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      Single-donor islet transplantation in type 1 diabetes: patient selection and special considerations

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          Abstract

          Type 1 diabetes mellitus is an autoimmune disorder of the endocrine pancreas that currently affects millions of people in the United States. Although the disease can be managed with exogenous insulin administration, the ultimate cure for the condition lies in restoring a patient’s ability to produce their own insulin. Islet cell allotransplantation provides a means of endogenous insulin production. Though far from perfected, islet transplants are now a proven treatment for type 1 diabetics. However, proper patient selection is critical for achieving optimal outcomes. Given the shortage of transplantable organs, selecting appropriate candidates for whom the procedure will be of greatest benefit is essential. Although many of those who receive islets do not retain insulin independence, grafts do play a significant role in preventing hypoglycemic episodes that can be quite detrimental to quality of life and potentially fatal. Additionally, islet transplant requires lifelong immunosuppression. Antibodies, both preformed and following islet infusion, may play important roles in graft outcomes. Finally, no procedure is without inherent risk and islet transfusions can have serious consequences for recipients’ livers in the form of both vascular and metabolic complications. Therefore, patient-specific factors that should be taken into account before islet transplantation include aims of therapy, sensitization, and potential increased risk for hepatic and portal-venous sequelae.

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          Most cited references43

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          Long-term complications of diabetes mellitus.

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            Five-year follow-up after clinical islet transplantation.

            Islet transplantation can restore endogenous beta-cell function to subjects with type 1 diabetes. Sixty-five patients received an islet transplant in Edmonton as of 1 November 2004. Their mean age was 42.9 +/- 1.2 years, their mean duration of diabetes was 27.1 +/- 1.3 years, and 57% were women. The main indication was problematic hypoglycemia. Forty-four patients completed the islet transplant as defined by insulin independence, and three further patients received >16,000 islet equivalents (IE)/kg but remained on insulin and are deemed complete. Those who became insulin independent received a total of 799,912 +/- 30,220 IE (11,910 +/- 469 IE/kg). Five subjects became insulin independent after one transplant. Fifty-two patients had two transplants, and 11 subjects had three transplants. In the completed patients, 5-year follow-up reveals that the majority ( approximately 80%) have C-peptide present post-islet transplant, but only a minority ( approximately 10%) maintain insulin independence. The median duration of insulin independence was 15 months (interquartile range 6.2-25.5). The HbA(1c) (A1C) level was well controlled in those off insulin (6.4% [6.1-6.7]) and in those back on insulin but C-peptide positive (6.7% [5.9-7.5]) and higher in those who lost all graft function (9.0% [6.7-9.3]) (P < 0.05). Those who resumed insulin therapy did not appear more insulin resistant compared with those off insulin and required half their pretransplant daily dose of insulin but had a lower increment of C-peptide to a standard meal challenge (0.44 +/- 0.06 vs. 0.76 +/- 0.06 nmol/l, P < 0.001). The Hypoglycemic score and lability index both improved significantly posttransplant. In the 128 procedures performed, bleeding occurred in 15 and branch portal vein thrombosis in 5 subjects. Complications of immunosuppressive therapy included mouth ulcers, diarrhea, anemia, and ovarian cysts. Of the 47 completed patients, 4 required retinal laser photocoagulation or vitrectomy and 5 patients with microalbuminuria developed macroproteinuria. The need for multiple antihypertensive medications increased from 6% pretransplant to 42% posttransplant, while the use of statin therapy increased from 23 to 83% posttransplant. There was no change in the neurothesiometer scores pre- versus posttransplant. In conclusion, islet transplantation can relieve glucose instability and problems with hypoglycemia. C-peptide secretion was maintained in the majority of subjects for up to 5 years, although most reverted to using some insulin. The results, though promising, still point to the need for further progress in the availability of transplantable islets, improving islet engraftment, preserving islet function, and reducing toxic immunosuppression.
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              Type I diabetes mellitus. A chronic autoimmune disease.

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                Author and article information

                Journal
                Diabetes Metab Syndr Obes
                Diabetes Metab Syndr Obes
                Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
                Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
                Dove Medical Press
                1178-7007
                2017
                28 February 2017
                : 10
                : 73-78
                Affiliations
                Department of Surgery, Division of Transplantation, The University of Virginia Health System, Charlottesville, VA, USA
                Author notes
                Correspondence: Kenneth L Brayman, Department of Surgery, University of Virginia Health System, 1215 Lee Street, Charlottesville, VA 22908, USA, Tel +1 434 924 9370, Fax +1 434 924 5539, Email klb9r@ 123456virginia.edu
                [*]

                These authors contributed equally to this work.

                Article
                dmso-10-073
                10.2147/DMSO.S105692
                5338842
                acf3e0d4-fa7d-4bca-aa78-37b0f0bc17f0
                © 2017 Tatum et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms. php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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                Endocrinology & Diabetes
                islet transplantation,diabetes mellitus type 1,brittle diabetes,single donor,patient

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