title: Acute insulin response to arginine in deceased donors predicts the outcome of human islet isolation.
abstract: Despite a stringent donor selection, human islet isolation remains frustratingly unpredictable. In this study, we measured acute insulin response to arginine (AIRarg), an in vivo surrogate measure of islet mass, in 29 human deceased donors before organ donation, and correlated values with the outcome of islet isolation. Thirteen isolations (45%) met the threshold for clinical islet transplantation. Among all measured donor characteristics, the only discriminating variable between successful or unsuccessful isolations was donor AIRarg (p < 0.01). Using a threshold of 55 microIU/mL (ROC curve AUC: 72%), isolation was successful in 12/19 donors with high AIRarg and in 1/10 donors with low AIRarg (p < 0.001). The negative and positive predictive values were 90 and 63%, respectively. If used to select donors in the entire cohort, AIRarg would have increased our success rate by 40% and avoided 56% of unsuccessful isolations while missing only 8% of successful preparations. Our results suggest that donor AIRarg is markedly superior to body mass index (BMI) and other criteria currently used to predict isolation outcome. If routinely performed in deceased donors, this simple test could significantly reduce the failure rate of human islet isolation.
authors.affiliation: INSERM U859, Thérapie Cellulaire du Diabète, Faculté de Médecine, Lille, France.
authors.forename: T
authors.initials: T
authors.lastname: Hubert
authors.forename: G
authors.initials: G
authors.lastname: Strecker
authors.forename: V
authors.initials: V
authors.lastname: Gmyr
authors.forename: L
authors.initials: L
authors.lastname: Arnalsteen
authors.forename: D
authors.initials: D
authors.lastname: Garrigue
authors.forename: R
authors.initials: R
authors.lastname: Ezzouaoui
authors.forename: R
authors.initials: R
authors.lastname: Caiazzo
authors.forename: G
authors.initials: G
authors.lastname: Dezfoulian
authors.forename: B
authors.initials: B
authors.lastname: Averland
authors.forename: B
authors.initials: B
authors.lastname: Vandewalle
authors.forename: M C
authors.initials: MC
authors.lastname: Vantyghem
authors.forename: J
authors.initials: J
authors.lastname: Kerr-Conte
authors.forename: F
authors.initials: F
authors.lastname: Pattou
mesh_terms: D001120:Arginine / Q000494:pharmacology*; D001926:Brain Death; D002102:Cadaver; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D016381:Islets of Langerhans Transplantation / Q000502:physiology*; D011237:Predictive Value of Tests; D014019:Tissue Donors; D020858:Tissue and Organ Harvesting / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D007328:Insulin; D001120:Arginine