Prediction of the long-term metabolic success of the pancreatic graft function.
BACKGROUND
Strategies to prevent the return to the diabetic state for graft loss or failure or any other cause after pancreas transplantation require the identification of the subjects at risk. This study evaluated whether daily glucose, insulin, and c-peptide profiles and studies of insulin sensitivity and secretion after transplantation predict pancreatic graft failure.


METHODS
Fifty-three subjects with type 1 diabetes with end-stage renal failure who received a combined pancreas and kidney transplant underwent the following procedures 1 year after transplantation: 1-day metabolic profiles, sampling every 2 hours for plasma glucose, serum insulin, and c-peptide (n=51); an intravenous glucose tolerance test (IVGTT) to evaluate insulin secretion (n=48); and an euglycemic insulin clamp to evaluate insulin sensitivity (M value, n=14). The recipients were then followed up to 8 years (mean follow-up 4.8+/-0.3 years) to evaluate the return to the diabetic state.


RESULTS
Survival analysis showed that plasma glucose in the profiles and insulin secretion in IVGTT were strongly related to the risk of returning to the diabetic state. A cutoff value of mean daily plasma glucose >127 mg/dL, corresponding to the top quartile of the mean plasma glucose distribution in the profiles, predicted the return to the diabetic state within 4 years from transplantation with a 93% specificity and a 100% sensitivity. A cutoff value of insulin delta peak <32 microU/ml in the IVGTT predicted the return to the diabetic state within 4 years from transplantation with a 75% specificity and a 75% sensitivity. In contrast, the M value in the clamp was devoid of predictive value.


CONCLUSIONS
This study indicates that the mean 24-h plasma glucose 1 year after transplantation is the strongest predictor of the return to the diabetic state. The risk is related to defects in insulin secretion and not to insulin resistance. Metabolic profiles can be used to screen the subjects at risk to strictly monitor the graft function and to investigate early determinants of graft failure.
Battezzati
A
A
Amino Acid and Stable Isotopes Laboratory, San Raffaele Scientific Institute, Via Olgettina, 60, 20132 Milano, Italy. battezzati.alberto@hsr.it
Benedini
S
S
Caldara
R
R
Calori
G
G
Secchi
A
A
Pozza
G
G
Luzi
L
L
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D002940:Circadian Rhythm; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D010179:Pancreas / Q000378:metabolism*; D016035:Pancreas Transplantation; D011184:Postoperative Period; D011237:Predictive Value of Tests; D011379:Prognosis; D012008:Recurrence; D016019:Survival Analysis; D013997:Time Factors
D001786:Blood Glucose; D007328:Insulin