{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T09:15:48Z","timestamp":1791191748073,"version":"4.1.0"},"reference-count":30,"publisher":"American Diabetes Association","issue":"12","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2003,12,1]]},"abstract":"<jats:p>OBJECTIVE\u2014The aim of this study was to describe the National Institutes of Health\u2019s experience initiating an islet isolation and transplantation center, including descriptions of our first six recipients, and lessons learned.<\/jats:p>\n               <jats:p>RESEARCH DESIGN AND METHODS\u2014Six females with chronic type 1 diabetes, hypoglycemia unawareness, and no endogenous insulin secretion (undetectable serum C-peptide) were transplanted with allogenic islets procured from brain dead donors. To prevent islet rejection, patients received daclizumab, sirolimus, and tacrolimus.<\/jats:p>\n               <jats:p>RESULTS\u2014All patients noted less frequent and less severe hypoglycemia, and one-half were insulin independent at 1 year. Serum C-peptide persists in all but one patient (follow-up 17\u201322 months), indicating continued islet function. Two major procedure-related complications occurred: partial portal vein thrombosis and intra-abdominal hemorrhage. While we observed no cytomegalovirus infection or malignancy, recipients frequently developed transient mouth ulcers, diarrhea, edema, hypercholesterolemia, weight loss, myelosuppression, and other symptoms. Three patients discontinued immunosuppressive therapy: two because of intolerable toxicity (deteriorating kidney function and sirolimus-induced pneumonitis) while having evidence for continued islet function (one was insulin independent) and one because of gradually disappearing islet function.<\/jats:p>\n               <jats:p>CONCLUSIONS\u2014We established an islet isolation and transplantation program and achieved a 50% insulin-independence rate after at most two islet infusions. Our experience demonstrates that centers not previously engaged in islet transplantation can initiate a program, and our data and literature analysis support not only the promise of islet transplantation but also its remaining hurdles, which include the limited islet supply, procedure-associated complications, imperfect immunosuppressive regimens, suboptimal glycemia control, and loss of function over time.<\/jats:p>","DOI":"10.2337\/diacare.26.12.3288","type":"journal-article","created":{"date-parts":[[2007,3,5]],"date-time":"2007-03-05T22:51:27Z","timestamp":1173135087000},"page":"3288-3295","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":145,"title":["Benefits and Risks of Solitary Islet Transplantation for Type 1 Diabetes Using Steroid-Sparing Immunosuppression"],"prefix":"10.2337","volume":"26","author":[{"given":"Boaz","family":"Hirshberg","sequence":"first","affiliation":[{"name":"Transplantation and Autoimmunity Branch, National Institutes of Health\/Department of Health and Human Services, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina I.","family":"Rother","sequence":"additional","affiliation":[{"name":"Transplantation and Autoimmunity Branch, National Institutes of Health\/Department of Health and Human Services, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"Benigno J.","family":"Digon","sequence":"additional","affiliation":[{"name":"Transplantation and Autoimmunity Branch, National Institutes of Health\/Department of Health and Human Services, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet","family":"Lee","sequence":"additional","affiliation":[{"name":"Clinical Center Department of Transfusion Medicine, National Institutes of Health\/Department of Health and Human Services, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason L.","family":"Gaglia","sequence":"additional","affiliation":[{"name":"Transplantation and Autoimmunity Branch, National Institutes of Health\/Department of Health and Human Services, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Hines","sequence":"additional","affiliation":[{"name":"Clinical Center Department of Transfusion Medicine, National Institutes of Health\/Department of Health and Human Services, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth J.","family":"Read","sequence":"additional","affiliation":[{"name":"Clinical Center Department of Transfusion Medicine, National Institutes of Health\/Department of Health and Human Services, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Chang","sequence":"additional","affiliation":[{"name":"Special Procedures\u2013Diagnostic Radiology Department, National Institutes of Health\/Department of Health and Human Services, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradford J.","family":"Wood","sequence":"additional","affiliation":[{"name":"Special Procedures\u2013Diagnostic Radiology Department, National Institutes of Health\/Department of Health and Human Services, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Harlan","sequence":"additional","affiliation":[{"name":"Transplantation and Autoimmunity Branch, National Institutes of Health\/Department of Health and Human Services, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","reference":[{"key":"2022031214530662600_R1","doi-asserted-by":"crossref","unstructured":"The Diabetes Control and Complications Trial Research Group: Effect of intensive therapy on residual \u03b2-cell function in patients with type 1 diabetes in the diabetes control and complications trial: a randomized, controlled trial. Ann Intern Med\u2008128:517\u2013523, 1998","DOI":"10.7326\/0003-4819-128-7-199804010-00001"},{"key":"2022031214530662600_R2","doi-asserted-by":"crossref","unstructured":"The Diabetes Control and Complications Trial\/Epidemiology of Diabetes Interventions and Complications Research Group: Retinopathy and nephropathy in patients with type 1 diabetes four years after a trial of intensive therapy. N Engl J Med\u2008342:381\u2013389, 2000","DOI":"10.1056\/NEJM200002103420603"},{"key":"2022031214530662600_R3","doi-asserted-by":"crossref","unstructured":"Zgibor JC, Songer TJ, Kelsey SF, Weissfeld J, Drash AL, Becker D, Orchard TJ: The association of diabetes specialist care with health care practices and glycemic control in patients with type 1 diabetes: a cross-sectional analysis from the Pittsburgh epidemiology of diabetes complications study. Diabetes Care\u200823:472\u2013476, 2000","DOI":"10.2337\/diacare.23.4.472"},{"key":"2022031214530662600_R4","doi-asserted-by":"crossref","unstructured":"The Diabetes Control and Complications Trial Research Group: Hypoglycemia in the diabetes control and complications trial. Diabetes\u200846:271\u2013286, 1997","DOI":"10.2337\/diabetes.46.2.271"},{"key":"2022031214530662600_R4A","unstructured":"Venstrom JM, McBride MA, Rother KI, Hirshberg B, Orchard TJ, Harlan DM: Pancreas transplantation decreases survival for patients with diabetes and preserved kidney function. JAMA. In press"},{"key":"2022031214530662600_R5","doi-asserted-by":"crossref","unstructured":"Robertson RP, Davis C, Larsen J, Stratta R, Sutherland DE: Pancreas and islet transplantation for patients with diabetes. Diabetes Care\u200823:112\u2013116, 2000.","DOI":"10.2337\/diacare.23.1.112"},{"key":"2022031214530662600_R6","doi-asserted-by":"crossref","unstructured":"Schulak JA, Henry ML, Munda R, Mayes JT, Bohnengel A: Pancreas transplantation in Ohio: a 15-year outcomes analysis. Surgery\u2008130:546\u2013552, 2001","DOI":"10.1067\/msy.2001.116904"},{"key":"2022031214530662600_R7","doi-asserted-by":"crossref","unstructured":"Sutherland DE, Gruessner RW, Dunn DL, Matas AJ, Humar A, Kandaswamy R, Mauer SM, Kennedy WR, Goetz FC, Robertson RP, Gruessner AC, Najarian JS: Lessons learned from more than 1,000 pancreas transplants at a single institution. Ann Surg\u2008233:463\u2013501, 2001","DOI":"10.1097\/00000658-200104000-00003"},{"key":"2022031214530662600_R8","unstructured":"Ballinger WF, Lacy PE: Transplantation of intact pancreatic islets in rats. Surgery\u200872:175\u2013186, 1972"},{"key":"2022031214530662600_R9","unstructured":"Brendel M, Hering B, Schultz A, Bretzel R: International Islet Transplant Registry Report. Giessen, Germany, University of Giessen, 1999, p. 1\u201320"},{"key":"2022031214530662600_R10","doi-asserted-by":"crossref","unstructured":"Kenyon NS, Ranuncoli A, Masetti M, Chatzipetrou M, Ricordi C: Islet transplantation: present and future perspectives. Diabetes Metab Rev\u200814:303\u2013313, 1998","DOI":"10.1002\/(SICI)1099-0895(199812)14:4<303::AID-DMR243>3.0.CO;2-E"},{"key":"2022031214530662600_R11","doi-asserted-by":"crossref","unstructured":"Bretzel RG, Brandhorst D, Brandhorst H, Eckhard M, Ernst W, Friemann S, Rau W, Weimar B, Rauber K, Hering BJ, Brendel MD: Improved survival of intraportal pancreatic islet cell allografts in patients with type-1 diabetes mellitus by refined peritransplant management. J Mol Med\u200877:140\u2013143, 1999","DOI":"10.1007\/s001090050322"},{"key":"2022031214530662600_R12","doi-asserted-by":"crossref","unstructured":"Kenyon NS, Fernandez LA, Lehmann R, Masetti M, Ranuncoli A, Chatzipetrou M, Iaria G, Han D, Wagner JL, Ruiz P, Berho M, Inverardi L, Alejandro R, Mintz DH, Kirk AD, Harlan DM, Burkly LC, Ricordi C: Long-term survival and function of intrahepatic islet allografts in baboons treated with humanized anti-CD154. Diabetes\u200848:1473\u20131481, 1999","DOI":"10.2337\/diabetes.48.7.1473"},{"key":"2022031214530662600_R13","doi-asserted-by":"crossref","unstructured":"Ryan EA, Lakey JR, Rajotte RV, Korbutt GS, Kin T, Imes S, Rabinovitch A, Elliott JF, Bigam D, Kneteman NM, Warnock GL, Larsen I, Shapiro AM: Clinical outcomes and insulin secretion after islet transplantation with the Edmonton protocol. Diabetes\u200850:710\u2013719, 2001","DOI":"10.2337\/diabetes.50.4.710"},{"key":"2022031214530662600_R14","doi-asserted-by":"crossref","unstructured":"Shapiro AM, Lakey JR, Ryan EA, Korbutt GS, Toth E, Warnock GL, Kneteman NM, Rajotte RV: Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med\u2008343:230\u2013238, 2000","DOI":"10.1056\/NEJM200007273430401"},{"key":"2022031214530662600_R15","doi-asserted-by":"crossref","unstructured":"Kenyon NS, Chatzipetrou M, Masetti M, Ranuncoli A, Oliveira M, Wagner JL, Kirk AD, Harlan DM, Burkly LC, Ricordi C: Long-term survival and function of intrahepatic islet allografts in rhesus monkeys treated with humanized anti-CD154. Proc Natl Acad Sci U S A\u200896:8132\u20138137, 1999","DOI":"10.1073\/pnas.96.14.8132"},{"key":"2022031214530662600_R16","doi-asserted-by":"crossref","unstructured":"Lakey JR, Cavanagh TJ, Zieger MA, Wright M: Evaluation of a purified enzyme blend for the recovery and function of canine pancreatic islets. Cell Transplant\u20087:365\u2013372, 1998","DOI":"10.1177\/096368979800700404"},{"key":"2022031214530662600_R17","doi-asserted-by":"crossref","unstructured":"Ricordi C, Lacy PE, Finke EH, Olack BJ, Scharp DW: Automated method for isolation of human pancreatic islets. Diabetes\u200837:413\u2013420, 1988","DOI":"10.2337\/diabetes.37.4.413"},{"key":"2022031214530662600_R18","doi-asserted-by":"crossref","unstructured":"Ricordi C, Gray DW, Hering BJ, Kaufman DB, Warnock GL, Kneteman NM, Lake SP, London NJ, Socci C, Alejandro R: Islet isolation assessment in man and large animals. Acta Diabetol Lat\u200827:185\u2013195, 1990","DOI":"10.1007\/BF02581331"},{"key":"2022031214530662600_R19","doi-asserted-by":"crossref","unstructured":"Teuscher AU, Kendall DM, Smets YF, Leone JP, Sutherland DE, Robertson RP: Successful islet autotransplantation in humans: functional insulin secretory reserve as an estimate of surviving islet cell mass. Diabetes\u200847:324\u2013330, 1998","DOI":"10.2337\/diabetes.47.3.324"},{"key":"2022031214530662600_R20","doi-asserted-by":"crossref","unstructured":"Ryan EA, Lakey JR, Paty BW, Imes S, Korbutt GS, Kneteman NM, Bigam D, Rajotte RV, Shapiro AM: Successful islet transplantation: continued insulin reserve provides long-term glycemic control. Diabetes\u200851:2148\u20132157, 2002","DOI":"10.2337\/diabetes.51.7.2148"},{"key":"2022031214530662600_R21","doi-asserted-by":"crossref","unstructured":"Casey JJ, Lakey JR, Ryan EA, Paty BW, Owen R, O\u2019Kelly K, Nanji S, Rajotte RV, Korbutt GS, Bigam D, Kneteman NN, Shapiro AM: Portal venous pressure changes after sequential clinical islet transplantation. Transplantation\u200874:913\u2013915, 2002","DOI":"10.1097\/00007890-200210150-00002"},{"key":"2022031214530662600_R22","doi-asserted-by":"crossref","unstructured":"Kahan BD, Camardo JS: Rapamycin: clinical results and future opportunities. Transplantation\u200872:1181\u20131193, 2001","DOI":"10.1097\/00007890-200110150-00001"},{"key":"2022031214530662600_R23","doi-asserted-by":"crossref","unstructured":"Anyanwu AC, Rogers CA, Murday AJ: Intrathoracic organ transplantation in the United Kingdom 1995\u201399: results from the UK cardiothoracic transplant audit. Heart\u200887:449\u2013454, 2002","DOI":"10.1136\/heart.87.5.449"},{"key":"2022031214530662600_R24","doi-asserted-by":"crossref","unstructured":"Deng MC, De Meester JM, Smits JM, Heinecke J, Scheld HH: Effect of receiving a heart transplant: analysis of a national cohort entered on to a waiting list, stratified by heart failure severity: Comparative Outcome and Clinical Profiles in Transplantation (COCPIT) Study Group. BMJ\u2008321:540\u2013545, 2000","DOI":"10.1136\/bmj.321.7260.540"},{"key":"2022031214530662600_R25","doi-asserted-by":"crossref","unstructured":"Koerner MM, Durand JB, Lafuente JA, Noon GP, Torre-Amione G: Cardiac transplantation: the final therapeutic option for the treatment of heart failure. Curr Opin Cardiol\u200815:178\u2013182, 2000","DOI":"10.1097\/00001573-200005000-00010"},{"key":"2022031214530662600_R26","doi-asserted-by":"crossref","unstructured":"Rosen HR, Shackleton CR, Martin P: Indications for and timing of liver transplantation. Med Clin North Am\u200880:1069\u20131102, 1996","DOI":"10.1016\/S0025-7125(05)70480-6"},{"key":"2022031214530662600_R27","doi-asserted-by":"crossref","unstructured":"Wolfe RA, Ashby VB, Milford EL, Ojo AO, Ettenger RE, Agodoa LY, Held PJ, Port FK: Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. N Engl J Med\u2008341:1725\u20131730, 1999","DOI":"10.1056\/NEJM199912023412303"},{"key":"2022031214530662600_R28","doi-asserted-by":"crossref","unstructured":"Evans RW, Manninen DL, Garrison LP, Jr, Hart LG, Blagg CR, Gutman RA, Hull AR, Lowrie EG: The quality of life of patients with end-stage renal disease. N Engl J Med\u2008312:553\u2013559, 1985","DOI":"10.1056\/NEJM198502283120905"},{"key":"2022031214530662600_R29","doi-asserted-by":"crossref","unstructured":"Nishimura R, LaPorte RE, Dorman JS, Tajima N, Becker D, Orchard TJ: Mortality trends in type 1 diabetes: the Allegheny County (Pennsylvania) Registry 1965\u20131999. Diabetes Care\u200824:823\u2013827, 2001","DOI":"10.2337\/diacare.24.5.823"}],"container-title":["Diabetes Care"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/26\/12\/3288\/590435\/dc1203003288.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/26\/12\/3288\/590435\/dc1203003288.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,12]],"date-time":"2022-03-12T14:53:24Z","timestamp":1647096804000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/care\/article\/26\/12\/3288\/21853\/Benefits-and-Risks-of-Solitary-Islet"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,12,1]]},"references-count":30,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2003,12,1]]}},"URL":"https:\/\/doi.org\/10.2337\/diacare.26.12.3288","relation":{},"ISSN":["0149-5992","1935-5548"],"issn-type":[{"value":"0149-5992","type":"print"},{"value":"1935-5548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,12,1]]}}}