LONG-TERM FUNCTION (6 YEARS) OF ISLET ALLOGRAFTS IN TYPE-1 DIABETES

Eight type 1 diabetic patients, ages 29-41 years, with mean diabetes d uration of 23 years (range 18-29 years) received islet transplants fro m 1 to 5 donors. Seven patients had stable kidney allografts 1-11 year s before the islet transplant, and one patient had a simultaneous isle t-kidney allograft. Patients' blood glucose control was poor as reflec ted by the mean +/-SD HbA(1c) of 9.1 +/- 1.7% before transplant. Of th e first three patients, two (1 and 3) achieved insulin independence fo r 36 and 38 days, respectively. Two recipients rejected their islet gr afts within 1 month (2 and 8) and therefore were excluded from analysi s. The HbA(1c) and insulin requirement of the six remaining patients w ho had persistent islet function for more than 60 days was significant ly reduced from 9.3 +/- 1.9 to 6.4 +/- 1.0% (P = 0.002) and from 0.75 +/- 0.15 to 0.35 +/- 0.12 U.kg(-1).day(-1) (P < 0.001), respectively. The two patients-with the longest graft survival (4 and 6) achieved a normalization or near-normalization of their HbA(1c) levels during 6 y ears in the absence of severe episodes of hypoglycemia. As demonstrate d by a decline in C-peptide response during Sustacal challenge tests o ver a 6-year period, there was a diminution of islet allograft functio n over time, despite persistence of normal or near normal HbA(1c). We concluded that transplantation of allogeneic islets with an islet mass comparable with whole or segmental pancreas transplants in type 1 dia betic patients can result in long-term islet allograft function; furth er, we concluded that, in conjunction with small dosages of exogenous insulin, a functioning islet allograft can result in near-normalizatio n of blood glucose levels and significant improvement in HbA(1c). The occurrence of severe hypoglycemic episodes observed for patients in th e Diabetes Control and Complications Trial was not observed in recipie nts with functioning islet transplants, despite the continuous need fo r exogenous insulin therapy to sustain normal HbA(1c) over the 6-year follow-up. The significant improvement in metabolic control observed f or the patients described in this study, and the potential to signific antly decrease or halt the progression of diabetic complications, supp ort the continued application of islet allotransplantation as a treatm ent modality for type 1 diabetic patients.