Pancreatic biopsy by minimal tail resection in live adult patients at the onset of type 1 diabetes: experiences from the DiViD study

Krogvold, Lars; Edwin, Bjørn; Buanes, Trond; Ludvigsson, Johnny; Korsgren, Olle; Hyöty, Heikki; Frisk, Gun; Hanssen, Kristian F.; Dahl‐Jørgensen, Knut

doi:10.1007/s00125-013-3155-y

Cited by 139 publications

(151 citation statements)

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“…The DiViD samples were collected by pancreatic tail resections performed 3-9 weeks after the diagnosis of T1D, and the patient characteristics have been described previously in detail (18)(19)(20)(21). Goodquality RNA, suitable for use in this present study, was possible to extract from laser-captured islets from DiViD cases 2-6.…”

Section: Human Samplesmentioning

confidence: 99%

“…When we report "overexpression" of ISGs in T1D islets, we do not know whether these genes were upregulated as a part of the pathological processes leading to T1D are a consequence of a destructive process, or even whether baseline expression levels of these genes are higher in patients in whom T1D develops. Because of the complications associated with acquiring pancreatic tissue from live patients (18), novel imaging techniques will be required to follow ongoing pathogenic processes in the pancreas over time. Nevertheless, in this study, we used the pancreatic tissue taken from subjects with recent-onset T1D in the DiViD study, which is the, so far, largest collection of wellpreserved pancreatic tissue from subjects with recent-onset T1D.…”

Section: Diabetesdiabetesjournalsorg Lundberg and Associatesmentioning

confidence: 99%

“…In this study, freshly frozen and cultured pancreatic tissue from living patients with recent-onset T1D collected within the Diabetes Virus Detection (DiViD) study (18) were examined. We have published previously that islets isolated from these patients mainly showed background levels of cytokine/chemokine release (19).…”

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Expression of Interferon-Stimulated Genes in Insulitic Pancreatic Islets of Patients Recently Diagnosed With Type 1 Diabetes

et al. 2016

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A primary insult to the pancreatic islets of Langerhans, leading to the activation of innate immunity, has been suggested as an important step in the inflammatory process in type 1 diabetes (T1D). The aim of this study was to examine whether interferon (IFN)-stimulated genes (ISGs) are overexpressed in human T1D islets affected with insulitis. By using laser capture microdissection and a quantitative PCR array, 23 of 84 examined ISGs were found to be overexpressed by at least fivefold in insulitic islets from living patients with recent-onset T1D, participating in the Diabetes Virus Detection (DiViD) study, compared with islets from organ donors without diabetes. Most of the overexpressed ISGs, including GBP1, TLR3, OAS1, EIF2AK2, HLA-E, IFI6, and STAT1, showed higher expression in the islet core compared with the peri-islet area containing the surrounding immune cells. In contrast, the T-cell attractant chemokine CXCL10 showed an almost 10-fold higher expression in the peri-islet area than in the islet, possibly partly explaining the localization of T cells mainly to this region. In conclusion, insulitic islets from recent-onset T1D subjects show overexpression of ISGs, with an expression pattern similar to that seen in islets infected with virus or exposed to IFN-γ/interleukin-1β or IFN-α.

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Section: Human Samplesmentioning

confidence: 99%

Section: Diabetesdiabetesjournalsorg Lundberg and Associatesmentioning

confidence: 99%

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Expression of Interferon-Stimulated Genes in Insulitic Pancreatic Islets of Patients Recently Diagnosed With Type 1 Diabetes

et al. 2016

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“…Knowledge voids that might be influenced by the availability of biopsy material from patients with recent-onset type 1 diabetes Armed with such curiosity and noble in purpose, Krogvold and colleagues attempted a small series of pancreatic biopsies or, more accurately, tail resections, in individuals with recentonset disease [8]. The effort was carried out as part of the Diabetes Virus Detection (DiViD) project, a collective of experts representing a wide swathe of medical disciplines, including gastroenterological surgery.…”

Section: Why Open the Box?mentioning

confidence: 99%

“…'; and perhaps for those most concerned about safety: 'Should the study have been undertaken in the first place?' An additional curious aspect of the Krogvold et al study [8] involves comparisons of its safety outcomes with those of a team of Japanese investigators some 15 years ago [9]. In the earlier study, complication rates were minimal in comparison to this modern effort, perhaps due to the Japanese study using a more traditional punch biopsy based approach, gaining small amounts of tissue with very few islets.…”

Section: Why Open the Box?mentioning

confidence: 99%

Pancreatic biopsies in type 1 diabetes: revisiting the myth of Pandora’s box

Atkinson

2014

Diabetologia

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Over a century ago, inquisitive physicians made remarkable discoveries regarding pancreatic pathology in individuals with diabetes, including those who were likely afflicted with the type 1 (autoimmune) form of the disease. Those studies of post-mortem tissues noted unique anatomical changes in islet architecture as well as the presence of unusual cellular infiltrates. In the time since, investigations of pancreatic pathology have, with near uniformity, been restricted to analysis of organs obtained post-mortem. While clearly beneficial for addressing questions of the disorder's pathogenesis, concern exists regarding potential artefacts that might occur through analysis of tissues that have been recovered hours, often many hours, following death. Beyond this, studies of tissues obtained long after the diagnosis of type 1 diabetes may not disclose important physiological events occurring at onset or even earlier in the natural history of disease, before symptomatic hyperglycaemia. To this end, Krogvold and colleagues (in this issue of Diabetologia, doi:10.1007/s00125-013-3155-y) undertook a potentially high-reward strategy involving pancreatic biopsy in living adults with recentonset type 1 diabetes. Procedures were performed under informed consent, undertaken based on recent improvements in laparoscopic techniques, and carried out by individuals with considerable surgical experience. These efforts were terminated for ethical reasons following the occurrence of serious complications (including post-operative bleeding and pancreatic leakage). The experience lends itself to analogy with the Greek myth of Pandora's box where curiosity, in terms of a desire to see what resided inside a closed container, unleashed a series of ills on humans once the container was opened. In considering the moral of that myth, one must question whether the secrets of the pancreas in those living with type 1 diabetes should, for now, remain a mystery as the process of manipulating that organ for the purpose of curiosity does not occur without harm.Keywords Biopsy . Immunology . Inflammation . Innate immunity . Pancreas . Pathology . Surgical complications . Type 1 diabetes Abbreviation DiViD Diabetes Virus Detection StudyThe myth of Pandora's boxThe myth of Pandora's box-which, for full disclosure, may more accurately be translated as 'jar'-remains one of the most oft described accounts in Greek mythology [1]. Pandora, according to the myth, was not only the first woman on Earth but also one given a variety of gifts by her god creators. Those gifts resided in a box, given to her by the gods, with the strict order never to open the box, ever. While Pandora attempted to tame her curiosity, in the end she succumbed to temptation and, after stealing keys from her husband Epimetheus, opened the box. The result was a release of all the illnesses and hardships hidden inside by the gods. Being scared, Pandora rapidly tried to close the box and, in doing so, closed hope inside.Why begin a commentary with a story thousands of years old?I...

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