countries (India, Israel, Norway, South Africa, Türkiye, and the USA). Patients aged 10 years or older with genetically confirmed homozygous familial hypercholesterolaemia were randomly assigned by computer-generated randomisation scheme performed centrally via interactive response technology to either monthly lerodalcibep 300 mg (1·2 mL subcutaneous injection) or monthly evolocumab 420 mg (subcutaneous 9 min infusion of 3·5 mL) for 24 weeks (period A) followed by an 8-week washout and then crossed over to the alternate therapy for the next 24 weeks (period B). The trial was open label, but all efficacy parameters were masked to patients, study staff, and the sponsor from randomisation. The primary efficacy endpoint was the percent change from baseline (day 1 of period A) in LDL cholesterol concentration to week 24 for period A and B. The intention-to-treat (ITT) population, defined as all randomly assigned patients, was used for the primary analysis. The safety population included all patients who received any study medication. The margin used to establish non-inferiority was 6%. The trial is registered with <span><span>ClinicalTrials.gov</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span> (<span><span>NCT04034485</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>) and EudraCT (2019–003611–62), and has now finished.<h3>Findings</h3>Patients were enrolled from Nov 11, 2019, to July 2, 2021, and the final study visit took place on Aug 8, 2022. Of 82 patients screened, 66 entered period A (ITT population). The mean age was 28·7 years (SD 15·2); 20 (30%) of 66 were paediatric patients; 36 (55%) of 66 were female and 30 (45%) of 66 were male; and the mean baseline LDL cholesterol was 10·59 mmol/L (SD 4·37). Mean LDL cholesterol reduction by ITT analysis at week 24 was –4·9% (SE 3·5) on lerodalcibep compared with –10·3% (3·5) on evolocumab; the mean difference between treatments was 5·4% (95% CI –0·2 to 11·1), which did not show non-inferiority at the prespecified 6% margin. LDL cholesterol response varied considerably across the patient population but was generally similar in the same patients with both lerodalci","PeriodicalId":48790,"journal":{"name":"The Lancet Diabetes & Endocrinology","volume":"3 1","pages":""},"PeriodicalIF":44.5,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031079","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}
Pub Date : 2025-01-24DOI: 10.1016/s2213-8587(24)00364-4
Laura Abaandou, Raisa Ghosh, Joanna Klubo-Gwiezdzinska
The hypothalamic–pituitary–thyroid axis plays a crucial role in the pathogenesis, diagnosis, risk stratification, effectiveness of radioiodine therapy, and treatment response evaluation in epithelial thyroid cancer. Supraphysiological doses of levothyroxine are used in patients with intermediate-risk and high-risk thyroid cancer to suppress thyroid-stimulating hormone (TSH) to prevent tumour progression. However, free thyroxine and tri-iodothyronine have also been found to promote tumour growth in thyroid cancer preclinical models. Moreover, current evidence remains inconclusive about the role of TSH suppression in improving survival outcomes and reveals an increased risk of cardiovascular and skeletal adverse events after long-term exposure to excess levothyroxine. Stimulation of the axis with either recombinant human TSH or thyroid hormone withdrawal has been proven equally effective for diagnostic purposes and for facilitating radioiodine uptake for thyroid remnant ablation, but evidence is insufficient for non-inferiority of recombinant human TSH-based vs thyroid hormone withdrawal-based stimulation before radioiodine therapy of distant metastases.
{"title":"The role of the hypothalamic–pituitary–thyroid axis in thyroid cancer","authors":"Laura Abaandou, Raisa Ghosh, Joanna Klubo-Gwiezdzinska","doi":"10.1016/s2213-8587(24)00364-4","DOIUrl":"https://doi.org/10.1016/s2213-8587(24)00364-4","url":null,"abstract":"The hypothalamic–pituitary–thyroid axis plays a crucial role in the pathogenesis, diagnosis, risk stratification, effectiveness of radioiodine therapy, and treatment response evaluation in epithelial thyroid cancer. Supraphysiological doses of levothyroxine are used in patients with intermediate-risk and high-risk thyroid cancer to suppress thyroid-stimulating hormone (TSH) to prevent tumour progression. However, free thyroxine and tri-iodothyronine have also been found to promote tumour growth in thyroid cancer preclinical models. Moreover, current evidence remains inconclusive about the role of TSH suppression in improving survival outcomes and reveals an increased risk of cardiovascular and skeletal adverse events after long-term exposure to excess levothyroxine. Stimulation of the axis with either recombinant human TSH or thyroid hormone withdrawal has been proven equally effective for diagnostic purposes and for facilitating radioiodine uptake for thyroid remnant ablation, but evidence is insufficient for non-inferiority of recombinant human TSH-based <em>vs</em> thyroid hormone withdrawal-based stimulation before radioiodine therapy of distant metastases.","PeriodicalId":48790,"journal":{"name":"The Lancet Diabetes & Endocrinology","volume":"47 1","pages":""},"PeriodicalIF":44.5,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031083","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}
Pub Date : 2025-01-24DOI: 10.1016/s2213-8587(24)00347-4
Robert A Hegele
No Abstract
{"title":"Protein-binding therapy: a new approach to lower cholesterol","authors":"Robert A Hegele","doi":"10.1016/s2213-8587(24)00347-4","DOIUrl":"https://doi.org/10.1016/s2213-8587(24)00347-4","url":null,"abstract":"No Abstract","PeriodicalId":48790,"journal":{"name":"The Lancet Diabetes & Endocrinology","volume":"113 1","pages":""},"PeriodicalIF":44.5,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031084","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}
Pub Date : 2025-01-20DOI: 10.1016/s2213-8587(24)00335-8
John W Ostrominski, Vanita R Aroda
No Abstract
没有抽象的
{"title":"The STEP-HFpEF programme: advancing care at the intersections","authors":"John W Ostrominski, Vanita R Aroda","doi":"10.1016/s2213-8587(24)00335-8","DOIUrl":"https://doi.org/10.1016/s2213-8587(24)00335-8","url":null,"abstract":"No Abstract","PeriodicalId":48790,"journal":{"name":"The Lancet Diabetes & Endocrinology","volume":"74 1","pages":""},"PeriodicalIF":44.5,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142990890","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}
Pub Date : 2025-01-20DOI: 10.1016/s2213-8587(24)00304-8
Melanie J Davies, Peter van der Meer, Subodh Verma, Shachi Patel, Khaja M Chinnakondepalli, Barry A Borlaug, Javed Butler, Dalane W Kitzman, Sanjiv J Shah, Signe Harring, Afshin Salsali, Søren Rasmussen, Dirk von Lewinski, Walter Abhayaratna, Mark C Petrie, Mikhail N Kosiborod
<h3>Background</h3>About half of patients with heart failure with mildly reduced or preserved ejection fraction (HFpEF) have type 2 diabetes. In the STEP-HFpEF DM trial of adults with obesity-related HFpEF and type 2 diabetes, subcutaneous once weekly semaglutide 2·4 mg conferred improvements in heart failure-related symptoms and physical limitations, bodyweight, and other heart failure outcomes. We aimed to determine whether these effects of semaglutide differ according to baseline HbA<sub>1c</sub>.<h3>Methods</h3>STEP-HFpEF DM, a double-blind, randomised, placebo-controlled trial conducted at 108 clinical research sites across 16 countries in Asia, Europe, and North and South America, included individuals aged 18 years or older with documented HFpEF (left ventricular ejection fraction ≥45%), type 2 diabetes, and obesity (BMI ≥30 kg/m<sup>2</sup>). Participants were randomly assigned (1:1), with a block size of four within each stratum using an interactive web response system, stratified by baseline BMI (<35 kg/m<sup>2</sup> <em>vs</em> ≥35 kg/m<sup>2</sup>), to receive either semaglutide 2·4 mg or placebo subcutaneously. The effects of semaglutide versus placebo on the efficacy endpoints were evaluated by HbA<sub>1c</sub> categories at baseline: low (<6·5%; <48 mmol/mol), medium (6·5% to <7·5%; 48 mmol/mol to <58 mmol/mol), and high (≥7·5%; ≥58 mmol/mol). The dual primary endpoints were change in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) and bodyweight percentage from baseline to 52 weeks and were assessed in all randomly assigned participants by intention to treat. Hypoglycaemia events were also analysed to assess safety in all randomly assigned participants who received at least one dose of study drug. This trial is registered with <span><span>ClinicalTrials.gov</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span>, <span><span>NCT04916470</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span>.<h3>Findings</h3>Between June 27, 2021 and Sept 2, 2022, 616 participants were enrolled and randomly assigned (mean age 68·4 years [SD 8·9]; 273 [44%] were female, 343 [56%] were male, and 519 [84%] were White). The low baseline HbA<sub>1c</sub> group included 227 participants (112 assigned to semaglutide and 115 to placebo), the medium baseline HbA<sub>1c</sub> group included 226 participants (124 assigned to semaglutide and 102 to placebo), and the high baseline HbA<sub>1c</sub> group included 163 participants (74 assigned to semaglutide and 89 to placebo). The median duration of follow-up in the overall trial was 401 days (IQR 400–405). The change in KCCQ-CSS from baseline to 52 weeks was 1
{"title":"Semaglutide in obesity-related heart failure with preserved ejection fraction and type 2 diabetes across baseline HbA1c levels (STEP-HFpEF DM): a prespecified analysis of heart failure and metabolic outcomes from a randomised, placebo-controlled trial","authors":"Melanie J Davies, Peter van der Meer, Subodh Verma, Shachi Patel, Khaja M Chinnakondepalli, Barry A Borlaug, Javed Butler, Dalane W Kitzman, Sanjiv J Shah, Signe Harring, Afshin Salsali, Søren Rasmussen, Dirk von Lewinski, Walter Abhayaratna, Mark C Petrie, Mikhail N Kosiborod","doi":"10.1016/s2213-8587(24)00304-8","DOIUrl":"https://doi.org/10.1016/s2213-8587(24)00304-8","url":null,"abstract":"<h3>Background</h3>About half of patients with heart failure with mildly reduced or preserved ejection fraction (HFpEF) have type 2 diabetes. In the STEP-HFpEF DM trial of adults with obesity-related HFpEF and type 2 diabetes, subcutaneous once weekly semaglutide 2·4 mg conferred improvements in heart failure-related symptoms and physical limitations, bodyweight, and other heart failure outcomes. We aimed to determine whether these effects of semaglutide differ according to baseline HbA<sub>1c</sub>.<h3>Methods</h3>STEP-HFpEF DM, a double-blind, randomised, placebo-controlled trial conducted at 108 clinical research sites across 16 countries in Asia, Europe, and North and South America, included individuals aged 18 years or older with documented HFpEF (left ventricular ejection fraction ≥45%), type 2 diabetes, and obesity (BMI ≥30 kg/m<sup>2</sup>). Participants were randomly assigned (1:1), with a block size of four within each stratum using an interactive web response system, stratified by baseline BMI (<35 kg/m<sup>2</sup> <em>vs</em> ≥35 kg/m<sup>2</sup>), to receive either semaglutide 2·4 mg or placebo subcutaneously. The effects of semaglutide versus placebo on the efficacy endpoints were evaluated by HbA<sub>1c</sub> categories at baseline: low (<6·5%; <48 mmol/mol), medium (6·5% to <7·5%; 48 mmol/mol to <58 mmol/mol), and high (≥7·5%; ≥58 mmol/mol). The dual primary endpoints were change in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) and bodyweight percentage from baseline to 52 weeks and were assessed in all randomly assigned participants by intention to treat. Hypoglycaemia events were also analysed to assess safety in all randomly assigned participants who received at least one dose of study drug. This trial is registered with <span><span>ClinicalTrials.gov</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>, <span><span>NCT04916470</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>.<h3>Findings</h3>Between June 27, 2021 and Sept 2, 2022, 616 participants were enrolled and randomly assigned (mean age 68·4 years [SD 8·9]; 273 [44%] were female, 343 [56%] were male, and 519 [84%] were White). The low baseline HbA<sub>1c</sub> group included 227 participants (112 assigned to semaglutide and 115 to placebo), the medium baseline HbA<sub>1c</sub> group included 226 participants (124 assigned to semaglutide and 102 to placebo), and the high baseline HbA<sub>1c</sub> group included 163 participants (74 assigned to semaglutide and 89 to placebo). The median duration of follow-up in the overall trial was 401 days (IQR 400–405). The change in KCCQ-CSS from baseline to 52 weeks was 1","PeriodicalId":48790,"journal":{"name":"The Lancet Diabetes & Endocrinology","volume":"30 1","pages":""},"PeriodicalIF":44.5,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142990889","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}
Pub Date : 2025-01-14DOI: 10.1016/s2213-8587(24)00316-4
Francesco Rubino, David E Cummings, Robert H Eckel, Ricardo V Cohen, John P H Wilding, Wendy A Brown, Fatima Cody Stanford, Rachel L Batterham, I Sadaf Farooqi, Nathalie J Farpour-Lambert, Carel W le Roux, Naveed Sattar, Louise A Baur, Katherine M Morrison, Anoop Misra, Takashi Kadowaki, Kwang Wei Tham, Priya Sumithran, W Timothy Garvey, John P Kirwan, Geltrude Mingrone
<h2>Section snippets</h2><section><section><h2>Executive summary</h2>Current BMI-based measures of obesity can both underestimate and overestimate adiposity and provide inadequate information about health at the individual level, which undermines medically-sound approaches to health care and policy. This Commission sought to define clinical obesity as a condition of illness that, akin to the notion of chronic disease in other medical specialties, directly results from the effect of excess adiposity on the function of organs and tissues. The specific aim of the</section></section><section><section><section><h2>Conception of the Commission</h2>The idea and general plan to convene a global expert group for the definition of diagnostic criteria of chronic illness in obesity (clinical obesity) was conceived by FR, and discussed with editors of <em>The Lancet Diabetes & Endocrinology</em> journal for consideration as a <em>Lancet</em> Commission. The Commission on clinical obesity was organised in partnership with the Institute of Diabetes, Endocrinology and Obesity at Kings Health Partners. Additional scientific input about the programme of the</section></section></section><section><section><section><h2>General principles</h2>Although the notion of disease might seem obvious, a clear definition of disease does not exist. One comprehensive approach to the definition of disease was proposed by Stanley Heshka and David Allison:<sup>27</sup> (A) a condition of the body, its parts, organs, or systems, or an alteration thereof; (B) resulting from infection, parasites, nutritional, dietary, environmental, genetic, or other causes; (C) having a characteristic, identifiable, marked group of symptoms or signs; and (D) deviation from</section></section></section><section><section><h2>Commissioners' views on obesity as a disease</h2>The idea of obesity as a disease was a controversial subject also within this Commission. Initial opinions diverged substantially, clearly indicating that a consensus would not be reached on a blanket definition of obesity as a disease, at least as currently defined. A specific pre-Delphi survey on the question of whether obesity is a disease showed that more than half of the commissioners rejected the all-or-nothing scenario implied in the question, but supported the view that obesity is a</section></section><section><section><section><h2>Conceptual and practical issues in the current definition of obesity</h2>Obesity is currently conceived and defined as a condition of excess adiposity that presents a “risk to health”.<sup>34</sup> The current diagnosis of obesity worldwide is based on BMI, calculated as weight in kilograms divided by height in metres squared. According to WHO, an adult with a BMI of 30 kg/m<sup>2</sup> or higher is considered to have obesity.This definition has been widely adopted and used in epidemiological studies, clinical practice, and public health policy.<sup>35</sup> However, several studies have shown t
当前基于bmi的肥胖测量既可能低估肥胖，也可能高估肥胖，而且提供的个人健康信息不足，这破坏了医疗保健和政策的医学上合理的方法。该委员会试图将临床肥胖定义为一种疾病，这种疾病与其他医学专业中的慢性病概念类似，是过度肥胖对器官和组织功能的影响直接导致的。委员会构想的具体目的是召集一个全球专家组来定义肥胖慢性疾病（临床肥胖）诊断标准的构想和总体计划，由FR构想，并与《柳叶刀糖尿病》的编辑进行了讨论；作为柳叶刀委员会考虑的内分泌学杂志。临床肥胖委员会是与国王健康伙伴的糖尿病、内分泌学和肥胖研究所合作组织的。关于《一般原则》计划的额外科学投入尽管疾病的概念似乎很明显，但并不存在对疾病的明确定义。斯坦利·赫什卡（Stanley Heshka）和大卫·艾利森（David Allison）提出了一种关于疾病定义的综合方法：27 (A)身体、身体各部分、器官或系统的状况，或其变化；(B)由感染、寄生虫、营养、饮食、环境、遗传或其他原因引起的；(C)具有特征性的、可识别的、明显的一组症状或体征；(D)委员们对肥胖作为一种疾病的看法的偏差。肥胖作为一种疾病的观点在委员会内部也是一个有争议的话题。最初的意见分歧很大，清楚地表明，不可能就肥胖作为一种疾病的笼统定义达成共识，至少不可能像目前的定义那样。34 .针对肥胖是否是一种疾病这一问题，在德尔菲前进行了一项具体的调查，结果显示，半数以上的委员拒绝接受问题中暗示的“要么全有，要么全无”的观点，但支持这样一种观点，即肥胖在目前对肥胖的定义中是一个概念上和实际上的问题目前世界范围内对肥胖的诊断是基于身体质量指数，计算方法是体重（公斤）除以身高（米）的平方。根据世界卫生组织，成年人的身体质量指数为30 kg/m2或更高被认为是肥胖。这一定义已被广泛采用，并用于流行病学研究、临床实践和公共卫生政策然而，一些研究表明，患者、卫生保健专业人员和政策制定者对肥胖的看法和态度围绕肥胖作为一种疾病的观点的辩论引发了两极分化，往往是基于非医学考虑的情绪反应。支持这一想法的人经常引用这样一个事实，即这样做可以最大限度地减少基于体重的耻辱和歧视，因为它转移了人们对个人的指责。这一结果似乎是合理的，而且确实是可取的，但这并不是一种医疗状况应该被视为疾病的理由。对这一观点持批评态度的人担心，重新定义肥胖及其临床特征肥胖可能会增加患其他疾病和过早死亡的风险，或者本身就会引发疾病，或者两者兼而有之。因此，有必要对肥胖的病因、病理生理和临床特征进行更好的描述。虽然替代的人体测量和生物标志物已被建议作为BMI的诊断工具或治疗决策的可能替代品，但它们尚未被用作个体患者健康的衡量标准，并且作为持续疾病的衡量标准的诊断准确性不足。在其他医学领域，疾病的诊断通常是基于对器官或整个机体功能障碍引起的体征和症状的检测（见肥胖的原因）肥胖的原因是多因素的，而且尚未完全了解。2,5,80遗传、环境、心理、营养和代谢因素可诱导维持脂肪组织正常质量、分布和功能的生物学机制发生改变，从而导致肥胖。身体脂肪的积累是正能量平衡的一个功能，即大量营养素的出现速度超过消失速度。成人肥胖直接引起器官功能障碍的临床表现肥胖可通过多种病理生理机制直接引起器官功能障碍，包括脂肪组织质量增加的物理效应、组织和器官内异位脂肪的存在、代谢效应、炎症机制和心理后果（图3）。 器官功能障碍和肥胖并发症的发展，无论是心脏代谢还是生物力学，都可能在不同的个体中出现不同程度的肥胖。此外，儿童和青少年肥胖的严重程度已经成为世界范围内一个主要的健康、社会和经济负担在5-19岁的儿童和青少年中，超重和肥胖的患病率大幅上升，从1975年的4%上升到2016年的18%以上。在这一年龄组中，全球肥胖患病率从1975年的1%上升到2016年的7%（女孩占6%，男孩占8%），有超过1.24亿儿童和青少年患有这一疾病。肥胖可早发：2019年《儿童青少年肥胖直接导致的器官功能障碍临床表现》本节综述了儿童青少年临床肥胖的主要表现，描述了过度肥胖如何影响主要器官、组织和身体系统，导致健康不良。然而，与成年人一样，肥胖也会促进肥胖相关疾病或失调的发展，从而增加儿童和成年时期发病率、死亡率和生活质量的风险，如果肥胖得不到治疗的话。委员会建议：临床肥胖的定义和诊断标准委员会的结论和建议是通过对证据和观点的广泛讨论得出的，加上一个正式的共识发展过程，以产生专家组中最多数人支持的建议。所有的定义、建议和诊断标准都是由专家组内一致或近乎一致的共识达成的。所有基于共识的结论和建议，每个结论和建议都有其相关的委员会的优势和局限性。我们承认本委员会工作中的一些局限性。委员们采用了一种类似德尔菲的方法来得出共同的结论。德尔菲技术的迭代特性具有内在的局限性，并可能导致群体思维，其中参与者可能符合群体的主导意见，这可能影响客观性然而，广泛使用现场和离线的德尔菲前调查，并在较小的小组（小组委员会）内进行讨论，得出结论：肥胖作为一种疾病的观点是现代医学中最具争议和两极分化的辩论之一，对受影响的人群和整个社会具有广泛而深远的影响。肥胖的最初定义是“对健康构成风险的状况”，与之一致的是，肥胖被认为是其他疾病的先兆，并被广泛研究。然而，肥胖作为一种疾病的表现还没有得到充分的描述。缺乏临床利益声明fr宣布从Ethicon (Johnson &；强生)、诺和诺德和美敦力；Morphic Medical的咨询费；美敦力、Ethicon、诺和诺德、礼来和安进公司致词；曾担任Keyron科学顾问委员会成员（无薪），GI Metabolic Solutions数据安全和监测委员会成员；是代谢健康研究所（非营利）的主席；也是国际代谢健康协会和伦敦代谢协会的唯一主任。临床肥胖内分泌委员会是由King's Health Partners的糖尿病、内分泌和肥胖研究所合作组织的。King's Health Partners为组织在线会议、内部沟通和达成共识进程提供后勤和行政支持。我们要感谢King's Health Partners的糖尿病、内分泌和肥胖研究所提供的宝贵支持。在
{"title":"Definition and diagnostic criteria of clinical obesity","authors":"Francesco Rubino, David E Cummings, Robert H Eckel, Ricardo V Cohen, John P H Wilding, Wendy A Brown, Fatima Cody Stanford, Rachel L Batterham, I Sadaf Farooqi, Nathalie J Farpour-Lambert, Carel W le Roux, Naveed Sattar, Louise A Baur, Katherine M Morrison, Anoop Misra, Takashi Kadowaki, Kwang Wei Tham, Priya Sumithran, W Timothy Garvey, John P Kirwan, Geltrude Mingrone","doi":"10.1016/s2213-8587(24)00316-4","DOIUrl":"https://doi.org/10.1016/s2213-8587(24)00316-4","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Executive summary</h2>Current BMI-based measures of obesity can both underestimate and overestimate adiposity and provide inadequate information about health at the individual level, which undermines medically-sound approaches to health care and policy. This Commission sought to define clinical obesity as a condition of illness that, akin to the notion of chronic disease in other medical specialties, directly results from the effect of excess adiposity on the function of organs and tissues. The specific aim of the</section></section><section><section><section><h2>Conception of the Commission</h2>The idea and general plan to convene a global expert group for the definition of diagnostic criteria of chronic illness in obesity (clinical obesity) was conceived by FR, and discussed with editors of <em>The Lancet Diabetes & Endocrinology</em> journal for consideration as a <em>Lancet</em> Commission. The Commission on clinical obesity was organised in partnership with the Institute of Diabetes, Endocrinology and Obesity at Kings Health Partners. Additional scientific input about the programme of the</section></section></section><section><section><section><h2>General principles</h2>Although the notion of disease might seem obvious, a clear definition of disease does not exist. One comprehensive approach to the definition of disease was proposed by Stanley Heshka and David Allison:<sup>27</sup> (A) a condition of the body, its parts, organs, or systems, or an alteration thereof; (B) resulting from infection, parasites, nutritional, dietary, environmental, genetic, or other causes; (C) having a characteristic, identifiable, marked group of symptoms or signs; and (D) deviation from</section></section></section><section><section><h2>Commissioners' views on obesity as a disease</h2>The idea of obesity as a disease was a controversial subject also within this Commission. Initial opinions diverged substantially, clearly indicating that a consensus would not be reached on a blanket definition of obesity as a disease, at least as currently defined. A specific pre-Delphi survey on the question of whether obesity is a disease showed that more than half of the commissioners rejected the all-or-nothing scenario implied in the question, but supported the view that obesity is a</section></section><section><section><section><h2>Conceptual and practical issues in the current definition of obesity</h2>Obesity is currently conceived and defined as a condition of excess adiposity that presents a “risk to health”.<sup>34</sup> The current diagnosis of obesity worldwide is based on BMI, calculated as weight in kilograms divided by height in metres squared. According to WHO, an adult with a BMI of 30 kg/m<sup>2</sup> or higher is considered to have obesity.This definition has been widely adopted and used in epidemiological studies, clinical practice, and public health policy.<sup>35</sup> However, several studies have shown t","PeriodicalId":48790,"journal":{"name":"The Lancet Diabetes & Endocrinology","volume":"31 1","pages":""},"PeriodicalIF":44.5,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981447","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：