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Ubiquitin and the DNA double-strand break repair pathway

Genome Instability & Disease 2019年第2期1卷 69-80页

作者： Somaira Nowsheen Min Deng Zhenkun Lou Mayo Clinic Medical Scientist Training Program Mayo Clinic Alix School of Medicine and Mayo Clinic Graduate School of Biomedical Sciences Mayo Clinic Rochester USA Division of Oncology Mayo Clinic Rochester USA

The ubiquitin system plays a central role in diverse cellular processes including DNA damage response. As such, it is not surprising that its dysfunction contributes to various diseases including cancer and neurodegenerative disorders. An understanding of the ubiquitin system is, therefore, important in devising treatments for such diseases. In this review, we discuss the central role of ubiquitin in DNA damage response, specifically DNA double-strand break repair. We focus on recent findings on the role of ubiquitin in the DNA double-strand break repair pathway, possible nodes of modulation, and finally their implications for treatment of various diseases.

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Extracts from Paeonia lactiflora Pallas, Rehmannia Glutinosa var. Purpurea Makino, Perilla Frutescens var. Acuta Kudo may increase the endometrial receptivity through expression of leukemia inhibitory factor and adhesion molecules

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Journal of Traditional Chinese medicine 2019年第1期39卷 15-25页

作者： Eun-Yeong Kim Tae-Wook Chung Hee-Jung Choi Yeon-Seop Jung Syng-Ook Lee Jun-Yong Choi Hyung Sik Kim Sooseong You Myeong Soo Lee Ki-Tae Ha School of Korean Medicine and Korean Medical Research Center for Healthy Aging Pusan National UniversityYangsan 50612Republic of Korea Graduate Training Program of Korean Medicine for Healthy-aging Pusan National UniversityYangsan 50612Republic of Korea Department of Food Science and Technology Keimyung UniversityDaegu 42601Republic of Korea National Clinical Research Center for Korean Medicine Korean Medicine Hospital of Pusan National UniversityYangsan 50612Republic of Korea Laboratory of Molecular Toxicology School of PharmacySungKyunKwan UniversitySuwon 16419Republic of Korea Korea Institute of Oriental Medicine Daejeon 34054Republic of Korea

OBJECTIVE: To find out the combination of the extracts from Paeonia lactiflora Pallas(PL), Rehmannia Glutinosa var. Purpurea Makino(RG), Perilla Frutescens var. Acuta Kudo(PF) to increase endometrial ***: Herbal medicines were extracted with boiling water and polysaccharides were *** examined the effect of PL, RG, and PF(PRP), a most effective herbal formula deduced from constitutive ingredient herbs of Antai Yin which is composed of PRP, on the leukemia inhibitory factor(LIF) expression and endometrial ***: The combination of the extracts from PRP induced the LIF expression in Ishikawa cells and increased the adhesion between Ishikawa and JAr cells. In addition, PRP-induced attachment of JAr cells onto Ishikawa cells and expression of adhesion molecules, ITGAV, ITGB5, CD44 s, and Lselectin, are significantly reduced by knock-down of LIF ***: Induced by the combination of the PRP extracts, the adhesion between trophoblast and endometrial cells are mediated by expression of LIF and adhesion molecules. Thus, we suggest the combination of the PRP extracts may be a novel therapy for enhancing embryo implantation rate.

关键词： Paeonia Rehmannia Perilla Embryo implantation Endometrium Leukemia inhibitory factor Cell adhesion molecules

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Lysosomal dysfunction and inflammatory sterol metabolism in pulmonary arterial hypertension

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Science (New York, N.Y.) 2025年第6732期387卷 eadn7277页

作者： Harvey, Lloyd D. Alotaibi, Mona Tai, Yi-Yin Tang, Ying Kim, Hee-Jung J Kelly, Neil J. Sun, Wei Woodcock, Chen-Shan C Arshad, Sanya Culley, Miranda K. El Khoury, Wadih Xie, Rong Al Aaraj, Yassmin Zhao, Jingsi Hafeez, Neha Rao, Rashmi J. Jiang, Siyi Negi, Vinny Kirillova, Anna Perk, Dror Watson, Annie M. St Croix, Claudette M. Stolz, Donna B. Lee, Ji Young Cheng, Mary Hongying Zhang, Manling Detmer, Samuel Guzman, Edward Manan, Rajith S. Saggar, Rajan Haley, Kathleen J. Waxman, Aaron B. Okawa, Satoshi Schwantes-An, Tae-Hwi Pauciulo, Michael W. Wang, Bing Webb, Amy Chauvet, Caroline Anderson, Daniel G. Nichols, William C. Desai, Ankit A. Lafyatis, Robert Nouraie, S Mehdi Wu, Haodi McDonald, Jeffrey G. Cheng, Susan Bahar, Ivet Bertero, Thomas Benza, Raymond L. Jain, Mohit Chan, Stephen Y. Medical Scientist Training Program University of Pittsburgh Pittsburgh PA United States Center for Pulmonary Vascular Biology and Medicine Heart Lung Blood Vascular Medicine Institute University of Pittsburgh Pittsburgh PA United States Division of Cardiology University of Pittsburgh School of Medicine Pittsburgh PA United States Division of Pulmonary and Critical Care Medicine University of California San Diego La Jolla CA United States Department of Medicine University of California La Jolla San Diego CA United States Department of Pharmacology University of California La Jolla San Diego CA United States Division of Cardiology Veterans Affairs Pittsburgh Healthcare System Pittsburgh PA United States Center for Biologic Imaging University of Pittsburgh Pittsburgh PA United States Laufer Center for Physical and Quantitative Biology Stony Brook University Stony Brook NY United States Department of Biochemistry and Cell Biology Stony Brook University Stony Brook NY United States Department of Chemistry Massachusetts Institute of Technology Boston MA United States Institute of Medical Engineering and Science Massachusetts Institute of Technology Boston MA United States School of Engineering and Applied Sciences Harvard University Cambridge MA United States Department of Chemical Engineering Massachusetts Institute of Technology Boston MA United States Department of Medicine David Geffen School of Medicine University of California Los Angeles (UCLA) Los Angeles CA USA Department of Pathology David Geffen School of Medicine UCLA Los Angeles CA United States Division of Pulmonary and Critical Care Medicine Department of Medicine Brigham and Women's Hospital Harvard Medical School Boston MA United States Department of Computational and Systems Biology University of Pittsburgh Pittsburgh PA United States McGowan Institute for Regenerative Medicine University of Pittsburgh Pittsburgh PA United States Department of Medical and Molecular G

Vascular inflammation regulates endothelial pathophenotypes, particularly in pulmonary arterial hypertension (PAH). Dysregulated lysosomal activity and cholesterol metabolism activate pathogenic inflammation, but their relevance to PAH is unclear. Nuclear receptor coactivator 7 (NCOA7) deficiency in endothelium produced an oxysterol and bile acid signature through lysosomal dysregulation, promoting endothelial pathophenotypes. This oxysterol signature overlapped with a plasma metabolite signature associated with human PAH mortality. Mice deficient for endothelial Ncoa7 or exposed to an inflammatory bile acid developed worsened PAH. Genetic predisposition to NCOA7 deficiency was driven by single-nucleotide polymorphism rs11154337, which alters endothelial immunoactivation and is associated with human PAH mortality. An NCOA7-activating agent reversed endothelial immunoactivation and rodent PAH. Thus, we established a genetic and metabolic paradigm that links lysosomal biology and oxysterol processes to endothelial inflammation and PAH.

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Structural and Biophysical Analysis of the Calcium-Activated Chloride Channel Regulator 1 (CLCA1) VWA Domain Suggests Mode of TMEM16A Engagement

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SSRN 2019年

作者： Berry, Kayla N. Brett, Tom J. Immunology Program and Medical Scientist Training Program Department of Internal Medicine Division of Pulmonary and Critical Care Department of Cell Biology and Physiology Department of Biochemistry and Molecular Biophysics Washington University School of Medicine St. LouisMO63110 United States

The secreted protein calcium-activated chloride channel regulator 1 (CLCA1) utilizes a von Willebrand Factor type A domain (VWA) to bind to and potentiate the calcium activated chloride channel TMEM16A. To gain insight into this unique potentiation mechanism, we determined the 2.0 Å crystal structure of human CLCA1 VWA bound to Ca2+, the first CLCA family structure reported. The structure reveals the metal ion dependent adhesion site (MIDAS) in a high-affinity "open" conformation, engaging in crystal contacts that likely mimic how CLCA1 engages TMEM16A. The CLCA1 VWA contains a disulfide bond between α3 and α4 in close proximity to the MIDAS that is invariant in the CLCA family and unique in VWA structures. Further biophysical studies indicate that CLCA1 VWA is preferably stabilized by Mg2+ over Ca2+ and that a6 atypically extends from the VWA core. Finally, an analysis of TMEM16A structures suggests residues likely to mediate interaction with CLCA1 VWA. © 2019, The Authors. All rights reserved.

关键词： Glycoproteins

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DIPG-58. Therapeutic HDAC targeting in hypermutant CNS tumors

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Neuro-Oncology 2022年第SUPPLEMENT_1期24卷 i32-i32页

作者： Myers, Carrie Noll, Alyssa Biery, Matthew Meechan, Michael Tahiri, Sophie Foster, Jessica Dun, Matthew Olson, James Vitanza, Nicholas The Ben Towne Center for Childhood Cancer Research Seattle Children’s Research Institute Seattle WA USA Molecular and Cellular Biology Graduate Program and Medical Scientist Training Program University of Washington Seattle Washington USA Division of Oncology The Children's Hospital of Philadelphia Philadelphia PA USA Department of Pediatrics Perelman School of Medicine University of Pennsylvania Philadelphia PA USA Cancer Signaling Research Group School of Biomedical Sciences and Pharmacy College of Health Medicine and Wellbeing University of Newcastle Callaghan NSW Australia Individualised Medicine Program Hunter Medical Research Institute New Lambton Heights NSW Australia Division of Pediatric Hematology Oncology Bone Marrow Transplant and Cellular Therapy Department of Pediatrics Seattle Children’s Hospital University of Washington Seattle WA USA

Diffuse intrinsic pontine glioma (DIPG) is a universally fatal tumor of the pons, most often characterized by mutations in genes encoding histone 3, that led to the classification diffuse midline glioma, H3 K27M-mutant (DMG). However, 15% of DIPG are histone wildtype (H3WT) and can have a hypermutant phenotype, characterized by mutations in DNA mismatch repair that also occur in pediatric high-grade glioma (pHGG). We previously published the preclinical efficacy of quisinostat in DMG. As hypermutant CNS tumors share transcriptional disruption with DMG, we investigated if HDAC inhibition was also therapeutic against hypermutant DIPG and pHGG. We tested PBT-24, a PMS2 mutant, treatment-naïve, patient-derived hypermutant DIPG model, and found similar quisinostat sensitivity compared to other DMG cultures in vitro (IC50 = ~30 nM), as well as significant efficacy in a xenograft flank model (60 day mean tumor size of 1109mm3 [vehicle] vs. 19mm3 [quisinostat-treated]). This in vivo effect was greater than the anti-tumor effect observed in a xenograft flank non-hypermutant DMG model PBT-09 (60 day mean tumor size of 1006mm3 [vehicle] vs. 244mm3 [quisinostat-treated]). To validate the effect of hypermutation on sensitivity to quisinostat, we generated PMS2 knock-out (KO) and MSH2 KO isogenic cell lines using the H3WT model VUMC-DIPG-10. In a xenograft flank model, we observed increased quisinostat sensitivity in the KO models (20 day mean tumor volume of 547mm3 [parental], 396mm3 [PMS2 KO], and 150mm3 [MSH2 KO]). RNA sequencing of quisinostat-treated PBT-24 revealed an increase in acute inflammatory response genes which we are investigating as a mechanism of action for HDACi against hypermutant tumors. Ultimately, we demonstrate the in vivo efficacy of quisinostat against hypermutant DIPG that supports the investigation of HDAC inhibition as a treatment strategy across hypermutant CNS tumors.

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Publisher Correction: Multistate and functional protein design using RoseTTAFold sequence space diffusion

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Nature biotechnology 2024年 2024 Oct 7页

作者： Sidney Lyayuga Lisanza Jacob Merle Gershon Samuel W K Tipps Jeremiah Nelson Sims Lucas Arnoldt Samuel J Hendel Miriam K Simma Ge Liu Muna Yase Hongwei Wu Claire D Tharp Xinting Li Alex Kang Evans Brackenbrough Asim K Bera Stacey Gerben Bruce J Wittmann Andrew C McShan David Baker Department of Biochemistry University of Washington Seattle WA USA. Institute for Protein Design University of Washington Seattle WA USA. Graduate Program in Biological Physics Structure and Design University of Washington Seattle WA USA. Department of Molecular Engineering University of Washington Seattle WA USA. Molecular & Cellular Biology Medical Scientist Training Program University of Washington Seattle WA USA. Faculty of Engineering Sciences Heidelberg University Heidelberg Germany. School of Chemistry and Biochemistry Georgia Institute of Technology Atlanta GA USA. Office of the Chief Scientific Officer Microsoft Redmond WA USA. Department of Biochemistry University of Washington Seattle WA USA. dabaker@uw.edu. Institute for Protein Design University of Washington Seattle WA USA. dabaker@uw.edu. Howard Hughes Medical Institute University of Washington Seattle WA USA. dabaker@uw.edu.

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The Clinical and Electrocardiographic Phenotype of Patients with Genotype Negative Long QT Syndrome

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Heart rhythm 2025年

作者： Vanessa Karlinski Vizentin Raquel Neves Sahej Bains Iuri Ferreira Felix David J Tester J Martijn Bos John R Giudicessi Michael J Ackerman Department of Molecular Pharmacology & Experimental Therapeutics (Windland Smith Rice Sudden Death Genomics Laboratory) Mayo Clinic Rochester MN. Department of Molecular Pharmacology & Experimental Therapeutics (Windland Smith Rice Sudden Death Genomics Laboratory) Mayo Clinic Rochester MN Medical Scientist Training Program Mayo Clinic Rochester MN. Deparment of Internal Medicine Mayo Clinic Rochester MN. Department of Cardiovascular Medicine (Divisions of Heart Rhythm Services and Circulatory Failure Windland Smith Rice Genetic Heart Rhythm Clinic) Mayo Clinic Rochester MN. Department of Cardiovascular Medicine (Divisions of Heart Rhythm Services and Circulatory Failure Windland Smith Rice Genetic Heart Rhythm Clinic) Mayo Clinic Rochester MN Department of Pediatric and Adolescent Medicine (Division of Pediatric Cardiology) Mayo Clinic Rochester MN. Electronic address: ackerman.michael@mayo.edu.

BACKGROUND:Long QT syndrome (LQTS) is a genetic heart disease that increases the risk for ventricular arrhythmias and sudden cardia arrest. Despite advances in genetic testing, a small subset of LQTS patients remain genetically elusive. OBJECTIVE:To determine the prevalence and clinical characteristics of patients with a phenotype of LQTS but genotype negative. METHODS:This study aimed to identify phenotype-positive, genotype-negative LQTS patients seen at Mayo Clinic (2000 - 2024). Retrospective data included demographics, clinical evaluations, ECGs, and genetic results. Diagnosis adhered to established criteria, and genotype-negative LQTS was defined by the absence of pathogenic variants despite clinical presentation. RESULTS:The study included 1,829 patients with LQTS. From these, 1,706 (93%) had pathogenic or likely pathogenic variants and 95 patients (5%) had upgraded clinically variants of uncertain significance, leaving 32 (1.7%) with negative genetic tests. Among the genotype-negative patients, 17 underwent next-generation sequencing, identifying a genetic cause in 6 cases (0.3% of the total). The mean age at diagnosis for the remaining 26 patients was 25 ± 15 years, 76% being female and an average initial QTc of 498 ± 41 ms. Fourteen patients (53%) experienced cardiac events prior to diagnosis, and 11 (44%) received an implantable cardioverter-defibrillator (ICD). The mean follow-up period was 8 ± 7 years. CONCLUSION:Genotype-negative LQTS accounted for <2% of our cohort, highlighting diagnostic and management challenges. Comprehensive clinical evaluation and advanced genetic testing remain essential for accurate diagnosis and care.

关键词： Genetic Heart Disease Genotype Negative Long QT syndrome Next Generation Sequencing Sudden Cardiac Death

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HMGA2 and protein leucine methylation drive pancreatic cancer lineage plasticity

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Nature Communications 2025年第1期16卷 1-17页

作者： Dobersch, Stephanie Yamamoto, Naomi Schutter, Aidan Cavender, Sarah M. Robertson, Tess M. Kartha, Nithya Samraj, Annie N. Doron, Ben Poole, Lisa A. Wladyka, Cynthia L. Zhang, Amy Jang, Gun Ho Mahalingam, Aswanth H. Barreto, Guillermo Raghavan, Srivatsan Narla, Goutham Notta, Faiyaz Eisenman, Robert N. Hsieh, Andrew C. Kugel, Sita Human Biology Division Fred Hutchinson Cancer Center Seattle WA United States Medical Scientist Training Program University of Washington Seattle WA United States Molecular & Cellular Biology Graduate Program University of Washington Seattle WA United States Division of Transfusion Medicine Department of Laboratory Medicine University of Washington School of Medicine Seattle WA United States PanCuRx Translational Research Initiative Ontario Institute for Cancer Research Toronto ON Canada Department of Medical Oncology Dana-Farber Cancer Institute Boston MA United States Université de Lorraine CNRS Laboratoire IMoPA Nancy France Lung Cancer Epigenetic Max-Planck-Institute for Heart and Lung Research Bad Nauheim Germany Broad Institute of MIT and Harvard Cambridge MA United States Harvard Medical School Boston MA United States Department of Medicine Brigham and Women’s Hospital Boston MA United States Division of Genetic Medicine Department of Internal Medicine University of Michigan Ann Arbor MI United States Rogel Cancer Center University of Michigan Ann Arbor MI United States Princess Margaret Cancer Centre University Health Network Toronto ON Canada Department of Medical Biophysics University of Toronto Toronto ON Canada Basic Sciences Division Fred Hutchinson Cancer Center Seattle WA United States Department of Medicine University of Washington Seattle WA United States Department of Genome Sciences University of Washington Seattle WA United States

Basal pancreatic ductal adenocarcinoma (PDAC) has the worst overall survival and is the only subtype that serves as an independent poor prognostic factor. We identify elevated levels of LIN28B and its downstream target, HMGA2, in basal PDAC. Notably, LIN28B significantly accelerates KRAS-driven PDAC progression in a mouse model. Here, we show that HMGA2 promotes basal PDAC pathogenesis by enhancing mRNA translation downstream of LIN28B. Mechanistically, HMGA2 suppresses leucine carboxyl methyltransferase 1 (LCMT1) at the chromatin level, reducing PP2A methylation and activity. This leads to increased phosphorylation of S6K and eIF4B, boosting mRNA translation. Additionally, HMGA2 downregulates B56α (PPP2R5A), disrupting functional PP2A holoenzyme assembly and further sustaining phosphorylated S6K levels. Impaired PP2A function mimics HMGA2’s effects, reinforcing increased mRNA translation and basal lineage features. This work uncovers a critical link between the LIN28B/HMGA2 axis, protein synthesis, and PDAC lineage specificity via LCMT1-mediated PP2A methylation and B56α-PP2A disruption. © The Author(s) 2025.

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A syndromic neurodevelopmental disorder caused by rare variants in PPFIA3 (vol 111, pg 96, 2024)

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AMERICAN JOURNAL OF HUMAN GENETICS 2024年第4期11卷 805-805页

作者： Paul, Maimuna S. Michener, Sydney L. Pan, Hongling Chan, Hiuling Pfliger, Jessica M. Rosenfeld, Jill A. Lerma, Vanesa C. Tran, Alyssa Longley, Megan A. Lewis, Richard A. Weisz-Hubshman, Monika Bekheirnia, Mir Reza Bekheirnia, Nasim Massingham, Lauren Zech, Michael Wagner, Matias Engels, Hartmut Cremer, Kirsten Mangold, Elisabeth Peters, Sophia Trautmann, Jessica Perne, Claudia Mester, Jessica L. Sacoto, Maria J. Guillen Person, Richard McDonnell, Pamela P. Cohen, Stacey R. Lusk, Laina Cohen, Ana S. A. Le Pichon, Jean-Baptiste Pastinen, Tomi Zhou, Dihong Engleman, Kendra Racine, Caroline Faivre, Laurence Moutton, Sebastien Denomme-Pichon, Anne-Sophie Koh, Hyun Yong Poduri, Annapurna Bolton, Jeffrey Knopp, Cordula Suh, Dong Sun Julia Maier, Andrea Toosi, Mehran Beiraghi Karimiani, Ehsan Ghayoor Maroofian, Reza Schaefer, Gerald Bradley Ramakumaran, Vijayalakshmi Vasudevan, Pradeep Banos-Pinero, Benito Pagnamenta, Alistair T. Prasad, Chitra Osmond, Matthew Schuhmann, Sarah Vasileiou, Georgia Russ-Hall, Sophie Scheffer, Ingrid E. Carvill, Gemma L. Mefford, Heather Bacino, Carlos A. Lee, Brendan H. Chao, Hsiao-Tuan Department of Pediatrics Section of Neurology and Developmental Neuroscience Baylor College of Medicine Houston TX USA Jan and Dan Duncan Neurological Research Institute Texas Children’s Hospital Houston TX USA Cain Pediatric Neurology Research Foundation Laboratories Jan and Dan Duncan Neurological Research Institute Houston TX USA Department of Molecular and Human Genetics Baylor College of Medicine Houston TX USA Augustana College Rock Island IL USA Summer Undergraduate Research Training (SMART) Program Baylor College of Medicine Houston TX USA Graduate Program in Electrical and Computer Engineering Rice University Houston TX USA Department of Psychology University of Houston Houston TX USA Department of Ophthalmology Baylor College of Medicine Houston TX USA Renal Genetics Clinic Baylor College of Medicine Houston TX USA Rhode Island Hospital and Hasbro Children’s Hospital Providence RI USA Institute of Neurogenomics Helmholtz Zentrum München Munich Germany Institute of Human Genetics School of Medicine Technical University Munich Germany Institute for Advanced Study Technical University of Munich Garching Germany Division of Pediatric Neurology Developmental Neurology and Social Pediatrics Dr. von Hauner Children’s Hospital Munich Germany Institute of Human Genetics School of Medicine University Hospital Bonn University of Bonn Bonn Germany GeneDx Gaithersburg MD USA Epilepsy NeuroGenetics Initiative (ENGIN) Division of Neurology Children’s Hospital of Philadelphia Philadelphia PA USA Department of Neurology Perelman School of Medicine University of Pennsylvania Philadelphia PA USA Children’s Mercy Kansas City Genomic Medicine Center The University of Missouri-Kansas City (UMKC) School of Medicine Kansas City MO USA Department of Pediatrics Children’s Mercy Kansas City Kansas City MO USA Children’s Mercy Research Institute Kansas City MO USA Children’s Mercy Hospital Kansas City MO USA University Hospital Dijon Franc

PPFIA3 encodes the protein-tyrosine phosphatase, receptor-type, F-polypeptide-interacting-protein-alpha-3 (PPFIA3), which is a member of the LAR-protein-tyrosine phosphatase-interacting-protein (liprin) family involved in synapse formation and function, synaptic vesicle transport, and presynaptic active zone assembly. The protein structure and function are evolutionarily well conserved, but human diseases related to PPFIA3 dysfunction are not yet reported in OMIM. Here, we report 20 individuals with rare PPFIA3 variants (19 heterozygous and 1 compound heterozygous) presenting with developmental delay, intellectual disability, hypotonia, dysmorphisms, microcephaly or macrocephaly, autistic features, and epilepsy with reduced penetrance. Seventeen unique PPFIA3 variants were detected in 18 families. To determine the pathogenicity of PPFIA3 variants in vivo, we generated transgenic fruit flies producing either human wild-type (WT) PPFIA3 or five missense variants using GAL4-UAS targeted gene expression systems. In the fly overexpression assays, we found that the PPFIA3 variants in the region encoding the N-terminal coiled-coil domain exhibited stronger phenotypes compared to those affecting the C-terminal region. In the loss-of-function fly assay, we show that the homozygous loss of fly Liprin-α leads to embryonic lethality. This lethality is partially rescued by the expression of human PPFIA3 WT, suggesting human PPFIA3 function is partially conserved in the fly. However, two of the tested variants failed to rescue the lethality at the larval stage and one variant failed to rescue lethality at the adult stage. Altogether, the human and fruit fly data reveal that the rare PPFIA3 variants are dominant-negative loss-of-function alleles that perturb multiple developmental processes and synapse formation.

关键词： neurodevelopmental disorder synaptic protein active zone protein Mendelian phenotypes fruit flies

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Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021

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The Lancet 2023年第10397期402卷 203-234页

作者： Ong, Kanyin Liane Stafford, Lauryn K. McLaughlin, Susan A. Boyko, Edward J. Vollset, Stein Emil Smith, Amanda E. Dalton, Bronte E. Duprey, Joe Cruz, Jessica A. Hagins, Hailey Lindstedt, Paulina A. Aali, Amirali Abate, Yohannes Habtegiorgis Abate, Melsew Dagne Abbasian, Mohammadreza Abbasi-Kangevari, Zeinab Abbasi-Kangevari, Mohsen ElHafeez, Samar Abd Abd-Rabu, Rami Abdulah, Deldar Morad Abdullah, Abu Yousuf Md Abedi, Vida Abidi, Hassan Aboagye, Richard Gyan Abolhassani, Hassan Abu-Gharbieh, Eman Abu-Zaid, Ahmed Adane, Tigist Demssew Adane, Denberu Eshetie Addo, Isaac Yeboah Adegboye, Oyelola A. Adekanmbi, Victor Adepoju, Abiola Victor Adnani, Qorinah Estiningtyas Sakilah Afolabi, Rotimi Felix Agarwal, Gina Aghdam, Zahra Babaei Agudelo-Botero, Marcela Arriagada, Constanza Elizabeth Aguilera Agyemang-Duah, Williams Ahinkorah, Bright Opoku Ahmad, Danish Ahmad, Rizwan Ahmad, Sajjad Ahmad, Aqeel Ahmadi, Ali Ahmadi, Keivan Ahmed, Ali Ahmed, Luai A. Ahmed, Syed Anees Ajami, Marjan Akinyemi, Rufus Olusola Al Hamad, Hanadi Al Hasan, Syed Mahfuz AL-Ahdal, Tareq Mohammed Ali Alalwan, Tariq A. Al-Aly, Ziyad AlBataineh, Mohammad T. Alcalde-Rabanal, Jacqueline Elizabeth Alemi, Sharifullah Ali, Hassam Alinia, Tahereh Aljunid, Syed Mohamed Almustanyir, Sami Al-Raddadi, Rajaa M. Alvis-Guzman, Nelson Amare, Firehiwot Ameyaw, Edward Kwabena Amiri, Sohrab Amusa, Ganiyu Adeniyi Andrei, Catalina Liliana Anjana, Ranjit Mohan Ansar, Adnan Ansari, Golnoosh Ansari-Moghaddam, Alireza Anyasodor, Anayochukwu Edward Arabloo, Jalal Aravkin, Aleksandr Y. Areda, Demelash Arifin, Hidayat Arkew, Mesay Armocida, Benedetta Arnlov, Johan Artamonov, Anton A. Arulappan, Judie Aruleba, Raphael Taiwo Arumugam, Ashokan Aryan, Zahra Asemu, Mulu Tiruneh Asghari-Jafarabadi, Mohammad Askari, Elaheh Asmelash, Daniel Astell-Burt, Thomas Athar, Mohammad Athari, Seyyed Shamsadin Atout, Maha Moh'd Wahbi Avila-Burgos, Leticia Awaisu, Ahmed Azadnajafabad, Sina Darshan, B.B. Babamohamadi, Hassan Badar, Muhammad Badawi, Alaa Badiye, Ashish D. Baghcheghi, Nayereh Baghe Institute for Health Metrics and Evaluation School of Medicine General Medicine Service Department of Veterans Affairs Seattle WA United States Department of Health Metrics Sciences School of Medicine Faculty of Medicine France Department of Clinical Governance and Quality Improvement Aleta Wondo Hospital Aleta Wondo Ethiopia Department of Nursing Woldia University Woldia Ethiopia Department of Nursing Department of Orthopedic Surgery Orthopaedic Surgery Social Determinants of Health Research Center Non-communicable Diseases Research Center Epidemiology Department Evidence-Based Practice Center Community and Maternity Nursing Unit University of Duhok Duhok Iraq School of Planning Faculty of Environment Department of Public Health Sciences Penn State College of Medicine Pennsylvania State University Hershey PA United States Biocomplexity Institute Virginia Tech Blacksburg VA United States College of Medicine Department of Public Health Laboratory Technology Sciences Department Department of Family and Community Health University of Health and Allied Sciences Ho Ghana Research Center for Immunodeficiencies Department of Biosciences and Nutrition Karolinska University Hospital Huddinge Sweden Clinical Sciences Department Department of Surgery Department of Surgery Department of Obstetrics & Gynecology College of Graduate Health Sciences University of Tennessee Memphis TN United States Department of Obstetrics & Gynecology Department of Clinical and Psychosocial Epidemiology Department of Anesthesia and Critical Care Centre for Social Research in Health Quality and Systems Performance Unit Cancer Institute NSW Sydney NSW Australia Department of Public Health and Tropical Medicine HIV and Infectious Diseases Department Jhpiego Abuja Nigeria Adolescent Research and Care Department Adolescent Friendly Research Initiative and Care Ado Ekiti Nigeria Department of Epidemiology Department of Epidemiology and Medical Statistics Department of Family Medicine McMaster University

Background: Diabetes is one of the leading causes of death and disability worldwide, and affects people regardless of country, age group, or sex. Using the most recent evidentiary and analytical framework from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD), we produced location-specific, age-specific, and sex-specific estimates of diabetes prevalence and burden from 1990 to 2021, the proportion of type 1 and type 2 diabetes in 2021, the proportion of the type 2 diabetes burden attributable to selected risk factors, and projections of diabetes prevalence through 2050. Methods: Estimates of diabetes prevalence and burden were computed in 204 countries and territories, across 25 age groups, for males and females separately and combined;these estimates comprised lost years of healthy life, measured in disability-adjusted life-years (DALYs;defined as the sum of years of life lost [YLLs] and years lived with disability [YLDs]). We used the Cause of Death Ensemble model (CODEm) approach to estimate deaths due to diabetes, incorporating 25 666 location-years of data from vital registration and verbal autopsy reports in separate total (including both type 1 and type 2 diabetes) and type-specific models. Other forms of diabetes, including gestational and monogenic diabetes, were not explicitly modelled. Total and type 1 diabetes prevalence was estimated by use of a Bayesian meta-regression modelling tool, DisMod-MR 2.1, to analyse 1527 location-years of data from the scientific literature, survey microdata, and insurance claims;type 2 diabetes estimates were computed by subtracting type 1 diabetes from total estimates. Mortality and prevalence estimates, along with standard life expectancy and disability weights, were used to calculate YLLs, YLDs, and DALYs. When appropriate, we extrapolated estimates to a hypothetical population with a standardised age structure to allow comparison in populations with different age structures. We used the comparative r

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