Pancreas transplantation

Dean, Patrick G.; Kukla, Aleksandra; Stegall, Mark D.; Kudva, Yogish C.

doi:10.1136/bmj.j1321

Cited by 114 publications

(94 citation statements)

References 80 publications

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“…The first successful pancreatic transplant was performed in 1966 . Standardization of surgical technique and the progressive introduction of induction T cell‐depleting agents and immunosuppressive agents has led to lower rejection rates and improved graft survival rates today .…”

Section: Pancreas and Islet Cell Transplantationmentioning

confidence: 99%

Surgical options for glycaemic control in Type 1 diabetes

2019

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In recent years, bariatric surgery, also referred to as metabolic surgery, has become the most successful treatment option in those with Type 2 diabetes and obesity. There are some similarities in the pathological pathways in Type 1 and Type 2 diabetes, but the use of surgery in Type 1 diabetes remains unestablished and controversial. The treatment and management of Type 1 diabetes can be very challenging but recent advances in surgical interventions and technology has the potential to expand and optimize treatment options. This review discusses the current status of some surgical options available to people with Type 1 diabetes. These include implantable continuous glucose monitoring systems, continuous intraperitoneal insulin infusion pumps, closed‐loop insulin delivery systems (also known as the artificial pancreas system) utilizing the latter two modalities of glucose monitoring and insulin delivery, and bariatric or metabolic surgery. Whole pancreas and islet transplantation are beyond the scope of this review but are briefly discussed.

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Section: Pancreas and Islet Cell Transplantationmentioning

confidence: 99%

Surgical options for glycaemic control in Type 1 diabetes

2019

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“…Intriguingly, it is also now possible to perform pancreas transplantation using a laparoscopic robotic approach [10]. One criticism is the lack of randomised clinical trials to establish the actual risk, benefit and cost effectiveness of pancreas transplantation [11].…”

Section: Islet Replacement Therapy: Realitymentioning

confidence: 99%

Hope vs hype: where are we in type 1 diabetes?

Skyler

2017

Diabetologia

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Much progress has been made in type 1 diabetes research. Biological replacement of islet function has been achieved with pancreas transplantation and with islet transplantation. In the future, human embryonic stem cells and/or induced pluripotent stem cells may offer a potentially unlimited source of cells for islet replacement. Another potential strategy is to induce robust beta cell replication so that regeneration of islets can be achieved. Immune interventions are being studied with the hope of arresting the type 1 diabetes disease process to either prevent the disease or help preserve beta cell function. Mechanical replacement of islet cell function involves the use of glucose sensor-controlled insulin infusion systems. As all of these avenues are pursued, headlines often overstate the case, thus hyping any given advance, which provides enormous hope for patients and families seeking a cure for type 1 diabetes. Often, however, it is an animal study or a pilot trial that is being described. The reality is that translation to successful trials in human beings may not be readily achievable. This article discusses both the hype and the hopes in type 1 diabetes research.

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“…Pancreas and islet transplantation have been demonstrated to restore long‐term normoglycaemic homeostasis for up to 5–10 years. However, donor scarcity, specialised skills and infrastructure, and strict exclusion criteria have restricted the application of such procedures to only a small number of severely diabetic patients . Moreover, substitution of daily insulin injections for lifelong immunosuppression incurs significant risks of other adverse side effects.…”

Section: Introductionmentioning

confidence: 99%

Development of a liver‐specific Tet‐off AAV8 vector for improved safety of insulin gene therapy for diabetes

Shen

Sia

et al. 2019

The Journal of Gene Medicine

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Background Diabetes mellitus is caused by a partial or complete lack of insulin production in the body. We have previously shown that a single injection of an adeno‐associated virus serotype 8 (AAV8) vector carrying a modified and codon optimized human insulin gene induced hepatic production of insulin and corrected streptozotocin (STZ)‐induced diabetes in mice for more than 1 year. Insulin production was constitutive, analogous to long‐acting insulin therapy. Methods We have developed a single AAV8 vector with a Tet‐Off regulatable system as a safety mechanism to turn off insulin secretion should hypoglycaemia develop in vector‐treated diabetic mice. We first transfected HepG2 cells or freshly isolated rat hepatocytes in vitro with the Tet‐Off system (pAAV‐Tetoff bidir ‐Alb‐luc) regulating a luciferase reporter gene. We subsequently incorporated a furin‐cleavable codon‐optimised human proinsulin cDNA into pAAV‐Tetoff bidir backbone to form the doxycycline inducible pAAV‐Tetoff bidir ‐Alb‐hINSco. Results Using STZ‐induced diabetic mice, we were able to switch off insulin secretion repeatedly with doxycycline administration, and showed full restoration of insulin secretion on withdrawing doxycycline. Conclusions The present study provides proof of concept that, under circumstances when inappropriate basal insulin secretion is a safety concern, insulin secretion from AAV8 gene therapy can be turned off reversibly with doxycycline.

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Pancreas transplantation

Cited by 114 publications

References 80 publications

Surgical options for glycaemic control in Type 1 diabetes

Surgical options for glycaemic control in Type 1 diabetes

Hope vs hype: where are we in type 1 diabetes?

Development of a liver‐specific Tet‐off AAV8 vector for improved safety of insulin gene therapy for diabetes

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