Succesful transplantation of human islets in recipients bearing a kidney graft

被引:38
作者
Bertuzzi, F
Grohovaz, F
Maffi, P
Caumo, A
Aldrighetti, L
Nano, R
Hengster, P
Calori, G
Di Carlo, V
Bonifacio, E
Secchi, A
机构
[1] Ist Sci San Raffaele, Dept Surg, I-20132 Milan, Italy
[2] Ist Sci San Raffaele, CNR, Cellular & Mol Pharmacol Ctr, I-20132 Milan, Italy
[3] Ist Sci San Raffaele, B Ceccarelli Ctr, Dept Neurosci, I-20132 Milan, Italy
[4] Ist Sci San Raffaele, Dept Med, I-20132 Milan, Italy
[5] Ist Sci San Raffaele, Stat Unit, I-20132 Milan, Italy
[6] Univ Innsbruck Hosp, Dept Transplant Surg, A-6020 Innsbruck, Austria
关键词
islet transplantation; kidney transplantation; primary non-function; insulin release; proinsulin release; intravenous glucose tolerance test; arginine test; insulin resistance;
D O I
10.1007/s125-002-8247-2
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Aims/hypothesis. Islet transplantation is a minimally invasive approach to curing Type I (insulin-dependent) diabetes mellitus. Success has recently been reported in patients receiving solitary islet transplants but the outcome in patients receiving islets together with, or after, kidney transplants has been limited and unpredictable. Methods. Here we report successful islet transplantation in a cohort of 15 patients with Type I diabetes who were followed for at least 1 year after islet transplantation, after having already received kidney allografts because of end-stage nephropathy. Results. C-peptide after transplantation was higher than 0.17 nmol/l in all 15 recipients, reflecting the absence of primary non-function. Insulin requirement was reduced by over 50 % in all but one patient, and insulin independence was achieved in 10 (66%) recipients, five of whom now have stable, prolonged insulin independence, well controlled fasting glycaemia, a substantial first-phase and normal second-phase response to glucose, normal insulin sensitivity (HOMA analyses) and HbA(1e) of under 6.2% (33, 26, 18, 13 and 12 months after transplantation respectively). Of importance for patient management, an assessment of fasting blood glucose and proinsulin values following overnight withdrawal of insulin administration one month after transplantation was a potent predictor of insulin independence, and could be used to decide patients who should have further islet preparations. Conclusion/interpretation. These findings support the use of islet transplantation as a cure for Type I diabetes in patients with severe complications.
引用
收藏
页码:77 / 84
页数:8
相关论文
共 29 条
[1]   Long-term function (6 years) of islet allografts in type 1 diabetes [J].
Alejandro, R ;
Lehmann, R ;
Ricordi, C ;
Kenyon, NS ;
Angelico, MC ;
Burke, G ;
Esquenazi, V ;
Nery, J ;
Betancourt, AE ;
Kong, SS ;
Miller, J ;
Mintz, DH .
DIABETES, 1997, 46 (12) :1983-1989
[2]   Prediction of the long-term metabolic success of the pancreatic graft function [J].
Battezzati, A ;
Benedini, S ;
Caldara, R ;
Calori, G ;
Secchi, A ;
Pozza, G ;
Luzi, L .
TRANSPLANTATION, 2001, 71 (11) :1560-1565
[3]   Islet transplantation [J].
Berney, T ;
Ricordi, C .
CELL TRANSPLANTATION, 1999, 8 (05) :461-464
[4]   Mechanisms of coordination of Ca2+ signals in pancreatic islet cells [J].
Bertuzzi, F ;
Davalli, AM ;
Nano, R ;
Socci, C ;
Codazzi, F ;
Fesce, R ;
Di Carlo, V ;
Pozza, G ;
Grohovaz, F .
DIABETES, 1999, 48 (10) :1971-1978
[5]  
BRENDEL MD, 1999, NEWSLETTER, V8
[6]   Improved survival of intraportal pancreatic islet cell allografts in patients with type-1 diabetes mellitus by refined peritransplant management [J].
Bretzel, RG ;
Brandhorst, D ;
Brandhorst, H ;
Eckhard, M ;
Ernst, W ;
Freimann, S ;
Rau, W ;
Weimar, B ;
Rauber, K ;
Hering, BJ ;
Brendel, MD .
JOURNAL OF MOLECULAR MEDICINE-JMM, 1999, 77 (01) :140-143
[7]   INSULIN-SECRETION, INSULIN ACTION AND NON-INSULIN-DEPENDENT GLUCOSE-UPTAKE IN PANCREAS TRANSPLANT RECIPIENTS [J].
CHRISTIANSEN, E ;
TIBELL, A ;
VOLUND, A ;
RASMUSSEN, K ;
TYDEN, G ;
PEDERSEN, O ;
CHRISTENSEN, NJ ;
MADSBAD, S .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1994, 79 (06) :1561-1569
[8]   Insights from a successful case of intrahepatic islet transplantation into a type 1 diabetic patient [J].
Davalli, AM ;
Maffi, P ;
Socci, C ;
Sanvito, F ;
Freschi, M ;
Bertuzzi, F ;
Falqui, L ;
Di Carlo, V ;
Pozza, G ;
Secchi, A .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2000, 85 (10) :3847-3852
[9]   ABNORMAL SENSITIVITY TO GLUCOSE OF HUMAN ISLETS CULTURED IN A HIGH GLUCOSE MEDIUM - PARTIAL REVERSIBILITY AFTER AN ADDITIONAL CULTURE IN A NORMAL GLUCOSE MEDIUM [J].
DAVALLI, AM ;
RICORDI, C ;
SOCCI, C ;
BRAGHI, S ;
BERTUZZI, F ;
FATTOR, B ;
DICARLO, V ;
PONTIROLI, AE ;
POZZA, G .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1991, 72 (01) :202-208
[10]   CELLULAR HYPERCALCEMIA IS AN EARLY EVENT IN DEOXYCHOLATE INJURY OF RABBIT GASTRIC-MUCOSAL CELLS [J].
DZIKI, AJ ;
BATZRI, S ;
HARMON, JW ;
MOLLOY, M .
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 1995, 269 (02) :G287-G296