Correlation Between Beta Cell Mass and Glycemic Control in Type 1 Diabetic Recipients of Islet Cell Graft

Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17444-9. doi: 10.1073/pnas.0608141103. Epub 2006 Nov 7.

Abstract

Islet grafts can induce insulin independence in type 1 diabetic patients, but their function is variable with only 10% insulin independence 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 (kg BW) 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 x 10(6) beta cells per kg BW versus 0 of 5 with lower number. The nine patients with C-peptide >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 kg BW. Of the 20 recipients of at least one graft with >2 x 10(6) beta cells per kg BW, 17 maintained graft function and metabolic control up to PT month 12. At PT month 12, beta 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 beta cell number.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Blood Glucose / metabolism*
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / pathology*
  • Diabetes Mellitus, Type 1 / surgery
  • Female
  • Follow-Up Studies
  • Graft Survival
  • Humans
  • Insulin / metabolism
  • Insulin Secretion
  • Islets of Langerhans / metabolism
  • Islets of Langerhans / pathology*
  • Islets of Langerhans / surgery
  • Male
  • Middle Aged
  • Organ Size
  • Pancreas Transplantation* / adverse effects
  • Survival Rate
  • Treatment Outcome

Substances

  • Blood Glucose
  • Insulin