title: Expectations and strategies regarding islet transplantation: metabolic data from the GRAGIL 2 trial.
abstract: BACKGROUND
  Whether islet transplantation should be aimed at restoring insulin independence or providing adequate metabolic control is still debated. The GRAGIL2 trial was designed as a phase 1-2 study where primary outcome was the rate of insulin independence, and secondary outcome was the success rate defined by a composite score based upon basal C-peptide, HbA1c, hypoglycemic events, and exogenous insulin needs.
  
  
  METHODS
  C-peptide negative type 1 brittle diabetic patients experiencing severe hypoglycemia were eligible to receive a maximum of two islet preparations totalizing 10,000 IE/kg or more, with a threshold of 5,000 IE/kg for the first infusion, according to the Edmonton protocol, within the Swiss-French GRAGIL multicentric network. A sequential analysis with a triangular test was performed in every five patients after 6- and 12-month follow-up. Maximal inefficiency was set at 40% and minimal efficiency at 66%.
  
  
  RESULTS
  From September 2003 to October 2005, 10 patients were included. Median waiting time was 6.7 months (first injection) and 9 weeks (second injection). All but one patient received 11,089+/-505 IE/kg: one received a single graft of 5398 IE/kg. At 6 months, insulin independence and composite success rates were 6 of 10 and 6 of 10, respectively. At 12 months, insulin independence was observed in 3 of 10 patients and success in 5 of 10 patients.
  
  
  CONCLUSIONS
  Based upon our sequential analysis settings, islet transplantation failed to achieve the primary goal, insulin independence, but tended to succeed in reaching the secondary goal, successful metabolic control. Currently it appears to be a successful biological closed-loop glucose control method for brittle diabetes.
authors.affiliation: Department of Urology, University Hospital, Lyon, France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Badet
authors.forename: Pierre Y
authors.initials: PY
authors.lastname: Benhamou
authors.forename: Anne
authors.initials: A
authors.lastname: Wojtusciszyn
authors.forename: Reto
authors.initials: R
authors.lastname: Baertschiger
authors.forename: Laure
authors.initials: L
authors.lastname: Milliat-Guittard
authors.forename: Laurence
authors.initials: L
authors.lastname: Kessler
authors.forename: Alfred
authors.initials: A
authors.lastname: Penfornis
authors.forename: Charles
authors.initials: C
authors.lastname: Thivolet
authors.forename: Eric
authors.initials: E
authors.lastname: Renard
authors.forename: Dominico
authors.initials: D
authors.lastname: Bosco
authors.forename: Philippe
authors.initials: P
authors.lastname: Morel
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Morelon
authors.forename: François
authors.initials: F
authors.lastname: Bayle
authors.forename: Cyrille
authors.initials: C
authors.lastname: Colin
authors.forename: Thierry
authors.initials: T
authors.lastname: Berney
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D002986:Clinical Trials as Topic; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism* / Q000601:surgery*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007003:Hypoglycemia / Q000503:physiopathology*; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D016381:Islets of Langerhans Transplantation / Q000009:adverse effects / Q000379:methods*; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009901:Optic Nerve Diseases / Q000139:chemically induced; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D007166:Immunosuppressive Agents; D007328:Insulin