Islet transplantation for brittle type 1 diabetes: The UIC protocol

A. Gangemi, P. Salehi, B. Hatipoglu, J. Martellotto, B. Barbaro, J. B. Kuechle, M. Qi, Y. Wang, P. Pallan, C. Owens, J. Bui, D. West, B. Kaplan, E. Benedetti, J. Oberholzer

Research output: Contribution to journalArticle

120 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1250-1261
Number of pages12
JournalAmerican Journal of Transplantation
Volume8
Issue number6
DOIs
StatePublished - Jun 2008
Externally publishedYes

Fingerprint

Islets of Langerhans Transplantation
Type 1 Diabetes Mellitus
Insulin
Immunosuppression
C-Peptide
Homologous Transplantation
Tacrolimus
Sirolimus
Hypoglycemic Agents
Reference Values
Transplants
Safety
exenatide

Keywords

  • Islet transplantation
  • Transplantation cell therapy
  • Transplantation research
  • Type I diabetes

ASJC Scopus subject areas

  • Immunology

Cite this

Gangemi, A., Salehi, P., Hatipoglu, B., Martellotto, J., Barbaro, B., Kuechle, J. B., ... Oberholzer, J. (2008). Islet transplantation for brittle type 1 diabetes: The UIC protocol. American Journal of Transplantation, 8(6), 1250-1261. https://doi.org/10.1111/j.1600-6143.2008.02234.x

Islet transplantation for brittle type 1 diabetes : The UIC protocol. / Gangemi, A.; Salehi, P.; Hatipoglu, B.; Martellotto, J.; Barbaro, B.; Kuechle, J. B.; Qi, M.; Wang, Y.; Pallan, P.; Owens, C.; Bui, J.; West, D.; Kaplan, B.; Benedetti, E.; Oberholzer, J.

In: American Journal of Transplantation, Vol. 8, No. 6, 06.2008, p. 1250-1261.

Research output: Contribution to journalArticle

Gangemi, A, Salehi, P, Hatipoglu, B, Martellotto, J, Barbaro, B, Kuechle, JB, Qi, M, Wang, Y, Pallan, P, Owens, C, Bui, J, West, D, Kaplan, B, Benedetti, E & Oberholzer, J 2008, 'Islet transplantation for brittle type 1 diabetes: The UIC protocol', American Journal of Transplantation, vol. 8, no. 6, pp. 1250-1261. https://doi.org/10.1111/j.1600-6143.2008.02234.x
Gangemi A, Salehi P, Hatipoglu B, Martellotto J, Barbaro B, Kuechle JB et al. Islet transplantation for brittle type 1 diabetes: The UIC protocol. American Journal of Transplantation. 2008 Jun;8(6):1250-1261. https://doi.org/10.1111/j.1600-6143.2008.02234.x
Gangemi, A. ; Salehi, P. ; Hatipoglu, B. ; Martellotto, J. ; Barbaro, B. ; Kuechle, J. B. ; Qi, M. ; Wang, Y. ; Pallan, P. ; Owens, C. ; Bui, J. ; West, D. ; Kaplan, B. ; Benedetti, E. ; Oberholzer, J. / Islet transplantation for brittle type 1 diabetes : The UIC protocol. In: American Journal of Transplantation. 2008 ; Vol. 8, No. 6. pp. 1250-1261.
@article{9c36f4181c1d4d6abb2beac9e01a4837,
title = "Islet transplantation for brittle type 1 diabetes: The UIC protocol",
abstract = "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.",
keywords = "Islet transplantation, Transplantation cell therapy, Transplantation research, Type I diabetes",
author = "A. Gangemi and P. Salehi and B. Hatipoglu and J. Martellotto and B. Barbaro and Kuechle, {J. B.} and M. Qi and Y. Wang and P. Pallan and C. Owens and J. Bui and D. West and B. Kaplan and E. Benedetti and J. Oberholzer",
year = "2008",
month = "6",
doi = "10.1111/j.1600-6143.2008.02234.x",
language = "English (US)",
volume = "8",
pages = "1250--1261",
journal = "American Journal of Transplantation",
issn = "1600-6135",
publisher = "Wiley-Blackwell",
number = "6",

}

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

VL - 8

SP - 1250

EP - 1261

JO - American Journal of Transplantation

JF - American Journal of Transplantation

SN - 1600-6135

IS - 6

ER -