Early metabolic markers of islet allograft dysfunction.
BACKGROUND
Islet transplantation can restore normoglycemia to patients with unstable type 1 diabetes mellitus, but long-term insulin independence is usually not sustained. Identification of predictor(s) of islet allograft dysfunction (IGD) might allow for early intervention(s) to preserve functional islet mass.


METHODS
Fourteen islet transplantation recipients with long-term history of type 1 diabetes mellitus underwent metabolic testing by mixed meal tolerance test, intravenous glucose tolerance test, and arginine stimulation test every 3 months postislet transplant completion. Metabolic responses were compared between subjects who maintained insulin independence at 18 months (group 1; n=5) and those who restarted insulin within 18 months (group 2; n=9). Data were analyzed before development of islet graft dysfunction and while insulin independent.


RESULTS
The 90-min glucose, time-to-peak C-peptide, and area under the curve for glucose were consistently higher in group 2 and increased as a function of time. At 12 months, acute insulin release to glucose in group 2 was markedly reduced as compared with baseline (5.62+/-1.21 microIU/mL, n=4 vs. 16.14+/-3.69 microIU/mL, n=8), whereas it remained stable in group 1 (22.36+/-4.98 microIU/mL, n=5 vs. 27.70+/-2.83 microIU/mL, n=5). Acute insulin release to glucose, acute C-peptide release to glucose (ACpRg), and mixed meal stimulation index were significantly decreased and time-to-peak C-peptide, 90-min glucose, and area under the curve for glucose were significantly increased when measured at time points preceding intervals where IGD occurred compared with intervals where there was no IGD.


CONCLUSIONS
The intravenous glucose tolerance test and mixed meal tolerance test may be useful in the prediction of IGD and should be essential components of the metabolic testing of islet transplant recipients.
Baidal
David A
DA
Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
Faradji
Raquel N
RN
Messinger
Shari
S
Froud
Tatiana
T
Monroy
Kathy
K
Ricordi
Camillo
C
Alejandro
Rodolfo
R
D001120:Arginine; D001364:Awareness; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery; D004334:Drug Administration Schedule; D005215:Fasting; D005500:Follow-Up Studies; D005951:Glucose Tolerance Test; D006801:Humans; D007003:Hypoglycemia / Q000503:physiopathology; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D016381:Islets of Langerhans Transplantation / Q000009:adverse effects* / Q000502:physiology; D011183:Postoperative Complications / Q000175:diagnosis*; D014184:Transplantation, Homologous
D001786:Blood Glucose; D002096:C-Peptide; D007004:Hypoglycemic Agents; D007328:Insulin; D001120:Arginine