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Expansion of Exocrine and Endocrine Pancreas with Incretin Therapy

posted 31 May 2013, 16:44 by Amir H Sam   [ updated 31 May 2013, 17:03 ]
Background: GLP-1 has anti-apoptotic and pro-proliferative actions. In beta cells, this could be beneficial; however such an effect has not yet been demonstrated in vivo in humans. In the exocrine pancreas, this could potentially be harmful.

Clinical question: What is the effect of incretin treatments (GLP-1 mimetics and DPP-4 inhibitors) on the endocrine and exocrine human pancreas?

Study design: Histological examination of pancreata from organ donors. Three groups were compared: people with diabetes treated with an incretin for more than 1 year, people with diabetes not treated with an incretin, and people without diabetes (Diabetes. 2013 Mar 22. [Epub ahead of print])

Findings: There was an expansion of both endocrine and exocrine tissue in patients treated with an incretin compared to the other 2 groups. This included 1) increased beta cell mass, 2) marked alpha cell hyperplasia, including one glucagonoma, and alpha cells growing into the pancreatic ducts; the authors suggest these could block ducts and lead to pancreatitis. 3) increased premalignant pancreatic intraepithelial neoplasia lesions.

Imperial Centre for Endocrinology (ICE) views: This study has several limitations: 1) The groups were poorly matched: patients with diabetes who were not receiving an incretin were younger, more likely to be female, and some patients may have had type 1 diabetes. 2) Seven out of eight patients treated with an incretin were on DPP-4 inhibitors. It is unclear if any findings apply to both DPP-4 inhibitors and GLP-1 mimetics. 3) Duration of incretin therapy was not provided; a causative link between incretin treatment and tumorogenesis seems less likely if treatment was short term. 4) Critical illness and prolonged life support leads to changes in pancreatic histology which could confound findings. 

Nevertheless, this paper raises important questions, some of which will hopefully be answered by large long-term studies. In the meantime, incretin therapy should continue to be considered on a case-by-case basis, as is currently our practice.