{"title":"Putting wellbeing at the core of diabetes care","authors":"","doi":"10.1016/s2213-8587(24)00345-0","DOIUrl":"https://doi.org/10.1016/s2213-8587(24)00345-0","url":null,"abstract":"No Abstract","PeriodicalId":48790,"journal":{"name":"The Lancet Diabetes & Endocrinology","volume":"216 1","pages":""},"PeriodicalIF":44.5,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142609767","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}
Jesús Argente, Charles F Verge, Uzoma Okorie, Ilene Fennoy, Megan M Kelsey, Casey Cokkinias, Cecilia Scimia, Hak-Myung Lee, I Sadaf Farooqi
{"title":"Setmelanotide in patients aged 2–5 years with rare MC4R pathway-associated obesity (VENTURE): a 1 year, open-label, multicenter, phase 3 trial","authors":"Jesús Argente, Charles F Verge, Uzoma Okorie, Ilene Fennoy, Megan M Kelsey, Casey Cokkinias, Cecilia Scimia, Hak-Myung Lee, I Sadaf Farooqi","doi":"10.1016/s2213-8587(24)00273-0","DOIUrl":"https://doi.org/10.1016/s2213-8587(24)00273-0","url":null,"abstract":"<h3>Background</h3>Setmelanotide, a melanocortin-4 receptor (MC4R) agonist, has been shown to reduce hunger and weight in patients aged 6 years and older with proopiomelanocortin (POMC) deficiency (including biallelic variants in proprotein convertase subtilisin/kexin type 1 [<em>PCSK1</em>]), leptin receptor (LEPR) deficiency, or Bardet-Biedl syndrome (BBS). No approved therapies for patients younger than 6 years old currently exist. The phase 3, open-label VENTURE trial aimed to evaluate the efficacy and safety of setmelanotide in patients aged 2–5 years with POMC or LEPR deficiency or BBS.<h3>Methods</h3>This phase 3, open-label, multicentre trial, conducted across six sites in the USA, the UK, Spain, and Australia, enrolled eligible patients aged 2–5 years who had hyperphagia and obesity due to biallelic <em>POMC</em> (including <em>PCSK1</em>) or <em>LEPR</em> variants or genetically confirmed BBS. Open-label subcutaneous setmelanotide was administered once daily for 52 weeks, starting at 0·5 mg with doses increasing every 2 weeks in 0·5 mg increments until reaching the maximum dose based on weight. The co-primary endpoints at week 52 were the percentage of patients reaching a 0·2-point decrease or greater in BMI Z score (a statistical measure used to assess BMI in paediatric patients considering a patient's BMI and comparing it to reference values for the same age and sex) and mean percent change in BMI. Additional endpoints measured safety, hunger, weight-related outcomes, and caregiver burden. 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> (<span><span>NCT04966741</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 is complete.<h3>Findings</h3>Between March 8, 2022, and Sept 18, 2023, 13 patients were screened at the six sites, and 12 patients were enrolled in the study (seven with POMC or LEPR and five with BBS); one patient with BBS was excluded as their BMI was not at the 97th percentile or above. Of the 12 patients enrolled, most were male (seven [58%] <em>vs</em> five [42%] for female) and the mean age was 3·6 years (SD 0·9). 11 patients completed the trial. Ten (83%) of the 12 overall participants reached a 0·2-point reduction or more in BMI Z score per WHO methodology at week 52 (95% CI 58·7–99·8). The mean percent change in BMI from baseline at week 52 was −18% (SD 13) in the overall safety population. Mean percent change in BMI at week 52 was −26% (SD 11) in patients with POMC or LEPR deficiency and −10% (9) in patients with BBS. Mean reductions in secondary endpoints of BMI Z score (3·4 [2·5]) and percent of the BMI 95th percentile (32·5 [22·9]) we","PeriodicalId":48790,"journal":{"name":"The Lancet Diabetes & Endocrinology","volume":"39 1","pages":""},"PeriodicalIF":44.5,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142609769","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}
{"title":"Setmelanotide for the treatment of severe early-childhood genetic obesity","authors":"Christian L Roth","doi":"10.1016/s2213-8587(24)00312-7","DOIUrl":"https://doi.org/10.1016/s2213-8587(24)00312-7","url":null,"abstract":"No Abstract","PeriodicalId":48790,"journal":{"name":"The Lancet Diabetes & Endocrinology","volume":"5 1","pages":""},"PeriodicalIF":44.5,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142609768","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}
Jesús Argente, I Sadaf Farooqi, Julie A Chowen, Peter Kühnen, Miguel López, Eugenia Morselli, Hoong-Wei Gan, Helen A Spoudeas, Martin Wabitsch, Manuel Tena-Sempere
{"title":"Hypothalamic obesity: from basic mechanisms to clinical perspectives","authors":"Jesús Argente, I Sadaf Farooqi, Julie A Chowen, Peter Kühnen, Miguel López, Eugenia Morselli, Hoong-Wei Gan, Helen A Spoudeas, Martin Wabitsch, Manuel Tena-Sempere","doi":"10.1016/s2213-8587(24)00283-3","DOIUrl":"https://doi.org/10.1016/s2213-8587(24)00283-3","url":null,"abstract":"Despite the diverse nature of obesity, there is compelling genetic, clinical, and experimental evidence that endorses the important contribution of brain circuits to this condition. The hypothalamus contains major regulatory circuits for bodyweight homoeostasis, the deregulation of which can lead to obesity. Although functional perturbation of hypothalamic pathways could lie at the basis of common forms of obesity, the term hypothalamic obesity has been created to define those rare forms of severe obesity where a clear hypothalamic substrate can be identified, either of genetic or acquired origin. An in-depth understanding of the pathogenesis, clinical presentation, and therapeutic targets of hypothalamic obesity relies on the comprehension of the physiological basis of hypothalamic pathways governing bodyweight control, the mechanisms (either genetic or acquired) whereby they are perturbed, and the consequences of such perturbation. In this Review, we provide a synoptic overview of hypothalamic obesity, from basic mechanisms to clinical perspectives, with a major focus on current developments and new avenues for the diagnosis and precise treatment of these rare forms of obesity.","PeriodicalId":48790,"journal":{"name":"The Lancet Diabetes & Endocrinology","volume":"19 1","pages":""},"PeriodicalIF":44.5,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601202","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}
Dianna J Magliano, Lei Chen, Jedidiah I Morton, Agus Salim, Bendix Carstensen, Edward W Gregg, Meda E Pavkov, Martti Arffman, Helen M Colhoun, Kyoung Hwa Ha, Tomoaki Imamura, György Jermendy, Dae Jung Kim, Zoltán Kiss, Didac Mauricio, Stuart J McGurnaghan, Yuichi Nishioka, Sarah H Wild, Klas Winell, Jonathan E Shaw
{"title":"Trends in the incidence of young-adult-onset diabetes by diabetes type: a multi-national population-based study from an international diabetes consortium","authors":"Dianna J Magliano, Lei Chen, Jedidiah I Morton, Agus Salim, Bendix Carstensen, Edward W Gregg, Meda E Pavkov, Martti Arffman, Helen M Colhoun, Kyoung Hwa Ha, Tomoaki Imamura, György Jermendy, Dae Jung Kim, Zoltán Kiss, Didac Mauricio, Stuart J McGurnaghan, Yuichi Nishioka, Sarah H Wild, Klas Winell, Jonathan E Shaw","doi":"10.1016/s2213-8587(24)00243-2","DOIUrl":"https://doi.org/10.1016/s2213-8587(24)00243-2","url":null,"abstract":"<h3>Background</h3>Population-based incidence data on young-adult-onset type 1 diabetes and type 2 diabetes are limited. We aimed to examine secular trends in the incidence of diagnosed type 1 diabetes and type 2 diabetes with an age of onset between 15 and 39 years.<h3>Methods</h3>In this multicountry aggregate data analysis, we assembled eight administrative datasets from high-income jurisdictions and countries (Australia, Denmark, Finland, Hungary, Japan, Scotland, South Korea, and Spain [Catalonia]) that had appropriate data available from an international diabetes consortium (GLOBODIAB) describing incidence by diabetes type among people aged 15–39 years from 2000 to 2020. We modelled type 1 diabetes and type 2 diabetes incidence rates using Poisson regression including age and calendar time by sex.<h3>Findings</h3>During the years 2000–20, there were 349 591 incident diabetes (both types) cases from 346 million person-years of follow-up among people aged 15–39 years. Over time, there was no statistically significant change in the incidence of type 1 diabetes in Hungary and Japan. The incidence of type 1 diabetes significantly increased in Australia, Denmark, Finland, Scotland, South Korea, and Spain, with annual changes ranging from 0·5% to 6·0%. The incidence of type 2 diabetes significantly increased in four of eight jurisdictions (Denmark, Finland, Japan, and South Korea), with annual increases from 2·0% to 8·5%. The magnitude of increase in incidence of type 2 diabetes was greater in Asian than non-Asian jurisdictions. There was no statistically significant change in type 2 diabetes incidence in Australia and Hungary. The incidence of type 2 diabetes significantly decreased in Scotland and Spain, with annual changes of –0·7% and –1·5%, respectively.<h3>Interpretation</h3>There is variability in the trajectory of the incidence of young-adult-onset type 2 diabetes among high-income countries or jurisdictions, with a greater evidence of increase in Asian than non-Asian countries. Evolving trends in the incidence of type 1 and type 2 diabetes in young adults call for the ongoing surveillance of diabetes incidence and a greater research focus on this population.<h3>Funding</h3>US Centers for Disease Control and Prevention, Diabetes Australia Research Programme, and Victoria State Government Operational Infrastructure Support Programme.","PeriodicalId":48790,"journal":{"name":"The Lancet Diabetes & Endocrinology","volume":"105 1","pages":""},"PeriodicalIF":44.5,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142598523","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}
Michael Bergman, Muhammad Abdul-Ghani, Juliana Chan, Maria Inês Schmidt, Joon Ha, Sang Soo Kim, Arthur S Sherman, Ram Jagannathan, Jaakko Tuomilehto
{"title":"Staging schema for early diagnosis of prediabetes","authors":"Michael Bergman, Muhammad Abdul-Ghani, Juliana Chan, Maria Inês Schmidt, Joon Ha, Sang Soo Kim, Arthur S Sherman, Ram Jagannathan, Jaakko Tuomilehto","doi":"10.1016/s2213-8587(24)00320-6","DOIUrl":"https://doi.org/10.1016/s2213-8587(24)00320-6","url":null,"abstract":"No Abstract","PeriodicalId":48790,"journal":{"name":"The Lancet Diabetes & Endocrinology","volume":"12 1","pages":""},"PeriodicalIF":44.5,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142597074","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}
Carla M Prado, Stuart M Phillips, M Cristina Gonzalez, Steven B Heymsfield
{"title":"Muscle matters: the effects of medically induced weight loss on skeletal muscle.","authors":"Carla M Prado, Stuart M Phillips, M Cristina Gonzalez, Steven B Heymsfield","doi":"10.1016/S2213-8587(24)00272-9","DOIUrl":"10.1016/S2213-8587(24)00272-9","url":null,"abstract":"","PeriodicalId":48790,"journal":{"name":"The Lancet Diabetes & Endocrinology","volume":" ","pages":"785-787"},"PeriodicalIF":44.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142299179","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}
Giulia Ferrannini, Jaakko Tuomilehto, Guy De Backer, Kornelia Kotseva, Linda Mellbin, Oliver Schnell, David Wood, Dirk De Bacquer, Lars Rydén
{"title":"Dysglycaemia screening and its prognostic impact in patients with coronary artery disease: experiences from the EUROASPIRE IV and V cohort studies.","authors":"Giulia Ferrannini, Jaakko Tuomilehto, Guy De Backer, Kornelia Kotseva, Linda Mellbin, Oliver Schnell, David Wood, Dirk De Bacquer, Lars Rydén","doi":"10.1016/S2213-8587(24)00201-8","DOIUrl":"10.1016/S2213-8587(24)00201-8","url":null,"abstract":"<p><strong>Background: </strong>Glucose perturbations can be detected by fasting plasma glucose (FPG), HbA<sub>1c</sub>, and the oral glucose tolerance test (OGTT). The highest yield is provided by OGTT. HbA<sub>1c</sub> is considered more practical. We compare the diagnostic and predictive performance of these glycaemic indicators based on combined data from the EUROASPIRE IV (EAIV) and V (EAV) studies.</p><p><strong>Methods: </strong>This cohort study was conducted in 79 centres in 24 European countries (EAIV) and 131 centres in 27 European countries (EAV). Eligible patients were aged 18-80 years, did not have diabetes, and were diagnosed with coronary artery disease 6-36 months (EAIV) or 6-24 months (EAV) before the investigation. Patients were investigated with OGTT (FPG and 2 h post-load glucose [2-hPG]) and HbA<sub>1c</sub>. Follow-up of subsequent cardiovascular events was done by means of a questionnaire at least 1 year after the baseline investigation. Analyses were done in patients with both OGTT and HbA<sub>1c</sub> data available. Outcome analysis in these patients was restricted to those with valid follow-up data available.</p><p><strong>Findings: </strong>16 259 patients were interviewed in EAIV (2012-13) and EAV (2016-17). 8364 patients had both OGTT and HbA<sub>1C</sub> data and were included in the analysis population (3932 in EAIV and 4432 in EAV). Information on cardiovascular events was available in 7892 patients. Follow-up was for a median 1·6 years (IQR 1·2-2·0). The average patient age was 63·3 years (SD 9·8), and 6346 (75·9%) of 8364 patients were men. At baseline, 1856 (22·5%) of 8263 patients were determined to have newly detected type 2 diabetes using OGTT alone, compared with 346 (4·2%) using HbA<sub>1c</sub> alone. New dysglycaemia, defined as newly detected type 2 diabetes or impaired glucose tolerance (IGT), was present in 3896 (47·1%) of the patients according to 2hPG. 2hPG 9 mmol/L or greater (162 mg/dL, adjusted hazard ratio [aHR] 1·58; 95% CI 1·27-1·95, p<0·0001), and HbA<sub>1c</sub> 5·9% or greater (41 mmol/mol, aHR 1·48, 1·19-1·84; p=0·0010) were the strongest predictors of cardiovascular events, while FPG did not predict. A multivariable model showed that the effect of HbA<sub>1c</sub> on cardiovascular events was mainly explained by 2hPG (aHR for 1 unit increase in HbA<sub>1c</sub> 1·13, 0·98-1·30; p=0·11; and aHR for 1 unit increase in Ln[2hPG] 1·37, 1·08-1·74; p=0·0042).</p><p><strong>Interpretation: </strong>2hPG appears better than HbA<sub>1c</sub> in detecting dysglycaemia and predicting its impact on future cardiovascular events in patients with coronary artery disease and should be recommended as the primary screening tool.</p><p><strong>Funding: </strong>Swedish Heart-Lung Foundation, Region Stockholm (ALF), the Erling Persson Foundation, the Baltic Child Foundation.</p>","PeriodicalId":48790,"journal":{"name":"The Lancet Diabetes & Endocrinology","volume":" ","pages":"790-798"},"PeriodicalIF":5.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330473","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}