β-cell Mass in Nondiabetic Autoantibody-Positive Subjects: An Analysis Based on the Network for Pancreatic Organ Donors Database.

Abstract

Little information is available about β-cell mass in antibody-positive (Ab+) nondiabetic subjects. We have investigated whether the publicly available virtual slides of the Network for Pancreatic Organ Donors with Diabetes (nPOD) project can be used to assess β-cell mass and distribution in nondiabetic antibody-negative (Ab−) and antibody-positive (Ab+) subjects and in patients with recent-onset type 1 diabetes (T1D). We developed a semi-automated quantification method and applied it to 415 insulin-stained slides from 69 Ab− subjects, 101 slides from 18 Ab+ subjects, and 46 slides from eight recent-onset (<3 y) T1D subjects. Among these subjects, 48, 17, and seven had an available pancreatic mass, respectively, and were used for the quantification of β-cell mass. In Ab− subjects, the β-cell and endocrine mass were 0.66 ± 0.42 and 1.0 ± 0.65 g, respectively. Nonexocrine tissue represented 29% of pancreatic area, a proportion that increased with age. Proportional β-cell area relative to total pancreatic area was higher in the tail compared with head (0.83 vs 0.71%; P < .001). In Ab+ subjects, β-cell mass and β-cell area were similar to those of Ab− individuals, whereas these parameters were dramatically decreased in recent-onset T1D patients. The virtual slides of the nPOD project can be used for quantification projects. In Ab+ nondiabetic subjects, the β-cell mass was not decreased. However, as this cohort is largely composed of donors from the general population, with a single autoantibody, future studies with a larger number of donors with multiple autoantibodies and predisposing human leucocyte antigen genes are required to better define the dynamics of β-cell destruction in the preclinical phases of T1D.