Modestly increased beta cell apoptosis but no increased beta cell replication in recent-onset type 1 diabetic patients who died of diabetic ketoacidosis

A. E. Butler, R. Galasso, J. J. Meier, R. Basu, R. A. Rizza, P. C. Butler

Research output: Contribution to journalArticle

78 Scopus citations

Abstract

Aims/hypothesis: Type 1 diabetes is characterised by a deficit in beta cell mass thought to be due to immune-mediated increased beta cell apoptosis. Beta cell turnover has not been examined in the context of new-onset type 1 diabetes with diabetic ketoacidosis. Methods: Samples of pancreas were obtained at autopsy from nine patients, aged 12 to 38 years (mean 24.3±3.4 years), who had had type 1 diabetes for less than 3 years before death due to diabetic ketoacidosis. Samples of pancreas obtained at autopsy from nine non-diabetic cases aged 11.5 to 38 years (mean 24.2±3.4 years) were used as control. Fractional beta cell area (insulin staining), beta cell replication (insulin and Ki67 staining) and beta cell apoptosis (insulin and TUNEL staining) were measured. Results: In pancreas obtained at autopsy from recent-onset type 1 diabetes patients who had died of diabetic ketoacidosis, the beta cell deficit varied from 70 to 99% (mean 90%). The pattern of beta cell loss was lobular, with almost all beta cells absent in most pancreatic lobules; islets in lobules not devoid of beta cells had reduced or a near-normal complement of beta cells. Beta cell apoptosis was increased in recent-onset type 1 diabetes, but to a surprisingly modest degree given the marked hyperglycaemia (30 mmol/l), acidosis and presumably high NEFA. Beta cell replication, scattered pancreatic beta cells and beta cells in exocrine ducts were not increased in recent-onset type 1 diabetes. Conclusions/interpretation: These findings do not support the notion of active beta cell regeneration by replication in new-onset type 1 diabetes under conditions of diabetic ketoacidosis. The gluco-lipotoxicity reported in isolated human islets may be less evident in vivo.

Original languageEnglish (US)
Pages (from-to)2323-2331
Number of pages9
JournalDiabetologia
Volume50
Issue number11
DOIs
StatePublished - Nov 1 2007

Keywords

  • Apoptosis
  • Beta cell replication
  • Human
  • Islet degeneration and damage
  • Islets
  • Ketoacidosis
  • Prediction of type 1 diabetes
  • Prevention of type 1 diabetes
  • Recent-onset type 1 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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