Sustained beta cell apoptosis in patients with long-standing type 1 diabetes: indirect evidence for islet regeneration?

Diabetologia. 2005 Nov;48(11):2221-8. doi: 10.1007/s00125-005-1949-2. Epub 2005 Oct 5.


Aims/hypothesis: Type 1 diabetes is widely held to result from an irreversible loss of insulin-secreting beta cells. However, insulin secretion is detectable in some people with long-standing type 1 diabetes, indicating either a small population of surviving beta cells or continued renewal of beta cells subject to ongoing autoimmune destruction. The aim of the present study was to evaluate these possibilities.

Materials and methods: Pancreatic sections from 42 individuals with type 1 diabetes and 14 non-diabetic individuals were evaluated for the presence of beta cells, beta cell apoptosis and replication, T lymphocytes and macrophages. The presence and extent of periductal fibrosis was also quantified.

Results: Beta cells were identified in 88% of individuals with type 1 diabetes. The number of beta cells was unrelated to duration of disease (range 4-67 years) or age at death (range 14-77 years), but was higher (p<0.05) in individuals with lower mean blood glucose. Beta cell apoptosis was twice as frequent in type 1 diabetes as in control subjects (p<0.001), but beta cell replication was rare in both groups. The increased beta cell apoptosis in type 1 diabetes was accompanied by both increased macrophages and T lymphocytes and a marked increase in periductal fibrosis (p<0.001), implying chronic inflammation over many years, consistent with an ongoing supply of beta cells.

Conclusions/interpretation: Most people with long-standing type 1 diabetes have beta cells that continue to be destroyed. The mechanisms underlying increased beta cell death may involve both ongoing autoimmunity and glucose toxicity. The presence of beta cells despite ongoing apoptosis implies, by definition, that concomitant new beta cell formation must be occurring, even after long-standing type 1 diabetes. We conclude that type 1 diabetes may be reversed by targeted inhibition of beta cell destruction.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Apoptosis / physiology
  • Blood Glucose / metabolism
  • CD3 Complex
  • Case-Control Studies
  • Cell Count
  • Diabetes Mellitus, Type 1 / etiology
  • Diabetes Mellitus, Type 1 / pathology*
  • Female
  • Fibrosis
  • Humans
  • In Vitro Techniques
  • Insulin-Secreting Cells / pathology*
  • Macrophages / pathology
  • Male
  • Middle Aged
  • Pancreas / physiology*
  • Regeneration*
  • T-Lymphocytes / pathology


  • Blood Glucose
  • CD3 Complex