Correlation between beta cell mass and glycemic control in type 1 diabetic recipients of islet cell graft.
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.
Keymeulen
Bart
B
Diabetes Research Center and Academisch Ziekenhuis, Vrije Universiteit Brussel, B-1090 Brussels, Belgium.
Gillard
Pieter
P
Mathieu
Chantal
C
Movahedi
Babak
B
Maleux
Geert
G
Delvaux
Georges
G
Ysebaert
Dirk
D
Roep
Bart
B
Vandemeulebroucke
Evy
E
Marichal
Miriam
M
In 't Veld
Peter
P
Bogdani
Marika
M
Hendrieckx
Christel
C
Gorus
Frans
F
Ling
Zhidong
Z
van Rood
Jon
J
Pipeleers
Daniel
D
D000293:Adolescent; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000473:pathology* / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009929:Organ Size; D016035:Pancreas Transplantation / Q000009:adverse effects; D015996:Survival Rate; D016896:Treatment Outcome
D001786:Blood Glucose; D007328:Insulin