title: Minimal functional β-cell mass in intraportal implants that reduces glycemic variability in type 1 diabetic recipients.
abstract: OBJECTIVE
  Previous work has shown a correlation between β-cell number in cultured islet cell grafts and their ability to induce C-peptide secretion after intraportal implantation in C-peptide-negative type1 diabetic patients. In this cross-sectional study, we examined the minimal functional β-cell mass (FBM) in the implant that induces metabolic improvement.
  
  
  METHODS
  Glucose clamps assessed FBM in 42 recipients with established implants. C-peptide release during each phase was expressed as percentage of healthy control values. Its relative magnitude during a second hyperglycemic phase was most discriminative and therefore selected as a parameter to be correlated with metabolic effects.
  
  
  RESULTS
  Recipients with functioning β-cell implants exhibited average FBM corresponding to 18% of that in normal control subjects (interquartile range 10-33%). Its relative magnitude negatively correlated with HbA1c levels (r = -0.47), daily insulin dose (r = -0.75), and coefficient of variation of fasting glycemia (CVfg) (r = -0.78, retained in multivariate analysis). A correlation between FBM and CVfg <25% appeared from the receiver operating characteristic curve (0.97 [95% CI 0.93-1.00]). All patients with FBM >37% exhibited CVfg <25% and a >50% reduction of their pretransplant CVfg; this occurred in none with FBM <5%. Implants with FBM >18% reduced CVfg from a median pretransplant value of 46 to <25%.
  
  
  CONCLUSIONS
  Glucose clamping assesses the degree of restoration in FBM achieved by islet cell implants. Values >37% of normal control subjects appear needed to reduce glycemic variability in type 1 diabetic recipients. Further studies should examine whether the test can help guide decisions on additional islet cell transplants and on adjusting or stopping immunotherapy.
authors.affiliation: Corresponding author: Bart Keymeulen, bart.keymeulen@uzbrussel.be.
authors.forename: Pieter
authors.initials: P
authors.lastname: Gillard
authors.forename: Robert
authors.initials: R
authors.lastname: Hilbrands
authors.forename: Ursule
authors.initials: U
authors.lastname: Van de Velde
authors.forename: Zhidong
authors.initials: Z
authors.lastname: Ling
authors.forename: Da Hae
authors.initials: DH
authors.lastname: Lee
authors.forename: Ilse
authors.initials: I
authors.lastname: Weets
authors.forename: Frans
authors.initials: F
authors.lastname: Gorus
authors.forename: Christophe
authors.initials: C
authors.lastname: De Block
authors.forename: Leonard
authors.initials: L
authors.lastname: Kaufman
authors.forename: Chantal
authors.initials: C
authors.lastname: Mathieu
authors.forename: Daniel
authors.initials: D
authors.lastname: Pipeleers
authors.forename: Bart
authors.initials: B
authors.lastname: Keymeulen
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000032:analysis / Q000378:metabolism; D002452:Cell Count; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery*; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000502:physiology*; D007515:Islets of Langerhans / Q000378:metabolism; D016381:Islets of Langerhans Transplantation; D008297:Male; D008875:Middle Aged; D011169:Portal Vein
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin
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