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 2022: Detection of a low grade chronic infection with live enteroviruses in the pancreas at onset of type 1 diabetes.
Publications 2022:
1. Krogvold L, Genoni A, Puggioni A, Campani D, Richardson SJ, Flaxman CS, Edwin B, Buanes T, Dahl-Jørgensen K, Toniolo A. Live enteroviruses, not other viruses, detected in human pancreas at the onset of type 1 diabetes in the DiViD-study. Diabetologia. 2022 Dec;65(12):2108-2120. doi: 10.1007/s00125-022-05779-2
2. Krogvold L, Leete P, Mynarek I, Russell MA, Gerling IC, Lenchik NI, Matthews C, Richardson SR, NL Morgan, Hanssen KF, Dahl-Jørgensen K. Detection of antiviral tissue responses and increased cell stress in the pancreatic islets of newly diagnosed T1D patients: Results from the DiViD study. Front Endocrinol (Lausanne). 2022 Jul 26;13:881997. doi: 10.3389/fendo.2022.881997
3. Välikangas T, Lietzén N, Jaakkola MK, Krogvold L, Eike MC, Kallionpää H, Tuomela S, Mathews C, Gerling IC, Oikarinen S, Hyöty H, Dahl-Jorgensen K, Elo LL, Lahesmaa R. Pancreas Whole Tissue Transcriptomics Highlights the Role of the Exocrine Pancreas in Patients With Recently Diagnosed Type 1 Diabetes. Front Endocrinol (Lausanne). 2022 Apr 13;13:861985. doi: 10.3389/fendo.2022.861985. eCollection 2022. PMID: 35498413
4. Josefsen K, Krogvold L, Gerling IC, Pociot F, Dahl-Jørgensen K, Buschard K. Development of Type 1 Diabetes may occur through a Type 2 Diabetes mechanism. Front Endocrinol (Lausanne). 2022 Dec 14;13:1032822. doi: 10.3389/fendo.2022.1032822. eCollection 2022. PMID: 36589856
5. Tekin H, Josefsen K, Krogvold L, Dahl-Jørgensen K, Gerling I, Pociot F, Buschard K. PDE12 in type 1 diabetes. Sci Rep. 2022 Oct 28;12(1):18149. doi: 10.1038/s41598-022-22890-x. PMID: 36307540
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
Ben Giepmans, Professor, University of Groningen, Netherlands
Riitta Lahesmaa, Professor, University of Turku, Finland
Matthias von Herrath, Professor, University of California La Jolla, USA
Ian Lipkin, Professor, Columbia University, New York, 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
