TY - JOUR
T1 - Islet transplantation for brittle type 1 diabetes
T2 - The UIC protocol
AU - Gangemi, A.
AU - Salehi, P.
AU - Hatipoglu, B.
AU - Martellotto, J.
AU - Barbaro, B.
AU - Kuechle, J. B.
AU - Qi, M.
AU - Wang, Y.
AU - Pallan, P.
AU - Owens, C.
AU - Bui, J.
AU - West, D.
AU - Kaplan, B.
AU - Benedetti, E.
AU - Oberholzer, J.
PY - 2008/6
Y1 - 2008/6
N2 - This prospective phase 1/2 trial investigated the safety and reproducibility of allogeneic islet transplantation (Tx) in type I diabetic (T1DM) patients and tested a strategy to achieve insulin-independence with lower islet mass. Ten C-peptide negative T1DM subjects with hypoglycemic unawareness received 1-3 intraportal allogeneic islet Tx and were followed for 15 months. Four subjects (Group 1) received the Edmonton immunosuppression regimen (daclizumab, sirolimus, tacrolimus). Six subjects (Group 2) received the University of Illinois protocol (etanercept, exenatide and the Edmonton regimen). All subjects became insulin- independent. Group 1 received a mean total number of islets (EIN) of 1460 080 ± 418 330 in 2 (n = 2) or 3 (n = 2) Tx, whereas Group 2 became insulin- independent after 1 Tx (537 495 ± 190 968 EIN, p = 0.028). All Group 1 subjects remained insulin free through the follow-up. Two Group 2 subjects resumed insulin: one after immunosuppression reduction during an infectious complication, the other with exenatide intolerance. HbA1c reached normal range in both groups (6.5 ± 0.6 at baseline to 5.6 ± 0.5 after 2-3 Tx in Group 1 vs. 7.8 ± 1.1 to 5.8 ± 0.3 after 1 Tx in Group 2). HYPO scores markedly decreased in both groups. Combined treatment of etanercept and exenatide improves islet graft function and facilitates achievement of insulin-independence with less islets.
AB - This prospective phase 1/2 trial investigated the safety and reproducibility of allogeneic islet transplantation (Tx) in type I diabetic (T1DM) patients and tested a strategy to achieve insulin-independence with lower islet mass. Ten C-peptide negative T1DM subjects with hypoglycemic unawareness received 1-3 intraportal allogeneic islet Tx and were followed for 15 months. Four subjects (Group 1) received the Edmonton immunosuppression regimen (daclizumab, sirolimus, tacrolimus). Six subjects (Group 2) received the University of Illinois protocol (etanercept, exenatide and the Edmonton regimen). All subjects became insulin- independent. Group 1 received a mean total number of islets (EIN) of 1460 080 ± 418 330 in 2 (n = 2) or 3 (n = 2) Tx, whereas Group 2 became insulin- independent after 1 Tx (537 495 ± 190 968 EIN, p = 0.028). All Group 1 subjects remained insulin free through the follow-up. Two Group 2 subjects resumed insulin: one after immunosuppression reduction during an infectious complication, the other with exenatide intolerance. HbA1c reached normal range in both groups (6.5 ± 0.6 at baseline to 5.6 ± 0.5 after 2-3 Tx in Group 1 vs. 7.8 ± 1.1 to 5.8 ± 0.3 after 1 Tx in Group 2). HYPO scores markedly decreased in both groups. Combined treatment of etanercept and exenatide improves islet graft function and facilitates achievement of insulin-independence with less islets.
KW - Islet transplantation
KW - Transplantation cell therapy
KW - Transplantation research
KW - Type I diabetes
UR - http://www.scopus.com/inward/record.url?scp=44449092051&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=44449092051&partnerID=8YFLogxK
U2 - 10.1111/j.1600-6143.2008.02234.x
DO - 10.1111/j.1600-6143.2008.02234.x
M3 - Article
C2 - 18444920
AN - SCOPUS:44449092051
SN - 1600-6135
VL - 8
SP - 1250
EP - 1261
JO - American Journal of Transplantation
JF - American Journal of Transplantation
IS - 6
ER -