Pancreas Pathology of Latent Autoimmune Diabetes in Adults (LADA) in Patients and in a LADA Rat Model Compared With Type 1 Diabetes

Diabetes. 2020 Apr;69(4):624-633. doi: 10.2337/db19-0865. Epub 2020 Jan 23.


Approximately 10% of patients with type 2 diabetes suffer from latent autoimmune diabetes in adults (LADA). This study provides a systematic assessment of the pathology of the endocrine pancreas of patients with LADA and for comparison in a first rat model mimicking the characteristics of patients with LADA. Islets in human and rat pancreases were analyzed by immunohistochemistry for immune cell infiltrate composition, by in situ RT-PCR and quantitative real-time PCR of laser microdissected islets for gene expression of proinflammatory cytokines, the proliferation marker proliferating cell nuclear antigen (PCNA), the anti-inflammatory cytokine interleukin (IL) 10, and the apoptosis markers caspase 3 and TUNEL as well as insulin. Human and rat LADA pancreases showed differences in areas of the pancreas with respect to immune cell infiltration and a changed ratio between the number of macrophages and CD8 T cells toward macrophages in the islet infiltrate. Gene expression analyses revealed a changed ratio due to an increase of IL-1β and a decrease of tumor necrosis factor-α. IL-10, PCNA, and insulin expression were increased in the LADA situation, whereas caspase 3 gene expression was reduced. The analyses into the underlying pathology in human as well as rat LADA pancreases provided identical results, allowing the conclusion that LADA is a milder form of autoimmune diabetes in patients of an advanced age.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Diabetes Mellitus, Type 1 / pathology*
  • Diabetes Mellitus, Type 2 / pathology
  • Disease Models, Animal
  • Female
  • Humans
  • Latent Autoimmune Diabetes in Adults / pathology*
  • Male
  • Middle Aged
  • Pancreas / pathology*
  • Rats