Diabetes
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ryan, E. A.
Right arrow Articles by Shapiro, A.M. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ryan, E. A.
Right arrow Articles by Shapiro, A.M. J.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Diabetes 54:2060-2069, 2005
© 2005 by the American Diabetes Association, Inc.

Five-Year Follow-Up After Clinical Islet Transplantation

Edmond A. Ryan1, Breay W. Paty1, Peter A. Senior1, David Bigam2, Eman Alfadhli1, Norman M. Kneteman2, Jonathan R.T. Lakey2, and A.M. James Shapiro2

1 Department of Medicine, Clinical Islet Transplant Program, University of Alberta and Capital Health, Edmonton, Alberta, Canada
2 Department of Surgery, Clinical Islet Transplant Program, University of Alberta and Capital Health, Edmonton, Alberta, Canada

Islet transplantation can restore endogenous ß-cell function to subjects with type 1 diabetes. Sixty-five patients received an islet transplant in Edmonton as of 1 November 2004. Their mean age was 42.9 ± 1.2 years, their mean duration of diabetes was 27.1 ± 1.3 years, and 57% were women. The main indication was problematic hypoglycemia. Forty-four patients completed the islet transplant as defined by insulin independence, and three further patients received >16,000 islet equivalents (IE)/kg but remained on insulin and are deemed complete. Those who became insulin independent received a total of 799,912 ± 30,220 IE (11,910 ± 469 IE/kg). Five subjects became insulin independent after one transplant. Fifty-two patients had two transplants, and 11 subjects had three transplants. In the completed patients, 5-year follow-up reveals that the majority (~80%) have C-peptide present post–islet transplant, but only a minority (~10%) maintain insulin independence. The median duration of insulin independence was 15 months (interquartile range 6.2–25.5). The HbA1c (A1C) level was well controlled in those off insulin (6.4% [6.1–6.7]) and in those back on insulin but C-peptide positive (6.7% [5.9–7.5]) and higher in those who lost all graft function (9.0% [6.7–9.3]) (P < 0.05). Those who resumed insulin therapy did not appear more insulin resistant compared with those off insulin and required half their pretransplant daily dose of insulin but had a lower increment of C-peptide to a standard meal challenge (0.44 ± 0.06 vs. 0.76 ± 0.06 nmol/l, P < 0.001). The Hypoglycemic score and lability index both improved significantly posttransplant. In the 128 procedures performed, bleeding occurred in 15 and branch portal vein thrombosis in 5 subjects. Complications of immunosuppressive therapy included mouth ulcers, diarrhea, anemia, and ovarian cysts. Of the 47 completed patients, 4 required retinal laser photocoagulation or vitrectomy and 5 patients with microalbuminuria developed macroproteinuria. The need for multiple antihypertensive medications increased from 6% pretransplant to 42% posttransplant, while the use of statin therapy increased from 23 to 83% posttransplant. There was no change in the neurothesiometer scores pre- versus posttransplant. In conclusion, islet transplantation can relieve glucose instability and problems with hypoglycemia. C-peptide secretion was maintained in the majority of subjects for up to 5 years, although most reverted to using some insulin. The results, though promising, still point to the need for further progress in the availability of transplantable islets, improving islet engraftment, preserving islet function, and reducing toxic immunosuppression.

Address correspondence and reprint requests to Edmond A. Ryan, Clinical Islet Transplant Program, 2000 College Plaza, 8215 112th St., Edmonton, Alberta, Canada T6G 2C8. E-mail: edmond.ryan{at}ualberta.ca

Abbreviations: CBC, complete blood count; CMV, cytomegalovirus; HOMA, homeostasis model assessment; HYPO score, Hypoglycemic score; LI, lability index; LFT, liver function test; PRA, panel reactive antibody


Add to CiteULike CiteULike   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 DiabetesHome page
B. Movahedi, C. Gysemans, D. Jacobs-Tulleneers-Thevissen, C. Mathieu, and D. Pipeleers
Pancreatic Duct Cells in Human Islet Cell Preparations Are a Source of Angiogenic Cytokines Interleukin-8 and Vascular Endothelial Growth Factor
Diabetes, August 1, 2008; 57(8): 2128 - 2136.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
J. Olerud, M. Johansson, J. Lawler, N. Welsh, and P.-O. Carlsson
Improved Vascular Engraftment and Graft Function After Inhibition of the Angiostatic Factor Thrombospondin-1 in Mouse Pancreatic Islets
Diabetes, July 1, 2008; 57(7): 1870 - 1877.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
J. J. Meier, A. E. Butler, Y. Saisho, T. Monchamp, R. Galasso, A. Bhushan, R. A. Rizza, and P. C. Butler
{beta}-Cell Replication Is the Primary Mechanism Subserving the Postnatal Expansion of {beta}-Cell Mass in Humans
Diabetes, June 1, 2008; 57(6): 1584 - 1594.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
J. A. Emamaullee, J. Davis, R. Pawlick, C. Toso, S. Merani, S.-X. Cai, B. Tseng, and A.M. J. Shapiro
The Caspase Selective Inhibitor EP1013 Augments Human Islet Graft Function and Longevity in Marginal Mass Islet Transplantation in Mice
Diabetes, June 1, 2008; 57(6): 1556 - 1566.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
S.-J. Kim, C. Nian, D. J. Doudet, and C. H.S. McIntosh
Inhibition of Dipeptidyl Peptidase IV With Sitagliptin (MK0431) Prolongs Islet Graft Survival in Streptozotocin-Induced Diabetic Mice
Diabetes, May 1, 2008; 57(5): 1331 - 1339.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
S. A. Hinke
Finding GAD: Early Detection of {beta}-Cell Injury
Endocrinology, October 1, 2007; 148(10): 4568 - 4571.
[Full Text] [PDF]

Home page
 DiabetesHome page
Y. Lee, M. Ravazzola, B.-H. Park, Y. K. Bashmakov, L. Orci, and R. H. Unger
Metabolic Mechanisms of Failure of Intraportally Transplanted Pancreatic {beta}-Cells in Rats: Role of Lipotoxicity and Prevention by Leptin
Diabetes, September 1, 2007; 56(9): 2295 - 2301.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
D. Su, N. Zhang, J. He, S. Qu, S. Slusher, R. Bottino, S. Bertera, J. Bromberg, and H. H. Dong
Angiopoietin-1 Production in Islets Improves Islet Engraftment and Protects Islets From Cytokine-Induced Apoptosis
Diabetes, September 1, 2007; 56(9): 2274 - 2283.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
M. R. Rickels, M. Kamoun, J. Kearns, J. F. Markmann, and A. Naji
Evidence for Allograft Rejection in an Islet Transplant Recipient and Effect on {beta}-Cell Secretory Capacity
J. Clin. Endocrinol. Metab., July 1, 2007; 92(7): 2410 - 2414.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
J. Lau, G. Mattsson, C. Carlsson, D. Nyqvist, M. Kohler, P.-O. Berggren, L. Jansson, and P.-O. Carlsson
Implantation Site-Dependent Dysfunction of Transplanted Pancreatic Islets
Diabetes, June 1, 2007; 56(6): 1544 - 1550.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
J. A. Emamaullee, L. Stanton, C. Schur, and A.M. J. Shapiro
Caspase Inhibitor Therapy Enhances Marginal Mass Islet Graft Survival and Preserves Long-Term Function in Islet Transplantation
Diabetes, May 1, 2007; 56(5): 1289 - 1298.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
P. Fiorina, M. Jurewicz, K. Tanaka, N. Behazin, A. Augello, A. Vergani, U. Von Adrian, N. R. Smith, M. H. Sayegh, and R. Abdi
Characterization of Donor Dendritic Cells and Enhancement of Dendritic Cell Efflux With cc-Chemokine Ligand 21: A Novel Strategy to Prolong Islet Allograft Survival
Diabetes, April 1, 2007; 56(4): 912 - 920.
[Abstract] [Full Text] [PDF]

Home page
 Postgrad. Med. J.Home page
P Srinivasan, G C Huang, S A Amiel, and N D Heaton
Islet cell transplantation
Postgrad. Med. J., April 1, 2007; 83(978): 224 - 229.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
M. R. Rickels, M. H. Schutta, R. Mueller, S. Kapoor, J. F. Markmann, A. Naji, and K. L. Teff
Glycemic Thresholds for Activation of Counterregulatory Hormone and Symptom Responses in Islet Transplant Recipients
J. Clin. Endocrinol. Metab., March 1, 2007; 92(3): 873 - 879.
[Abstract] [Full Text] [PDF]

Home page
 Diabetes CareHome page
F. Bertuzzi and C. Ricordi
Prediction of Clinical Outcome in Islet Allotransplantation
Diabetes Care, February 1, 2007; 30(2): 410 - 417.
[Full Text] [PDF]

Home page
 J EndocrinolHome page
M. Montolio, M. Biarnes, N. Tellez, J. Escoriza, J. Soler, and E. Montanya
Interleukin-1{beta} and inducible form of nitric oxide synthase expression in early syngeneic islet transplantation
J. Endocrinol., January 1, 2007; 192(1): 169 - 177.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
R. A. Ritzel, J. J. Meier, C.-Y. Lin, J. D. Veldhuis, and P. C. Butler
Human Islet Amyloid Polypeptide Oligomers Disrupt Cell Coupling, Induce Apoptosis, and Impair Insulin Secretion in Isolated Human Islets
Diabetes, January 1, 2007; 56(1): 65 - 71.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
N. A. Sherry, J. A. Kushner, M. Glandt, T. Kitamura, A.-M. B. Brillantes, and K. C. Herold
Effects of Autoimmunity and Immune Therapy on {beta}-Cell Turnover in Type 1 Diabetes
Diabetes, December 1, 2006; 55(12): 3238 - 3245.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
B. Keymeulen, P. Gillard, C. Mathieu, B. Movahedi, G. Maleux, G. Delvaux, D. Ysebaert, B. Roep, E. Vandemeulebroucke, M. Marichal, et al.
Correlation between beta cell mass and glycemic control in type 1 diabetic recipients of islet cell graft
PNAS, November 14, 2006; 103(46): 17444 - 17449.
[Abstract] [Full Text] [PDF]

Home page
 NEJMHome page
A.M. J. Shapiro, C. Ricordi, B. J. Hering, H. Auchincloss, R. Lindblad, R. P. Robertson, A. Secchi, M. D. Brendel, T. Berney, D. C. Brennan, et al.
International Trial of the Edmonton Protocol for Islet Transplantation.
N. Engl. J. Med., September 28, 2006; 355(13): 1318 - 1330.
[Abstract] [Full Text] [PDF]

Home page
 NEJMHome page
J. S. Bromberg and D. LeRoith
Diabetes cure--is the glass half full?
N. Engl. J. Med., September 28, 2006; 355(13): 1372 - 1374.
[Full Text] [PDF]

Home page
 DiabetesHome page
N. V. Evgenov, Z. Medarova, J. Pratt, P. Pantazopoulos, S. Leyting, S. Bonner-Weir, and A. Moore
In Vivo Imaging of Immune Rejection in Transplanted Pancreatic Islets
Diabetes, September 1, 2006; 55(9): 2419 - 2428.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
N. Zhang, D. Su, S. Qu, T. Tse, R. Bottino, A.N. Balamurugan, J. Xu, J. S. Bromberg, and H. H. Dong
Sirolimus Is Associated With Reduced Islet Engraftment and Impaired {beta}-Cell Function
Diabetes, September 1, 2006; 55(9): 2429 - 2436.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
J. J. Meier, I. Hong-McAtee, R. Galasso, J. D. Veldhuis, A. Moran, B. J. Hering, and P. C. Butler
Intrahepatic transplanted islets in humans secrete insulin in a coordinate pulsatile manner directly into the liver.
Diabetes, August 1, 2006; 55(8): 2324 - 2332.
[Abstract] [Full Text] [PDF]

Home page
 CMAJHome page
K. M. Gillespie
Type 1 diabetes: pathogenesis and prevention.
Can. Med. Assoc. J., July 18, 2006; 175(2): 165 - 170.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
J. A. Emamaullee and A.M. J. Shapiro
Interventional Strategies to Prevent {beta}-Cell Apoptosis in Islet Transplantation.
Diabetes, July 1, 2006; 55(7): 1907 - 1914.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
M. R. Rickels, A. Naji, and K. L. Teff
Insulin Sensitivity, Glucose Effectiveness, and Free Fatty Acid Dynamics after Human Islet Transplantation for Type 1 Diabetes
J. Clin. Endocrinol. Metab., June 1, 2006; 91(6): 2138 - 2144.
[Abstract] [Full Text] [PDF]

Home page
 NEJMHome page
D. Stainier
No Stem Cell Is an Islet (Yet)
N. Engl. J. Med., February 2, 2006; 354(5): 521 - 523.
[Full Text] [PDF]

Home page
 DiabetesHome page
A. Toyofuku, Y. Yasunami, K. Nabeyama, M. Nakano, M. Satoh, N. Matsuoka, J. Ono, T. Nakayama, M. Taniguchi, M. Tanaka, et al.
Natural Killer T-Cells Participate in Rejection of Islet Allografts in the Liver of Mice
Diabetes, January 1, 2006; 55(1): 34 - 39.
[Abstract] [Full Text] [PDF]

Home page
 Diabetes CareHome page
R. Calafiore, G. Basta, G. Luca, A. Lemmi, M. P. Montanucci, G. Calabrese, L. Racanicchi, F. Mancuso, and P. Brunetti
Microencapsulated Pancreatic Islet Allografts Into Nonimmunosuppressed Patients With Type 1 Diabetes: First two cases
Diabetes Care, January 1, 2006; 29(1): 137 - 138.
[Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
T. B. Strom
Saving islets from allograft rejection
PNAS, September 6, 2005; 102(36): 12651 - 12652.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 2005 by the American Diabetes Association.