Marc Diedisheim1, Roberto Mallone1, Christian Boitard1, Etienne Larger1. 1. CNRS UMR8104, INSERM U1016, Institut Cochin, Faculté de Médecine (M.D., R.M., C.B., E.L.), Université Paris Descartes Sorbonne Paris Cité, 75014 Paris, France; Assistance Publique Hôpitaux de Paris, Service de Diabétologie and Département Hospitalo-Universitaire "AUTHORS" (R.M., C.B., E.L.), Cochin Hospital, 75014 Paris, France.
Abstract
CONTEXT: Little information is available about β-cell mass in antibody-positive (Ab+) nondiabetic subjects. OBJECTIVE: 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). SUBJECTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.
CONTEXT: Little information is available about β-cell mass in antibody-positive (Ab+) nondiabetic subjects. OBJECTIVE: 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). SUBJECTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Authors: Carol J Lam; Daniel R Jacobson; Matthew M Rankin; Aaron R Cox; Jake A Kushner Journal: J Clin Endocrinol Metab Date: 2017-08-01 Impact factor: 5.958
Authors: Carla J Greenbaum; Cate Speake; Jeffrey Krischer; Jane Buckner; Peter A Gottlieb; Desmond A Schatz; Kevan C Herold; Mark A Atkinson Journal: Diabetes Date: 2018-05-16 Impact factor: 9.461