Human Pancreatic Islets Isolated From Donors With Elevated HbA1c Levels: Islet Yield and Graft Efficacy

Cell Transplant. 2015;24(9):1879-86. doi: 10.3727/096368914X683548. Epub 2014 Aug 5.

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.

Control: 91.9 ± 1.6 vs. 94.4 ± 0.3%, p = 0.004) and decreased oxygen consumption rate (ΔOCR) (T2D vs.

Control: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Cell Survival
  • Diabetes Mellitus, Experimental / therapy
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / pathology*
  • Female
  • Glucose / pharmacology
  • Glycated Hemoglobin A / analysis*
  • Humans
  • Islets of Langerhans / cytology*
  • Islets of Langerhans / metabolism
  • Islets of Langerhans / pathology
  • Islets of Langerhans Transplantation
  • Male
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Middle Aged
  • Oxygen Consumption / drug effects
  • Tissue Donors
  • Transplantation, Heterologous

Substances

  • Glycated Hemoglobin A
  • hemoglobin A1c protein, human
  • Glucose