Supplemental islet infusions restore insulin independence after graft dysfunction in islet transplant recipients.
BACKGROUND
The ability of supplemental islet infusions (SII) to restore insulin independence in islet transplant recipients with graft dysfunction has been attributed to the coadministration of exenatide. However, improving islet transplant outcomes could explain the success of SII. We aimed to determine the effect on islet graft function and insulin independence of SII using these new protocols, without the use of exenatide.


METHODS
Seventeen islet transplant recipients underwent SIIs after developing graft dysfunction requiring insulin use. For induction therapy, four subjects received daclizumab induction therapy, whereas 13 subjects received thymoglobulin and etanercept. Maintenance immunosuppression consisted of sirolimus+tacrolimus or tacrolimus+cellcept.


RESULTS
SII was performed 49.3+/-4.8 months (mean+/-SEM) after the preceding islet transplant. Subjects received significantly lower islet mass with their SII compared with initial transplant(s) (6076+/-492 vs. 9071+/-796 IEQ/kg; P=0.003). Fifteen of the 17 subjects (88.2%) became insulin independent 2.4+/-0.5 months after SII. Insulin-independent duration after SII exceeded that of the initial transplant(s) (24.8+/-2.2 vs. 14.2+/-2.6 months by Kaplan-Meier analysis, P=0.009). Subjects show improved glycemic control after SII (HbA1c 7.0%+/-0.2% pre-SII vs. 6.1%+/-0.2% post-SII, P=0.005) and did not become immunosensitized.


CONCLUSIONS
Using current protocols, SII in the absence of exenatide results in impressive insulin-independence rates and the durability of insulin independence seems to be promising. However, a beneficial effect of exenatide should not be discounted until tested in randomized controlled studies.
Koh
Angela
A
Clinical Islet Transplant Program, University of Alberta, Edmonton, AB, Canada.
Imes
Sharleen
S
Kin
Tatsuya
T
Dinyari
Parastoo
P
Malcolm
Andrew
A
Toso
Christian
C
Shapiro
A M James
AM
Senior
Peter
P
D000961:Antilymphocyte Serum / Q000627:therapeutic use; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D004359:Drug Therapy, Combination; D000068800:Etanercept; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy / Q000453:epidemiology; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007074:Immunoglobulin G / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use*; D016381:Islets of Langerhans Transplantation / Q000276:immunology / Q000379:methods*; D008297:Male; D011183:Postoperative Complications / Q000097:blood / Q000188:drug therapy; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D020123:Sirolimus / Q000627:therapeutic use; D016559:Tacrolimus / Q000627:therapeutic use
D000961:Antilymphocyte Serum; D001786:Blood Glucose; D002096:C-Peptide; D000068800:Etanercept; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D007328:Insulin; D018124:Receptors, Tumor Necrosis Factor; D020123:Sirolimus; D016559:Tacrolimus