title: Benefits and risks of solitary islet transplantation for type 1 diabetes using steroid-sparing immunosuppression: the National Institutes of Health experience.
abstract: OBJECTIVE
  The aim of this study was to describe the National Institutes of Health's experience initiating an islet isolation and transplantation center, including descriptions of our first six recipients, and lessons learned.
  
  
  METHODS
  Six 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.
  
  
  RESULTS
  All 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 17-22 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.
  
  
  CONCLUSIONS
  We 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.
authors.affiliation: Transplantation and Autoimmunity Branch, National Institutes of Health/Department of Health and Human Services, Bethesda, Maryland, USA.
authors.forename: Boaz
authors.initials: B
authors.lastname: Hirshberg
authors.forename: Kristina I
authors.initials: KI
authors.lastname: Rother
authors.forename: Benigno J
authors.initials: BJ
authors.lastname: Digon
authors.forename: Janet
authors.initials: J
authors.lastname: Lee
authors.forename: Jason L
authors.initials: JL
authors.lastname: Gaglia
authors.forename: Kenneth
authors.initials: K
authors.lastname: Hines
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Read
authors.forename: Richard
authors.initials: R
authors.lastname: Chang
authors.forename: Bradford J
authors.initials: BJ
authors.lastname: Wood
authors.forename: David M
authors.initials: DM
authors.lastname: Harlan
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001786:Blood Glucose / Q000378:metabolism; D000077561:Daclizumab; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000601:surgery*; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007003:Hypoglycemia / Q000453:epidemiology; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007165:Immunosuppression Therapy / Q000009:adverse effects / Q000379:methods; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016381:Islets of Langerhans Transplantation / Q000009:adverse effects; D008875:Middle Aged; D011183:Postoperative Complications / Q000145:classification / Q000453:epidemiology; D015203:Reproducibility of Results; D020123:Sirolimus / Q000627:therapeutic use*; D016559:Tacrolimus / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D001786:Blood Glucose; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D000077561:Daclizumab; D020123:Sirolimus; D016559:Tacrolimus