期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 103, 期 46, 页码 17444-17449出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0608141103
关键词
diabetes; islet transplantation; prevention; type 1 diabetes
Islet grafts can induce insulin independence in type 1 diabetic patients, but their function is variable with only 10% insulin indepence after 5 years. We investigated whether cultured grafts with defined beta cell number help standardize metabolic outcome. Nonuremic C-peptide-negative patients received an intraportal graft with 0.5-5.0 x 10(6) beta cells per kilogram of body weight (kgBW) under antithymocyte globulin and mycophenolate mofetil plus tacrolimus. Metabolic outcome at posttransplant (PT) month 2 was used to decide on a second graft under maintenance mycophenolate mofetil/tacrolimus. Graft function was defined by C-pepticle > 0.5 ng/ml and reduced insulin needs, metabolic control by reductions in HbA(1c), glycemia coefficient of variation, and hypoglycemia. At PT month 2, graft function was present in 16 of 17 recipients of > 2 x 10(6) beta cells per kgBW versus 0 of 5 with lower number. The nine patients with C-pepticle > 1 ng/ml and glycemia coefficient of variation of < 25% did not receive a second graft; five of them were insulin-independent until PT month 12. The 12 others received a second implant; it achieved insulin-independence at PT month 12 when the first and second graft contained > 2 x 10(6) beta cells per kgBW. Of the 20 recipients of at least one graft with > 2 x 10(6) beta cells per kgBW, 17 maintained graft function and metabolic control up to PT month 12. At PT month 12, 13 cell function in insulin-independent patients ranged around 25% of age-matched control values. Thus, 1-year metabolic control can be reproducibly achieved and standardized by cultured islet cell grafts with defined 13 cell number.
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