title: Islet Oxygen Consumption Rate (OCR) Dose Predicts Insulin Independence in Clinical Islet Autotransplantation.
abstract: BACKGROUND
  Reliable in vitro islet quality assessment assays that can be performed routinely, prospectively, and are able to predict clinical transplant outcomes are needed. In this paper we present data on the utility of an assay based on cellular oxygen consumption rate (OCR) in predicting clinical islet autotransplant (IAT) insulin independence (II). IAT is an attractive model for evaluating characterization assays regarding their utility in predicting II due to an absence of confounding factors such as immune rejection and immunosuppressant toxicity.
  
  
  METHODS
  Membrane integrity staining (FDA/PI), OCR normalized to DNA (OCR/DNA), islet equivalent (IE) and OCR (viable IE) normalized to recipient body weight (IE dose and OCR dose), and OCR/DNA normalized to islet size index (ISI) were used to characterize autoislet preparations (n = 35). Correlation between pre-IAT islet product characteristics and II was determined using receiver operating characteristic analysis.
  
  
  RESULTS
  Preparations that resulted in II had significantly higher OCR dose and IE dose (p<0.001). These islet characterization methods were highly correlated with II at 6-12 months post-IAT (area-under-the-curve (AUC) = 0.94 for IE dose and 0.96 for OCR dose). FDA/PI (AUC = 0.49) and OCR/DNA (AUC = 0.58) did not correlate with II. OCR/DNA/ISI may have some utility in predicting outcome (AUC = 0.72).
  
  
  CONCLUSIONS
  Commonly used assays to determine whether a clinical islet preparation is of high quality prior to transplantation are greatly lacking in sensitivity and specificity. While IE dose is highly predictive, it does not take into account islet cell quality. OCR dose, which takes into consideration both islet cell quality and quantity, may enable a more accurate and prospective evaluation of clinical islet preparations.
authors.affiliation: Institute for Cellular Transplantation, Department of Surgery, University of Arizona, Tucson, Arizona, United States of America; Department of Surgery, University of Minnesota, Minneapolis, Minnesota, United States of America; Schulze Diabetes Institute, Minneapolis, Minnesota, United States of America.
authors.forename: Klearchos K
authors.initials: KK
authors.lastname: Papas
authors.affiliation: Department of Surgery, University of Minnesota, Minneapolis, Minnesota, United States of America; Schulze Diabetes Institute, Minneapolis, Minnesota, United States of America.
authors.forename: Melena D
authors.initials: MD
authors.lastname: Bellin
authors.affiliation: Department of Surgery, University of Minnesota, Minneapolis, Minnesota, United States of America; Schulze Diabetes Institute, Minneapolis, Minnesota, United States of America.
authors.forename: David E R
authors.initials: DE
authors.lastname: Sutherland
authors.affiliation: Department of Surgery, University of Minnesota, Minneapolis, Minnesota, United States of America; Schulze Diabetes Institute, Minneapolis, Minnesota, United States of America.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Suszynski
authors.affiliation: Institute for Cellular Transplantation, Department of Surgery, University of Arizona, Tucson, Arizona, United States of America; Department of Surgery, University of Minnesota, Minneapolis, Minnesota, United States of America; Schulze Diabetes Institute, Minneapolis, Minnesota, United States of America.
authors.forename: Jennifer P
authors.initials: JP
authors.lastname: Kitzmann
authors.affiliation: Department of Surgery, University of Minnesota, Minneapolis, Minnesota, United States of America; Schulze Diabetes Institute, Minneapolis, Minnesota, United States of America.
authors.forename: Efstathios S
authors.initials: ES
authors.lastname: Avgoustiniatos
authors.affiliation: Institute for Cellular Transplantation, Department of Surgery, University of Arizona, Tucson, Arizona, United States of America.
authors.forename: Angelika C
authors.initials: AC
authors.lastname: Gruessner
authors.affiliation: Institute for Cellular Transplantation, Department of Surgery, University of Arizona, Tucson, Arizona, United States of America; Department of Surgery, University of Minnesota, Minneapolis, Minnesota, United States of America; Schulze Diabetes Institute, Minneapolis, Minnesota, United States of America.
authors.forename: Kathryn R
authors.initials: KR
authors.lastname: Mueller
authors.affiliation: Department of Surgery, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Beilman
authors.affiliation: Department of Surgery, University of Minnesota, Minneapolis, Minnesota, United States of America; Schulze Diabetes Institute, Minneapolis, Minnesota, United States of America.
authors.forename: Appakalai N
authors.initials: AN
authors.lastname: Balamurugan
authors.affiliation: Department of Surgery, University of Minnesota, Minneapolis, Minnesota, United States of America; Schulze Diabetes Institute, Minneapolis, Minnesota, United States of America.
authors.forename: Gopalakrishnan
authors.initials: G
authors.lastname: Loganathan
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
authors.forename: Clark K
authors.initials: CK
authors.lastname: Colton
authors.affiliation: The Transplant Institute, Beth Israel Deaconess Medical Center (BIDMC), Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Maria
authors.initials: M
authors.lastname: Koulmanda
authors.affiliation: Joslin Diabetes Center, Boston, Massachusetts, United States of America.
authors.forename: Gordon C
authors.initials: GC
authors.lastname: Weir
authors.affiliation: Department of Surgery, University of Minnesota, Minneapolis, Minnesota, United States of America; Schulze Diabetes Institute, Minneapolis, Minnesota, United States of America.
authors.forename: Josh J
authors.initials: JJ
authors.lastname: Wilhelm
authors.affiliation: Information Science, City of Hope, Duarte, California, United States of America.
authors.forename: Dajun
authors.initials: D
authors.lastname: Qian
authors.affiliation: Information Science, City of Hope, Duarte, California, United States of America.
authors.forename: Joyce C
authors.initials: JC
authors.lastname: Niland
authors.affiliation: Department of Surgery, University of Minnesota, Minneapolis, Minnesota, United States of America; Schulze Diabetes Institute, Minneapolis, Minnesota, United States of America.
authors.forename: Bernhard J
authors.initials: BJ
authors.lastname: Hering
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001835:Body Weight; D002462:Cell Membrane / Q000378:metabolism; D004247:DNA / Q000737:chemistry; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000737:chemistry; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism*; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008297:Male; D010101:Oxygen Consumption; D010180:Pancreatectomy; D010195:Pancreatitis / Q000628:therapy; D012372:ROC Curve; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D007328:Insulin; D004247:DNA