Department Of Human Genetics And Molecular Medicine

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Author: search.filters.author.Singh, Paramdeep

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    Neuroimaging Genomics a Predictor of Major Depressive Disorder (MDD)
    (Springer, 2023-11-22T00:00:00) Jindal, Manav; Chhetri, Aakash; Ludhiadch, Abhilash; Singh, Paramdeep; Peer, Sameer; Singh, Jawahar; Brar, Rahatdeep Singh; Munshi, Anjana
    Depression is a complex psychiatric disorder influenced by various genetic and environmental factors. Strong evidence has established the contribution of genetic factors in depression through twin studies and the heritability rate for depression has been reported to be 37%. Genetic studies have identified genetic variations associated with an increased risk of developing depression. Imaging genetics is an integrated approach where imaging measures are combined with genetic information to explore how specific genetic variants contribute to brain abnormalities. Neuroimaging studies allow us to examine both structural and functional abnormalities in individuals with depression. This review has been designed to study the correlation of the significant genetic variants with different regions of neural activity, connectivity, and structural alteration in the brain as detected by imaging techniques to understand the scope of biomarkers in depression. This might help in developing novel therapeutic interventions targeting specific genetic pathways or brain circuits and the underlying pathophysiology of depression based on this integrated approach can be established at length. � 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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    Assessment of Resting-state functional Magnetic Resonance Imaging Connectivity Among Patients with Major Depressive Disorder: A Comparative Study
    (SAGE Publications Inc., 2023-08-29T00:00:00) Singh, Paramdeep; Singh, Jawahar; Peer, Sameer; Jindal, Manav; Khokhar, Sunil; Ludhiadch, Abhilash; Munshi, Anjana
    Background: Resting-state functional connectivity analysis has a potential to unearth the putative neuronal underpinnings of various disorders of the brain. Major depressive disorder (MDD) is regarded as a disorder arising from alterations in functional networks of the brain. Purpose: There is paucity of literature on resting-state functional magnetic resonance imaging (Rs-fMRI) in MDD, especially from the Indian subcontinent. The purpose of our study was to elucidate the differences in Rs-fMRI connectivity between MDD patients and age and gender matched healthy controls (HC). Methods: In this prospective single institute-based study, the patients were recruited consecutively based on Hamilton depression rating scale (HAM-D). Age and gender matched HC were also recruited. Rs-fMRI and anatomical MRI images were acquired for all the subjects (MDD and HC group) and subsequent analysis was done using the CONN toolbox. Results: A total of 49 subjects were included in the final analysis (MDD = 28 patients, HC = 21). HAM-D score was noted to be 24.4 � 4.8 in the MDD group. There was no significant difference between MDD and HC groups as far as age, gender, employment status, and level of education is concerned. Region-of-interest-based analysis of Rs-fMRI data showed a significantly lower connectivity between the left insula and left nucleus accumbens and between left paracingulate gyrus and bilateral posterior middle temporal gyri in MDD group as compared to HC group. Conclusion: There is reduced connectivity between certain key regions of the brain in MDD patients, that is, between the left insular cortex and the left nucleus accumbens and between the left paracingulate gyrus and the bilateral posterior middle temporal gyrus. These findings could explain the basis of clinical features of MDD such as anhedonia, rumination of thoughts, reduced visuo-spatial comprehension, reduced language function, and response to external stimuli. � 2023 Indian Academy of Neurosciences (IAN).
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    Genomic Variation Affecting MPV and PLT Count in Association with Development of Ischemic Stroke and Its Subtypes
    (Springer, 2023-07-15T00:00:00) Ludhiadch, Abhilash; Sulena; Singh, Sandeep; Chakraborty, Sudip; Sharma, Dixit; Kulharia, Mahesh; Singh, Paramdeep; Munshi, Anjana
    Platelets play a significant role in the pathophysiology of ischemic stroke since they are involved in the formation of intravascular thrombus after erosion or rupture of the atherosclerotic plaques. Platelet (PLT) count and mean platelet volume (MPV) are the two significant parameters that affect the functions of platelets. In the current study, MPV and PLT count was evaluated using flow cytometry and a cell counter. SonoClot analysis was carried out to evaluate activated clot timing (ACT), clot rate (CR), and platelet function (PF). Genotyping was carried out using GSA and Sanger sequencing, and expression analysis was performed using RT-PCR. In silico analysis was carried out using the GROMACS tool and UNAFold. The interaction of significant proteins with other proteins was predicted using the STRING database. Ninety-six genes were analyzed, and a significant association of THPO (rs6141) and ARHGEF3 (rs1354034) was observed with the disease and its subtypes. Altered genotypes were associated significantly with increased MPV, decreased PLT count, and CR. Expression analysis revealed a higher expression in patients bearing the variant genotypes of both genes. In silico analysis revealed that mutation in the THPO gene leads to the reduced compactness of protein structure. mRNA encoded by mutated ARHGEF3 gene increases the half-life of mRNA. The two significant proteins interact with many other proteins, especially the ones involved in platelet activation, aggregation, erythropoiesis, megakaryocyte maturation, and cytoskeleton rearrangements, suggesting that they could be important players in the determination of MPV values. In conclusion, the current study demonstrated the role of higher MPV affected by genetic variation in the development of IS and its subtypes. The results of the current study also indicate that higher MPV can be used as a biomarker for the disease and altered genotypes, and higher MPV can be targeted for better therapeutic outcomes. � 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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    Role of tRNA-Derived Fragments in Neurological Disorders: a Review
    (Springer, 2022-11-09T00:00:00) Mathew, Blessy Aksa; Katta, Madhumitha; Ludhiadch, Abhilash; Singh, Paramdeep; Munshi, Anjana
    tRFs are small tRNA derived fragments that are emerging as novel therapeutic targets and regulatory molecules in the pathophysiology of various neurological disorders. These are derived from precursor or mature tRNA, forming different subtypes that have been reported to be involved in neurological disorders like stroke, Alzheimer�s, epilepsy, Parkinson�s, MELAS, autism, and Huntington�s disorder. tRFs were earlier believed to be random degradation debris of tRNAs. The significant variation in the expression level of tRFs in disease conditions indicates their salient role as key players in regulation of these disorders. Various animal studies are being carried out to decipher their exact role; however, more inputs are required to transform this research knowledge into clinical application. Future investigations also call for high-throughput technologies that could help to bring out the other hidden aspects of these entities. However, studies on tRFs require further research efforts to overcome the challenges posed in quantifying tRFs, their interactions with other molecules, and the exact mechanism of function. In this review, we are abridging the current understanding of tRFs, including their biogenesis, function, relevance in clinical therapies, and potential as diagnostic and prognostic biomarkers of these neurological disorders. � 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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    Pharmacogenomics of GLP-1 receptor agonists: Focus on pharmacological profile
    (Elsevier B.V., 2022-10-28T00:00:00) Jakhar, Kalpna; Vaishnavi, Swetha; Kaur, Prabhsimran; Singh, Paramdeep; Munshi, Anjana
    Type 2 Diabetes mellitus (T2DM) is a multifactorial metabolic disorder also known as a silent killer disease. Macrovascular and microvascular complications associated with diabetes worsen the condition leading to higher comorbidity and mortality rate. Currently, available treatment strategies for diabetes include biguanides, sulfonylureas, alpha-glucosidase inhibitors, thiazolidinediones, insulin and its analogs, DPP-4 (dipeptidyl-peptidase-4) inhibitors, SGLT-2 inhibitors, and Glucagon Like Peptide-1 receptor agonists (GLP-1RAs). Synthetic agonists of GLP-1 hormone, GLP-1RAs are an emerging class of anti-diabetic drugs which target the pathophysiology of diabetes through various mechanisms and at multiple sites. They promote insulin secretion from beta cells, and the proliferation of beta cells inhibits glucagon secretion, delays gastric emptying and induces satiety. However, treatment is reported to be associated with inter-individual variations and adverse drug reactions, which are also influenced by genetic variations. There have been a few pharmacogenetic studies have been carried out on this drug class. This review discusses all the available GLP-1RAs, their pharmacokinetics, pharmacodynamics and genetic variation affecting the inter-individual variation. � 2022 Elsevier B.V.
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    Differential molecular mechanistic behavior of HDACs in cancer progression
    (Springer, 2022-08-16T00:00:00) Singh, Tashvinder; Kaur, Prabhsimran; Singh, Paramdeep; Singh, Sandeep; Munshi, Anjana
    Genetic aberration including mutation in oncogenes and tumor suppressor genes transforms normal cells into tumor cells. Epigenetic modifications work concertedly with genetic factors in controlling cancer development. Histone acetyltransferases (HATs), histone deacetylases (HDACs), DNA methyltransferases (DNMTs) and chromatin structure modifier are prospective epigenetic regulators. Specifically, HDACs are histone modifiers regulating the expression of genes implicated in cell survival, growth, apoptosis, and metabolism. The majority of HDACs are highly upregulated in cancer, whereas some have a varied function and expression in cancer progression. Distinct HDACs have a positive and negative role in controlling cancer progression. HDACs are also significantly involved in tumor cells acquiring metastatic and angiogenic potential in order to withstand the anti-tumor microenvironment. HDACs� role in modulating metabolic genes has also been associated with tumor development and survival. This review highlights and discusses the molecular mechanisms of HDACs by which they regulate cell survival, apoptosis, metastasis, invasion, stemness potential, angiogenesis, and epithelial to mesenchymal transitions (EMT) in tumor cells. HDACs are the potential target for anti-cancer drug development and various inhibitors have been developed and FDA approved for a variety of cancers. The primary HDAC inhibitors with proven anti-cancer efficacy have also been highlighted in this review. � 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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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
    (Elsevier B.V., 2023-06-23T00:00:00) 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, Ayman; 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; Bagheri, Nasser; Bagherieh, Sara; Bah, Sulaiman; Bahadory, Saeed; Bai, Ruhai; Baig, Atif Amin; Baltatu, Ovidiu Constantin; Baradaran, Hamid Reza; Barchitta, Martina; Bardhan, Mainak; Barengo, Noel C.; Barnighausen, Till Winfried; Barone, Mark Thomaz Ugliara; Barone-Adesi, Francesco; Barrow, Amadou; Bashiri, Hamideh; Basiru, Afisu; Basu, Sanjay; Basu, Saurav; Batiha, Abdul-Monim Mohammad; Batra, Kavita; Bayih, Mulat Tirfie; Bayileyegn, Nebiyou Simegnew; Behnoush, Amir Hossein; Bekele, Alehegn Bekele; Belete, Melaku Ashagrie; Belgaumi, Uzma Iqbal; Belo, Luis; Bennett, Derrick A.; Bensenor, Isabela M.; Berhe, Kidanemaryam; Berhie, Alemshet Yirga; Bhaskar, Sonu; Bhat, Ajay Nagesh; Bhatti, Jasvinder Singh; Bikbov, Boris; Bilal, Faiq; Bintoro, Bagas Suryo; Bitaraf, Saeid; Bitra, Veera R.; Bjegovic-Mikanovic, Vesna; Bodolica, Virginia; Boloor, Archith; Brauer, Michael; Brazo-Sayavera, Javier; Brenner, Hermann; Butt, Zahid A.; Calina, Daniela; Campos, Luciana Aparecida; Campos-Nonato, Ismael R.; Cao, Yin; Cao, Chao; Car, Josip; Carvalho, Marcia; Castaneda-Orjuela, Carlos A.; Catala-Lopez, Ferran; Cerin, Ester; Chadwick, Joshua; Chandrasekar, Eeshwar K.; Chanie, Gashaw Sisay; Charan, Jaykaran; Chattu, Vijay Kumar; Chauhan, Kirti; Cheema, Huzaifa Ahmad; Abebe, Endeshaw Chekol; Chen, Simiao; Cherbuin, Nicolas; Chichagi, Fatemeh; Chidambaram, Saravana Babu; Cho, William C. S.; Choudhari, Sonali Gajanan; Chowdhury, Rajiv; Chowdhury, Enayet Karim; Chu, Dinh-Toi; Chukwu, Isaac Sunday; Chung, Sheng-Chia; Coberly, Kaleb; Columbus, Alyssa; Contreras, Daniela; Cousin, Ewerton; Criqui, Michael H.; Cruz-Martins, Natalia; Cuschieri, Sarah; Dabo, Bashir; Dadras, Omid; Dai, Xiaochen; Damasceno, Albertino Antonio Moura; Dandona, Rakhi; Dandona, Lalit; Das, Saswati; Dascalu, Ana Maria; Dash, Nihar Ranjan; Dashti, Mohsen; Davila-Cervantes, Claudio Alberto; De la Cruz-Gongora, Vanessa; Debele, Gebiso Roba; Delpasand, Kourosh; Demisse, Fitsum Wolde; Demissie, Getu Debalkie; Deng, Xinlei; Denova-Gutierrez, Edgar; Deo, Salil V.; Dervi�evi?, Emina; Desai, Hardik Dineshbhai; Desale, Aragaw Tesfaw; Dessie, Anteneh Mengist; Desta, Fikreab; Dewan, Syed Masudur Rahman; Dey, Sourav; Dhama, Kuldeep; Dhimal, Meghnath; Diao, Nancy; Diaz, Daniel; Dinu, Monica; Diress, Mengistie; Djalalinia, Shirin; Doan, Linh Phuong; Dongarwar, Deepa; dos Santos Figueiredo, Francisco Winter; Duncan, Bruce B.; Dutta, Siddhartha; Dziedzic, Arkadiusz Marian; Edinur, Hisham Atan; Ekholuenetale, Michael; Ekundayo, Temitope Cyrus; Elgendy, Islam Y.; Elhadi, Muhammed; El-Huneidi, Waseem; Elmeligy, Omar Abdelsadek Abdou; Elmonem, Mohamed A.; Endeshaw, Destaw; Esayas, Hawi Leul; Eshetu, Habitu Birhan; Etaee, Farshid; Fadhil, Ibtihal; Fagbamigbe, Adeniyi Francis; Fahim, Ayesha; Falahi, Shahab; Faris, MoezAlIslam Ezzat Mahmoud; Farrokhpour, Hossein; Farzadfar, Farshad; Fatehizadeh, Ali; Fazli, Ghazal; Feng, Xiaoqi; Ferede, Tomas Y.; Fischer, Florian; Flood, David; Forouhari, Ali; Foroumadi, Roham; Koudehi, Masoumeh Foroutan; Gaidhane, Abhay Motiramji; Gaihre, Santosh; Gaipov, Abduzhappar; Galali, Yaseen; Ganesan, Balasankar; Garcia-Gordillo, M.A.; Gautam, Rupesh K.; Gebrehiwot, Mesfin; Gebrekidan, Kahsu Gebrekirstos; Gebremeskel, Teferi Gebru; Getacher, Lemma; Ghadirian, Fataneh; Ghamari, Seyyed-Hadi; Nour, Mohammad Ghasemi; Ghassemi, Fariba; Golechha, Mahaveer; Goleij, Pouya; Golinelli, Davide; Gopalani, Sameer Vali; Guadie, Habtamu Alganeh; Guan, Shi-Yang; Gudayu, Temesgen Worku; Guimaraes, Rafael Alves; Guled, Rashid Abdi; Gupta, Rajeev; Gupta, Kartik; Gupta, Veer Bala; Gupta, Vivek Kumar; Gyawali, Bishal; Haddadi, Rasool; Hadi, Najah R.; Haile, Teklehaimanot Gereziher; Hajibeygi, Ramtin; Haj-Mirzaian, Arvin; Halwani, Rabih; Hamidi, Samer; Hankey, Graeme J.; Hannan, Md Abdul; Haque, Shafiul; Harandi, Hamid; Harlianto, Netanja I.; Mahmudul Hasan, S.M.; Hasan, Syed Shahzad; Hasani, Hamidreza; Hassanipour, Soheil; Hassen, Mohammed Bheser; Haubold, Johannes; Hayat, Khezar; Heidari, Golnaz; Heidari, Mohammad; Hessami, Kamran; Hiraike, Yuta; Holla, Ramesh; Hossain, Sahadat; Hossain, Md Shakhaoat; Hosseini, Mohammad-Salar; Hosseinzadeh, Mehdi; Hosseinzadeh, Hassan; Huang, Junjie; Huda, Md Nazmul; Hussain, Salman; Huynh, Hong-Han; Hwang, Bing-Fang; Ibitoye, Segun Emmanuel; Ikeda, Nayu; Ilic, Irena M.; Ilic, Milena D.; Inbaraj, Leeberk Raja; Iqbal, Afrin; Islam, Sheikh Mohammed Shariful; Islam, Rakibul M.; Ismail, Nahlah Elkudssiah; Iso, Hiroyasu; Isola, Gaetano; Itumalla, Ramaiah; Iwagami, Masao; Iwu, Chidozie C. D.; Iyamu, Ihoghosa Osamuyi; Iyasu, Assefa N.; Jacob, Louis; Jafarzadeh, Abdollah; Jahrami, Haitham; Jain, Rajesh; Jaja, Chinwe; Jamalpoor, Zahra; Jamshidi, Elham; Janakiraman, Balamurugan; Jayanna, Krishnamurthy; Jayapal, Sathish Kumar; Jayaram, Shubha; Jayawardena, Ranil; Jebai, Rime; Jeong, Wonjeong; Jin, Yinzi; Jokar, Mohammad; Jonas, Jost B.; Joseph, Nitin; Joseph, Abel; Joshua, Charity Ehimwenma; Joukar, Farahnaz; Jozwiak, Jacek Jerzy; Kaambwa, Billingsley; Kabir, Ali; Kabthymer, Robel Hussen; Kadashetti, Vidya; Kahe, Farima; Kalhor, Rohollah; Kandel, Himal; Karanth, Shama D.; Karaye, Ibraheem M.; Karkhah, Samad; Katoto, Patrick D. M. C.; Kaur, Navjot; Kazemian, Sina; Kebede, Sewnet Adem; Khader, Yousef Saleh; Khajuria, Himanshu; Khalaji, Amirmohammad; Khan, Moien A. B.; Khan, Maseer; Khan, Ajmal; Khanal, Saval; Khatatbeh, Moawiah Mohammad; Khater, Amir M.; Khateri, Sorour; Khorashadizadeh, Fatemeh; Khubchandani, Jagdish; Kibret, Biruk Getahun; Kim, Min Seo; Kimokoti, Ruth W.; Kisa, Adnan; Kivimaki, Mika; Kolahi, Ali-Asghar; Komaki, Somayeh; Kompani, Farzad; Koohestani, Hamid Reza; Korzh, Oleksii; Kostev, Karel; Kothari, Nikhil; Koyanagi, Ai; Krishan, Kewal; Krishnamoorthy, Yuvaraj; Defo, Barthelemy Kuate; Kuddus, Mohammed; Kuddus, Md Abdul; Kumar, Rakesh; Kumar, Harish; Kundu, Satyajit; Kurniasari, Maria Dyah; Kuttikkattu, Ambily; Vecchia, Carlo La; Lallukka, Tea; Larijani, Bagher; Larsson, Anders O.; Latief, Kamaluddin; Lawal, Basira Kankia; Le, Thao Thi Thu; Le, Trang Thi Bich; Lee, Shaun Wen Huey; Lee, Munjae; Lee, Wei-Chen; Lee, Paul H.; Lee, Sang-Woong; Lee, Seung Won; Legesse, Samson Mideksa; Lenzi, Jacopo; Li, Yongze; Li, Ming-Chieh; Lim, Stephen S.; Lim, Lee-Ling; Liu, Xuefeng; Liu, Chaojie; Lo, Chun-Han; Lopes, Graciliana; Lorkowski, Stefan; Lozano, Rafael; Lucchetti, Giancarlo; Maghazachi, Azzam A.; Mahasha, Phetole Walter; Mahjoub, Soleiman; Mahmoud, Mansour Adam; Mahmoudi, Razzagh; Mahmoudimanesh, Marzieh; Mai, Anh Tuan; Majeed, Azeem; Sanaye, Pantea Majma; Makris, Konstantinos Christos; Malhotra, Kashish; Malik, Ahmad Azam; Malik, Iram; Mallhi, Tauqeer Hussain; Malta, Deborah Carvalho; Mamun, Abdullah A.; Mansouri, Borhan; Marateb, Hamid Reza; Mardi, Parham; Martini, Santi; Martorell, Miquel; Marzo, Roy Rillera; Masoudi, Reza; Masoudi, Sahar; Mathews, Elezebeth; Maugeri, Andrea; Mazzaglia, Giampiero; Mekonnen, Teferi; Meshkat, Mahboobeh; Mestrovic, Tomislav; Jonasson, Junmei Miao; Miazgowski, Tomasz; Michalek, Irmina Maria; Minh, Le Huu Nhat; Mini, G.K.; Miranda, J. Jaime; Mirfakhraie, Reza; Mirrakhimov, Erkin M.; Mirza-Aghazadeh-Attari, Mohammad; Misganaw, Awoke; Misgina, Kebede Haile; Mishra, Manish; Moazen, Babak; Mohamed, Nouh Saad; Mohammadi, Esmaeil; Mohammadi, Mohsen; Mohammadian-Hafshejani, Abdollah; Mohammadshahi, Marita; Mohseni, Alireza; Mojiri-Forushani, Hoda; Mokdad, Ali H.; Momtazmanesh, Sara; Monasta, Lorenzo; Moniruzzaman, Md; Mons, Ute; Montazeri, Fateme; Ghalibaf, AmirAli Moodi; Moradi, Yousef; Moradi, Maryam; Sarabi, Mostafa Moradi; Morovatdar, Negar; Morrison, Shane Douglas; Morze, Jakub; Mossialos, Elias; Mostafavi, Ebrahim; Mueller, Ulrich Otto; Mulita, Francesk; Mulita, Admir; Murillo-Zamora, Efren; Musa, Kamarul Imran; Mwita, Julius C.; Nagaraju, Shankar Prasad; Naghavi, Mohsen; Nainu, Firzan; Nair, Tapas Sadasivan; Najmuldeen, Hastyar Hama Rashid; Nangia, Vinay; Nargus, Shumaila; Naser, Abdallah Y.; Nassereldine, Hasan; Natto, Zuhair S.; Nauman, Javaid; Nayak, Biswa Prakash; Ndejjo, Rawlance; Negash, Hadush; Negoi, Ruxandra Irina; Nguyen, Hau Thi Hien; Nguyen, Dang H.; Nguyen, Phat Tuan; Nguyen, Van Thanh; Nguyen, Hien Quang; Niazi, Robina Khan; Nigatu, Yeshambel T.; Ningrum, Dina Nur Anggraini; Nizam, Muhammad A.; Nnyanzi, Lawrence Achilles; Noreen, Mamoona; Noubiap, Jean Jacques; Nzoputam, Ogochukwu Janet; Nzoputam, Chimezie Igwegbe; Oancea, Bogdan; Odogwu, Nkechi Martina; Odukoya, Oluwakemi Ololade; Ojha, Vivek Anand; Okati-Aliabad, Hassan; Okekunle, Akinkunmi Paul; Okonji, Osaretin Christabel; Okwute, Patrick Godwin; Olufadewa, Isaac Iyinoluwa; Onwujekwe, Obinna E.; Ordak, Michal; Ortiz, Alberto; Osuagwu, Uchechukwu Levi; Oulhaj, Abderrahim; Owolabi, Mayowa O.; Padron-Monedero, Alicia; Padubidri, Jagadish Rao; Palladino, Raffaele; Panagiotakos, Demosthenes; Panda-Jonas, Songhomitra; Pandey, Ashok; Pandey, Anamika; Pandi-Perumal, Seithikurippu R.; Stoian, Anca Mihaela Pantea; Pardhan, Shahina; Parekh, Tarang; Parekh, Utsav; Pasovic, Maja; Patel, Jay; Patel, Jenil R.; Paudel, Uttam; Pepito, Veincent Christian Filipino; Pereira, Marcos; Perico, Norberto; Perna, Simone; Petcu, Ionela-Roxana; Petermann-Rocha, Fanny Emily; Podder, Vivek; Postma, Maarten J.; Pourali, Ghazaleh; Pourtaheri, Naeimeh; Prates, Elton Junio Sady; Qadir, Mirza Muhammad Fahd; Qattea, Ibrahim; Raee, Pourya; Rafique, Ibrar; Rahimi, Mehran; Rahimifard, Mahban; Rahimi-Movaghar, Vafa; Rahman, Md Obaidur; Rahman, Muhammad Aziz; Rahman, Mohammad Hifz Ur; Rahman, Mosiur; Rahman, Md Mosfequr; Rahmani, Mohamed; Rahmani, Shayan; Rahmanian, Vahid; Rahmawaty, Setyaningrum; Rahnavard, Niloufar; Rajbhandari, Bibek; Ram, Pradhum; Ramazanu, Sheena; Rana, Juwel; Rancic, Nemanja; Ranjha, Muhammad Modassar Ali Nawaz; Rao, Chythra R.; Rapaka, Deepthi; Rasali, Drona Prakash; Rashedi, Sina; Rashedi, Vahid; Rashid, Ahmed Mustafa; Rashidi, Mohammad-Mahdi; Ratan, Zubair Ahmed; Rawaf, Salman; Rawal, Lal; Redwan, Elrashdy Moustafa Mohamed; Remuzzi, Giuseppe; Rengasamy, Kannan R. R.; Renzaho, Andre M. N.; Reyes, Luis Felipe; Rezaei, Nima; Rezaei, Nazila; Rezaeian, Mohsen; Rezazadeh, Hossein; Riahi, Seyed Mohammad; Rias, Yohanes Andy; Riaz, Muhammad; Ribeiro, Daniela; Rodrigues, Monica; Rodriguez, Jefferson Antonio Buendia; Roever, Leonardo; Rohloff, Peter; Roshandel, Gholamreza; Roustazadeh, Abazar; Rwegerera, Godfrey M.; Saad, Aly M. 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    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 risk assessment framework to estimate the risk-attributable type 2 diabetes burden for 16 risk factors falling under risk categories including environmental and occupational factors, tobacco use, high alcohol use, high body-mass index (BMI), dietary factors, and low physical activity. Using a regression framework, we forecast type 1 and type 2 diabetes prevalence through 2050 with Socio-demographic Index (SDI) and high BMI as predictors, respectively. Findings: In 2021, there were 529 million (95% uncertainty interval [UI] 500�564) people living with diabetes worldwide, and the global age-standardised total diabetes prevalence was 6�1% (5�8�6�5). At the super-region level, the highest age-standardised rates were observed in north Africa and the Middle East (9�3% [8�7�9�9]) and, at the regional level, in Oceania (12�3% [11�5�13�0]). Nationally, Qatar had the world's highest age-specific prevalence of diabetes, at 76�1% (73�1�79�5) in individuals aged 75�79 years. Total diabetes prevalence�especially among older adults�primarily reflects type 2 diabetes, which in 2021 accounted for 96�0% (95�1�96�8) of diabetes cases and 95�4% (94�9�95�9) of diabetes DALYs worldwide. In 2021, 52�2% (25�5�71�8) of global type 2 diabetes DALYs were attributable to high BMI. The contribution of high BMI to type 2 diabetes DALYs rose by 24�3% (18�5�30�4) worldwide between 1990 and 2021. By 2050, more than 1�31 billion (1�22�1�39) people are projected to have diabetes, with expected age-standardised total diabetes prevalence rates greater than 10% in two super-regions: 16�8% (16�1�17�6) in north Africa and the Middle East and 11�3% (10�8�11�9) in Latin America and Caribbean. By 2050, 89 (43�6%) of 204 countries and territories will have an age-standardised rate greater than 10%. Interpretation: Diabetes remains a substantial public health issue. Type 2 diabetes, which makes up the bulk of diabetes cases, is largely preventable and, in some cases, potentially reversible if identified and managed early in the disease course. However, all evidence indicates that diabetes prevalence is increasing worldwide, primarily due to a rise in obesity caused by multiple factors. Preventing and controlling type 2 diabetes remains an ongoing challenge. It is essential to better understand disparities in risk factor profiles and diabetes burden across populations, to inform strategies to successfully control diabetes risk factors within the context of multiple and complex drivers. Funding: Bill & Melinda Gates Foundation. � 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license