title: Primary graft function, metabolic control, and graft survival after islet transplantation.
abstract: OBJECTIVE To investigate the influence of primary graft function (PGF) on graft survival and metabolic control after islet transplantation with the Edmonton protocol. RESEARCH DESIGN AND METHODS A total of 14 consecutive patients with brittle type 1 diabetes were enrolled in this phase 2 study and received median 12,479 islet equivalents per kilogram of body weight (interquartile range 11,072-15,755) in two or three sequential infusions within 67 days (44-95). PGF was estimated 1 month after the last infusion by the beta-score, a previously validated index (range 0-8) based on insulin or oral treatment requirements, plasma C-peptide, blood glucose, and A1C. Primary outcome was graft survival, defined as insulin independence with A1C < or =6.5%. RESULTS All patients gained insulin independence within 12 days (6-23) after the last infusion. PGF was optimal (beta-score > or =7) in nine patients and suboptimal (beta-score < or =6) in five. At last follow-up, 3.3 years (2.8-4.0) after islet transplantation, eight patients (57%) remained insulin independent with A1C < or =6.5%, including seven patients with optimal PGF (78%) and one with suboptimal PGF (20%) (P = 0.01, log-rank test). Graft survival was not significantly influenced by HLA mismatches or by preexisting islet autoantibodies. A1C, mean glucose, glucose variability (assessed with continuous glucose monitoring system), and glucose tolerance (using an oral glucose tolerance test) were markedly improved when compared with baseline values and were significantly lower in patients with optimal PGF than in those with suboptimal PGF. CONCLUSIONS Optimal PGF was associated with prolonged graft survival and better metabolic control after islet transplantation. This early outcome may represent a valuable end point in future clinical trials.
authors.affiliation: University Lille Nord de France, Lille, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Vantyghem
authors.forename: Julie
authors.initials: J
authors.lastname: Kerr-Conte
authors.forename: Laurent
authors.initials: L
authors.lastname: Arnalsteen
authors.forename: Geraldine
authors.initials: G
authors.lastname: Sergent
authors.forename: Frederique
authors.initials: F
authors.lastname: Defrance
authors.forename: Valery
authors.initials: V
authors.lastname: Gmyr
authors.forename: Nicole
authors.initials: N
authors.lastname: Declerck
authors.forename: Violeta
authors.initials: V
authors.lastname: Raverdy
authors.forename: Brigitte
authors.initials: B
authors.lastname: Vandewalle
authors.forename: Pascal
authors.initials: P
authors.lastname: Pigny
authors.forename: Christian
authors.initials: C
authors.lastname: Noel
authors.forename: Francois
authors.initials: F
authors.lastname: Pattou
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery*; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007328:Insulin; D050417:Insulin-Secreting Cells / Q000637:transplantation; D016381:Islets of Langerhans Transplantation / Q000009:adverse effects / Q000379:methods / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011169:Portal Vein / Q000601:surgery; D016559:Tacrolimus / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007166:Immunosuppressive Agents; D007328:Insulin; D016559:Tacrolimus