The Lancet Diabetes & Endocrinology最新文献

{"title":"Multi-ancestry polygenic risk scores for the prediction of type 2 diabetes and complications in diverse ancestries.","authors":"Alicia Huerta-Chagoya, Joohyun Kim, Ravi Mandla, Yingchang Lu, Ken Suzuki, Lauren E Petty, Hong Kiat Ng, Jaewon Choi, Simon Lee, Madhusmita Rout, Kuang Lin, Katherine Taylor, Carlos A Aguilar-Salinas, Lourdes García-García, Clicerio González-Villalpando, Christopher A Haiman, Young Jin Kim, Soo Heon Kwak, Aaron Leong, Ruth J F Loos, Andres Moreno-Estrada, Andrew P Morris, Lorena Orozco, Jerome I Rotter, Dharambir Sanghera, Teresa Tusie-Luna, Benjamin F Voight, Marijana Vujkovic, Robin G Walters, Tian Ge, Alisa K Manning, Marie Loh, Jennifer E Below, Xueling Sim, Josep M Mercader, Maggie C Y Ng","doi":"10.1016/S2213-8587(25)00405-X","DOIUrl":"10.1016/S2213-8587(25)00405-X","url":null,"abstract":"<p><strong>Background: </strong>Polygenic risk scores (PRSs) improve prediction of the development of type 2 diabetes over the use of clinical risk factors alone; however, they perform poorly in populations of non-European ancestry, limiting their global clinical utility. We aimed to deliver comprehensive and rigorously tested multi-ancestry PRSs for prediction in type 2 diabetes.</p><p><strong>Methods: </strong>We conducted meta-analyses using data from type 2 diabetes genome-wide association studies (GWAS) across cohorts from five major global ancestries: European, African or African American, Admixed American, South Asian, and East Asian. We used summary statistics from the GWAS to construct single-ancestry PRSs (using the continuous-shrinkage PRS-CS method) and multi-ancestry PRSs (using the PRS-CSx method), and constructed ancestry-specific linkage disequilibrium panels to model pairwise correlations between single-nucleotide polymorphisms in GWAS during PRS construction. Models were validated for association with type 2 diabetes in at least four independent cohorts per ancestry. The effect sizes of PRSs were estimated as the odds ratio (OR) per SD of the PRS, and ORs for individuals at the 90th, 95th, and 97·5th PRS percentiles were compared with the IQR as a reference. We also tested our PRS models for prediction of diabetes incidence with or without additional clinical factors, as well as microvascular complications and comorbidities.</p><p><strong>Findings: </strong>Our analysis used data from 409 959 individuals with type 2 diabetes and 1 983 345 controls: respectively, 359 819 and 1 825 729 indivduals were included in the GWAS dataset, with 10 992 and 31 792 individuals in the training dataset and 39 148 and 125 824 individuals in the validation dataset. The best predictive performance for the single-ancestry PRSs was in European (incremental AUC 0·07-0·14) and East Asian (0·02-0·16) ancestries, whereas prediction was poorer for African or African American (0·02-0·03), Admixed American (0·02-0·04), and South Asian (0·02-0·04) ancestries, correlating with sample sizes in the GWAS. Compared with single-ancestry PRSs, our multi-ancestry PRSs showed higher effect sizes and smaller 95% CIs across all ancestries: OR per SD 1·73 (95% CI 1·67-1·80) in African or African American, 2·82 (2·67-2·97) in Admixed American, 2·45 (2·36-2·54) in East Asian, 2·36 (2·32-2·41) in European, and 2·23 (2·05-2·42) in South Asian ancestries. Individuals in the 97·5th PRS percentile had a 3-7 times increased risk of type 2 diabetes compared with those in the IQR (OR 3·43 [95% CI 2·80-4·21] in African or African American, 7·47 [5·64-9·89] in Admixed American, 6·62 [5·58-7·85] in East Asian, 6·25 [5·72-6·82] in European, and 4·50 [2·70-7·53] in South Asian ancestries). These PRSs were also associated with earlier onset of type 2 diabetes, higher risk of developing microvascular complications, and provide additional predictive value beyond clinical factors. In ind","PeriodicalId":48790,"journal":{"name":"The Lancet Diabetes & Endocrinology","volume":" ","pages":"558-569"},"PeriodicalIF":36.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13290298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147822537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of a 6-week subcutaneous infusion of native GIP alone or as add-on to semaglutide in people with type 2 diabetes: a single-centre, double-blind, parallel-group, randomised, placebo-controlled trial.","authors":"Mads M Helsted, Christiane Fonnesbech-Wulff, Nina L Schaltz, Ingrid W Lund, Julie L Forman, Casper K Nielsen, Anders Englund, Bolette Hartmann, Tina Vilsbøll, Jens J Holst, Asger B Lund, Mikkel B Christensen, Filip K Knop, Lærke S Gasbjerg","doi":"10.1016/S2213-8587(26)00075-6","DOIUrl":"10.1016/S2213-8587(26)00075-6","url":null,"abstract":"<p><strong>Background: </strong>The long-term glycaemic effects of glucose-dependent insulinotropic polypeptide (GIP) remain unclear. We aimed to assess whether a 6-week subcutaneous infusion of GIP alone and in combination with the GLP-1 receptor agonist semaglutide would enhance glycaemic control in individuals with type 2 diabetes.</p><p><strong>Methods: </strong>This single-centre, double-blind, parallel-group, randomised, placebo-controlled trial was conducted at the Center for Clinical Metabolic Research (Hellerup, Denmark). Inclusion criteria were age 18-74 years; a diagnosis of type 2 diabetes for at least 6 months; stable treatment; HbA<sub>1c</sub> of 6·5-10·5% (48-91 mmol/mol); and a BMI of 25-50 kg/m<sup>2</sup>. Participants were randomly assigned (1:1:1:1), using a block randomisation list, to receive either placebo plus placebo, placebo plus GIP, semaglutide plus placebo, or semaglutide plus GIP (all self-administered subcutaneously). The regimen was 8-week semaglutide or placebo run-in period (4 weeks at 0·25 mg then 4 weeks at 0·50 mg once per week), after which participants continued 0·50 mg semaglutide or placebo for an additional 6 weeks while receiving continuous subcutaneous infusions of GIP or placebo (16 pmol/kg per min). Participants and investigators were masked to treatment assignment. The primary outcome was change in 14-day mean glucose concentration assessed by continuous glucose monitoring from baseline to the end of treatment at 14 weeks, assessed in the efficacy population. This study is registered at ClinicalTrials.gov, NCT05078255 (completed).</p><p><strong>Findings: </strong>Between Jan 31, 2022, and Sept 4, 2024, we assessed 134 individuals with type 2 diabetes for eligibility, of whom 73 were ineligible. We enrolled and randomly assigned 61 participants (15 to placebo plus placebo, 16 to placebo plus GIP, 15 to semaglutide plus placebo, and 15 to semaglutide plus GIP). Ten (16%) participants discontinued the study. Participants had a median age of 64·0 years (IQR 60·0-68·0), HbA<sub>1c</sub> of 54·0 mmol/mol (49·0-60·0), diabetes duration of 6·3 years (4·2-9·8), and a mean BMI of 31·6 kg/m<sup>2</sup> (SD 4·8). 22 (36%) participants were female and 39 (64%) were male and all self-reported as White. Fasting concentrations of intact (bioactive) GIP at the end of treatment on week 14 were mean 7 pmol/L (SD 4) in the placebo plus placebo group, 45 pmol/L (43) in the placebo plus GIP group, 10 pmol/L (6) in the semaglutide plus placebo group, and 85 pmol/L (92) in the semaglutide plus GIP group; whereas fasting concentrations of total GIP were 14 pmol/L (7), 375 pmol/L (377), 18 pmol/L (19), and 527 pmol/L (338), respectively. The estimated effect of GIP on change in 14-day mean sensor-detected glucose from baseline to end of treatment was 0·80 mmol/L (97·5% CI -0·18 to 1·80; p=0·13 in the placebo plus GIP vs placebo plus placebo groups) and 0·05 mmol/L (-0·85 to 0·95; p=1·00 in the semaglutide plus GIP vs semaglu","PeriodicalId":48790,"journal":{"name":"The Lancet Diabetes & Endocrinology","volume":" ","pages":"581-593"},"PeriodicalIF":36.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148007016","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":"ADA Scientific Sessions 2026: a line crossed","authors":"Talha Burki","doi":"10.1016/s2213-8587(26)00161-0","DOIUrl":"https://doi.org/10.1016/s2213-8587(26)00161-0","url":null,"abstract":"","PeriodicalId":48790,"journal":{"name":"The Lancet Diabetes & Endocrinology","volume":"61 1","pages":""},"PeriodicalIF":44.5,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148357393","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":"Ethical eating: food choices that make a difference.","authors":"Talha Burki","doi":"10.1016/S2213-8587(26)00152-X","DOIUrl":"https://doi.org/10.1016/S2213-8587(26)00152-X","url":null,"abstract":"","PeriodicalId":48790,"journal":{"name":"The Lancet Diabetes & Endocrinology","volume":" ","pages":""},"PeriodicalIF":41.8,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148220418","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":"What is an optimal serum thyroid-stimulating hormone value in older adults?","authors":"Elizabeth N Pearce","doi":"10.1016/S2213-8587(26)00031-8","DOIUrl":"10.1016/S2213-8587(26)00031-8","url":null,"abstract":"","PeriodicalId":48790,"journal":{"name":"The Lancet Diabetes & Endocrinology","volume":" ","pages":"442-443"},"PeriodicalIF":41.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147822571","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":"Continuous glucose monitoring versus self-monitoring of blood glucose in individuals with type 2 diabetes: a randomised, multicentre, open-label, superiority trial.","authors":"Emma G Wilmot, Patrick Moore, Thozhukat Sathyapalan, Pratik Choudhary, Jonathan Z M Lim, Sankalpa Neupane, Thomas S J Crabtree, Ahmed Iqbal, Mark L Evans, Gerry Rayman, Hermione C Price, Ramzi A Ajjan, Yee S Cheah, Alistair Lumb, Samiul Mostafa, Iqbal Malik, Iain Cranston, Thinzar Min, Edward B Jude, Shivshankar Seechurn, James McLaren, Katharine Barnard-Kelly, Thomas Yates, Rachel A Elliott, Lalantha Leelarathna","doi":"10.1016/S2213-8587(26)00076-8","DOIUrl":"10.1016/S2213-8587(26)00076-8","url":null,"abstract":"<p><strong>Background: </strong>Type 2 diabetes is the most common metabolic disorder worldwide, accounting for about 90% of people living with diabetes. Glycated haemoglobin (HbA<sub>1c</sub>), a measure of chronic glycaemic exposure, correlates with the risk of long-term complications, which can result in substantial morbidity for people with diabetes and major costs to health-care systems. The value of continuous glucose monitoring (CGM) in people with type 2 diabetes managed with basal insulin and modern therapies remains unclear. FreeDM2 aimed to evaluate the effectiveness of real-time CGM in adults with type 2 diabetes.</p><p><strong>Methods: </strong>This open-label, parallel-design, randomised controlled trial conducted across 24 primary and secondary care centres in the UK enrolled adults with type 2 diabetes managed with basal insulin and SGLT2 inhibitors or GLP-1 receptor agonists or dual GIP/GLP-1 receptor agonists with HbA<sub>1c</sub> 7·5-11·0%. Participants were assigned (2:1; using permuted block randomisation by study site, generated by Sealed Envelope) to CGM (intervention) or continuation of self-monitoring of blood glucose (SMBG; control), across two phases: weeks 1-16, self-management with basal insulin self-titration; and weeks 17-32, clinician-supported where additional therapies could be initiated in line with national guidance. Participants and study site staff were not masked to group allocation. The primary outcome was difference between groups in HbA<sub>1c</sub> concentrations at 16 weeks, and the key secondary outcome was the difference between groups at 32 weeks, both in the treatment policy estimand. Safety analysis included all randomly assigned participants. The FreeDM2 randomised controlled trial is registered at ClinicalTrials.gov (NCT05944432) and is complete.</p><p><strong>Findings: </strong>Between July 26, 2023, and Jan 31, 2025, 469 individuals underwent screening for potential study inclusion, 140 were excluded due to not meeting inclusion criteria, and 329 were included in the baseline phase of the study. 26 individuals were then excluded due to insufficient data capture or withdrawal, and 303 participants were randomly assigned; 198 to the CGM intervention group and 105 to the SMBG control group. 204 (67%) participants were male and 99 (33%) were female, the mean age of the cohort was 60·7 years (SD 9·8), and mean diabetes duration was 16·7 years (6·9). Baseline HbA<sub>1c</sub> concentration was 8·8% (SD 1·0) in the CGM group and 8·8% (1·1) in the control group, decreasing to 8·0% (0·9) in the CGM group and to 8·7% (1·1) in the control group at week 16 (adjusted difference -0·6 [95% CI -0·8 to -0·3]; p<0·0001) and decreasing further to 7·8% (0·9) in the CGM group and to 8·3% (1·2) in the control group at week 32 (adjusted difference -0·5 [95% CI -0·7 to -0·2]; p<0·0001). There was a similar incidence of non-device-related adverse events in both groups, and two instances of severe hypoglycaemia in the c","PeriodicalId":48790,"journal":{"name":"The Lancet Diabetes & Endocrinology","volume":" ","pages":"463-474"},"PeriodicalIF":36.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147786503","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":"Implications of microplastics as emerging endocrine disruptors.","authors":"Stefan R Bornstein, Kaomei Guan, Torsten Wuestefeld, Saravana K Ramasamy, Yusuf Ali, Joseph J Y Sung, Charlotte Steenblock","doi":"10.1016/S2213-8587(26)00074-4","DOIUrl":"10.1016/S2213-8587(26)00074-4","url":null,"abstract":"","PeriodicalId":48790,"journal":{"name":"The Lancet Diabetes & Endocrinology","volume":" ","pages":"449"},"PeriodicalIF":41.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147718703","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":"Freedom through technology: transforming management of type 2 diabetes.","authors":"Charlotte K Boughton","doi":"10.1016/S2213-8587(26)00080-X","DOIUrl":"10.1016/S2213-8587(26)00080-X","url":null,"abstract":"","PeriodicalId":48790,"journal":{"name":"The Lancet Diabetes & Endocrinology","volume":" ","pages":"439-441"},"PeriodicalIF":41.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147786526","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":"Diabetes in sub-Saharan Africa: aligning biology, culture, and health systems for improved outcomes.","authors":"Louise M Goff, Anxious J Niwaha","doi":"10.1016/S2213-8587(26)00099-9","DOIUrl":"10.1016/S2213-8587(26)00099-9","url":null,"abstract":"","PeriodicalId":48790,"journal":{"name":"The Lancet Diabetes & Endocrinology","volume":" ","pages":"446-448"},"PeriodicalIF":41.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147786465","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":"Burden and determinants of diabetes in sub-Saharan Africa.","authors":"Charles Agyemang, John Tetteh, Maïmouna Ndour Mbaye, Roberta Lamptey, Samuel Seidu, Kamlesh Khunti, Andre-Pascal Kengne","doi":"10.1016/S2213-8587(26)00065-3","DOIUrl":"10.1016/S2213-8587(26)00065-3","url":null,"abstract":"<p><p>The prevalence of type 2 diabetes is rising rapidly across sub-Saharan Africa; however, its epidemiology, clinical phenotypes, and underlying mechanisms remain insufficiently characterised. This first paper in a Series on diabetes in sub-Saharan Africa synthesises current evidence on the burden, distribution, and determinants of diabetes, including emerging phenotypes and the roles of early life adversity, psychosocial stress, and interactions with infectious disease. We also identify major gaps in surveillance systems, research capacity, prevention, and clinical management across the region. Sub-Saharan Africa is experiencing one of the fastest global increases in diabetes, with the highest proportion of undiagnosed cases and a projected steep rise in intermediate hyperglycaemia and diabetes by 2050. Urbanisation, ageing, obesity, and lifestyle transitions are major contributors; however, a substantial proportion of type 2 diabetes occurs in lean individuals (BMI <25 kg/m²), particularly in rural settings, suggesting distinct metabolic and developmental pathways not captured by models derived from high-income countries. Bidirectional interactions between diabetes and malaria, tuberculosis, HIV, or COVID-19 make disease trajectories complex. Persistent gaps in surveillance, a reliance on modelled estimates, low genomic representation, and constrained access to modern diabetes medications hinder progress. Strengthening health system capacity, improving data infrastructure, and investing in regionally driven research are essential to develop effective, context-specific interventions and advance precision medicine tailored to sub-Saharan African populations.</p>","PeriodicalId":48790,"journal":{"name":"The Lancet Diabetes & Endocrinology","volume":" ","pages":"498-511"},"PeriodicalIF":36.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147786543","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}