Correlation between β cell mass and glycemic control in type 1 diabetic recipients of islet cell graft

Abstract

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 β cell number help standardize metabolic outcome. Nonuremic C-peptide-negative patients received an intraportal graft with 0.5–5.0 × 10⁶ β 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-peptide >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 × 10⁶ β cells per kgBW versus 0 of 5 with lower number. The nine patients with C-peptide >1 ng/ml and glycemia coefficient of variation of 2 × 10⁶ β cells per kgBW. Of the 20 recipients of at least one graft with >2 × 10⁶ β cells per kgBW, 17 maintained graft function and metabolic control up to PT month 12. At PT month 12, β 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 β cell number.