title: Human Pancreatic Islets Isolated From Donors With Elevated HbA1c Levels: Islet Yield and Graft Efficacy.
abstract: The aim of this study was to investigate the effects of elevated donor HbA1c levels (type 2 diabetes, T2D) on the islet yield and functionality postisolation. In this retrospective analysis, donors for islet isolations were classified into two groups: T2D group (HbA1c ≥ 6.5%, n = 18) and normal group (HbA1c < 6.5%, n = 308). Optimum pancreas digestion time (switch time) was significantly higher in the T2D group compared to the normal group (13.7 ± 1.2 vs. 11.7 ± 0.1 min, respectively, p = 0.005). Islet yields were significantly lower in the T2D group compared to the control (T2D vs. control): islet equivalent (IEQ)/g (prepurification 2,318 ± 195 vs. 3,713 ± 114, p = 0.003; postpurification 1,735 ± 175 vs. 2,663 ± 89, p = 0.013) and islet particle number (IPN)/g (prepurification, 2,519 ± 336 vs. 4,433 ± 143, p = 0.001; postpurification, 1,760 ± 229 vs. 2,715 ± 85, p = 0.007). Islets from T2D pancreata had significantly lower viability (T2D vs.
  
  
  METHODS
  91.9 ± 1.6 vs. 94.4 ± 0.3%, p = 0.004) and decreased oxygen consumption rate (ΔOCR) (T2D vs.
  
  
  METHODS
  0.09 ± 0.01 and 0.21 ± 0.03 nmol O2 100 islets(-1) min(-1), p = 0.049). The islets isolated from T2D donor pancreata reversed diabetes in NOD-SCID mice in 9% (2/22) compared to islets from control donor pancreata, which reversed diabetes in 67% (175/260, p < 0.001). In conclusion, this study demonstrates that elevated HbA1c (≥ 6.5%) is associated with impairment of islet function and lower islet yield; however, these islets could not be suitable for clinical applications.
authors.affiliation: Department of Diabetes and Metabolic Diseases Research, Beckman Research Institute of the City of Hope, Duarte, CA, USA.
authors.forename: Meirigeng
authors.initials: M
authors.lastname: Qi
authors.forename: Brian
authors.initials: B
authors.lastname: McFadden
authors.forename: Luis
authors.initials: L
authors.lastname: Valiente
authors.forename: Keiko
authors.initials: K
authors.lastname: Omori
authors.forename: Shiela
authors.initials: S
authors.lastname: Bilbao
authors.forename: Jemily
authors.initials: J
authors.lastname: Juan
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Rawson
authors.forename: Alina R
authors.initials: AR
authors.lastname: Oancea
authors.forename: Stephen
authors.initials: S
authors.lastname: Scott
authors.forename: Indu
authors.initials: I
authors.lastname: Nair
authors.forename: Kevin
authors.initials: K
authors.lastname: Ferreri
authors.forename: Yoko
authors.initials: Y
authors.lastname: Mullen
authors.forename: Donald
authors.initials: D
authors.lastname: Dafoe
authors.forename: Mohamed
authors.initials: M
authors.lastname: Ei-Shahawy
authors.forename: Fouad
authors.initials: F
authors.lastname: Kandeel
authors.forename: Ismail H
authors.initials: IH
authors.lastname: Al-Abdullah
mesh_terms: D000328:Adult; D000818:Animals; D002470:Cell Survival; D003921:Diabetes Mellitus, Experimental / Q000628:therapy; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005947:Glucose / Q000494:pharmacology; D006442:Glycated Hemoglobin / Q000032:analysis*; D006801:Humans; D007515:Islets of Langerhans / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D016381:Islets of Langerhans Transplantation; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D010101:Oxygen Consumption / Q000187:drug effects; D014019:Tissue Donors; D014183:Transplantation, Heterologous
chemical_list: D005947:Glucose; D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human