Diabetes Virus Detection Study (DiViD)
DiViD started in 2009 and is the first study to provide pancreatic tissue biopsies of unique quality in 6 patients at the time of diagnosis. Of all the pancreatic islets, one third contained insulin, with several resembling completely normal islets. Inflammation in the pancreas which is typical for diabetes (called insulitis) was seen in all patients, and the immune cells were characterized in detail. Live insulin producing cells from all patients were examined in the laboratory and in some patients the insulin production improved when kept in a non-diabetic milieu. This shows a considerable reserve capacity of insulin production at the time of diagnosis. Presence of a low-grade chronic enteroviral infection in the insulin producing pancreatic islets was detected: The enterovirus capsid protein VP1 was detected in all patients and enterovirus-specific RNA sequences were detected in four of six patients (zero of six controls). New sensitive methods has detected enteroviral RNA in all six patients. The results were confirmed in various laboratories. Antiviral tissue responses were detected by various methods: Increased expression of class I HLA molecules was found in the pancreatic islets of all patients. Gene expression studies revealed increased expression of genes that handle viral infections and gave evidence of increased cellular stress, which may induce production of neo-antigens. Furthermore they detected increased interferon response and increased levels of cytokines that may contribute to cell death. Nearly twenty different international laboratories are involved using these biopsies to study the pathogenesis of type 1 diabetes. At present 39 original articles are published and frequently cited. These results is the basis for the DiViD Intervention Trial with antiviral treatment in newly diagnosed patients with type 1 diabetes.
News 2024:
Several new results from the examinations of the pancreatic biopsies have been published with regard to the etiopathogenesis of type 1 diabetes. Two studies point to impaired innate immune system which may negatively influence the antiviral defense which again may lead to the persistent, low-grade enteroviral infection of the insulin producing beta cells previously published. One study made a completely new description of the architecture of the islets of Langerhans.
Publications 2024:
Tegehall A, Ingvast S, Krogvold L, Dahl-Jørgensen K, Korsgren O. Reduced expression of central innate defense molecules in pancreatic biopsies from subjects with Type 1 diabetes. Acta Diabetol. 2024 May 8. doi: 10.1007/s00592-024-02286-1. Online ahead of print. PMID: 38717484
Buschard K, Josefsen K, Krogvold L, Gerling I, Dahl-Jørgensen K, Pociot F. Influence of sphingolipid enzymes on blood glucose levels, development of diabetes, and involvement of pericytes. Diabetes Metab Res Rev. 2024 Mar;40(3):e3792. doi: 10.1002/dmrr.3792. PMID: 38517704
Hendriks AEJ, Marcovecchio ML, Besser REJ, Bonifacio E, Casteels K, Elding Larsson H, Gemulla G, Lundgren M, Kordonouri O, Mallone R, Pociot F, Szypowska A, Toppari J, Berge TVD, Ziegler AG, Mathieu C, Achenbach P; INNODIA consortium, the Fr1da Study Group and the GPPAD Study Group.Clinical care advice for monitoring of islet autoantibody positive individuals with presymptomatic type 1 diabetes. Diabetes Metab Res Rev. 2024 Feb;40(2):e3777. doi: 10.1002/dmrr.3777. PMID: 38375753.
Verschueren van Rees N, Ashwin P, McMullan C, Krogvold L, Dahl-Jørgensen K, Morgan NG, Leete P, Wedgwood KCA. Beyond the loss of beta cells: a quantitative analysis of islet architecture in adults with and without type 1 diabetes. Diabetologia. 2025 Feb 26. doi: 10.1007/s00125-025-06376-9. Online ahead of print. PMID: 40011232
Dahl-Jørgensen K. Virus as the cause of type 1 diabetes. Trends Mol Med. 2024 Jul 13:S1471-4914(24)00183-7. doi: 10.1016/j.molmed.2024.06.011. Epub ahead of print. PMID: 39003200
Primary Investigator:
Co-investigators/participants:
Lars Krogvold, Ass. Professor, Consultant, Pediatric Dept. Oslo University Hospital
Bjørn Edwin, Professor of Surgery, Oslo University Hospital
Trond Buanes, Professor of Surgery, Oslo University Hospital
External collaborators:
Heikki Hyöty, Professor, Dept of Virology, University of Tampere, Finland
Gun Frisk, Professor, University of Uppsala, Sweden
Olle Korsgren, Professor, University of Uppsala, Sweden
Oskar Skog, Assoc. Professor, University of Uppsala, Sweden
Decio Eizirik, Professor, University of Bruxelles, Belgium
Karsten Buchard, Professor, University of Copenhagen, Denmark
Johnny Ludvigsson, Professor, Dept. of Pediatrics, University of Linköping, Sweden
Noel Morgan, Professor, University of Exeter, UK
Sara Richardsson, Assoc. Professor, University of Exeter, UK
Bart Roep, Professor, Dept. of Immunlogy, Leiden University, Netherlands
Mikael Knip, Professor, Dept. of Pediatrics, University of Helsinki, Finland
Gunilla Westermark, Professor, University of Uppsala, Sweden
Yuval Dor, Professor, University of Jerusalem, Israel
Antonio Toliono, Professor, Laboratory of Medical Microbiology, University of Varese, Italy
Riitta Lahesmaa, Professor, University of Turku, Finland
Matthias von Herrath, Professor, University of California La Jolla, USA
Ivan C. Gerling, Professor, Memphis, USA
Shiva Reddy, Professor, Auckland University, New Zealand
Malin Thulin-Flodstrøm, Professor, Karolinska Institutet, Stockholm, Sweden
Mark Peakman, Professor, Kings College, London, UK
Mark Atkinson, Professor, University of Florida, USA (nPOD)
Alberto Pugliese, Professor, University of Miami, USA (nPOD) Francesco Dotta, Professor, University of Siena, Italy