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Diabetologia. 2019 Apr;62(4):567-577. doi: 10.1007/s00125-019-4822-4. Epub 2019 Feb 14.

Beta cells in type 1 diabetes: mass and function; sleeping or dead?

Oram RA1,2,3, Sims EK4,5, Evans-Molina C6,7,8,9.

Author information

1
RILD Level 3, Institute of Biomedical and Clinical Science, University of Exeter Medical School, Royal Devon and Exeter Hospital, Barrack Road, Exeter, EX2 5DW, UK. R.Oram@exeter.ac.uk.
2
NIHR Exeter Clinical Research Facility, University of Exeter Medical School, Exeter, UK. R.Oram@exeter.ac.uk.
3
The Academic Renal Unit, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK. R.Oram@exeter.ac.uk.
4
Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA.
5
The Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA.
6
Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA. cevansmo@iu.edu.
7
The Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA. cevansmo@iu.edu.
8
Department of Medicine, Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN, 46202, USA. cevansmo@iu.edu.
9
Roudebush VA Medical Center, Indianapolis, IN, USA. cevansmo@iu.edu.

Abstract

Histological analysis of donor pancreases coupled with measurement of serum C-peptide in clinical cohorts has challenged the idea that all beta cells are eventually destroyed in type 1 diabetes. These findings have raised a number of questions regarding how the remaining beta cells have escaped immune destruction, whether pools of 'sleeping' or dysfunctional beta cells could be rejuvenated and whether there is potential for new growth of beta cells. In this Review, we describe histological and in vivo evidence of persistent beta cells in type 1 diabetes and discuss the limitations of current methods to distinguish underlying beta cell mass in comparison with beta cell function. We highlight that evidence for new beta cell growth in humans many years from diagnosis is limited, and that this growth may be very minimal if at all present. We review recent contributions to the debate around beta cell abnormalities contributing to the pathogenesis of type 1 diabetes. We also discuss evidence for restoration of beta cell function, as opposed to mass, in recent-onset type 1 diabetes, but highlight the absence of data supporting functional recovery in the setting of long-duration diabetes. Finally, future areas of research are suggested to help resolve the source and phenotype of residual beta cells that persist in some, but not all, people with type 1 diabetes.

KEYWORDS:

Beta cell function; Beta cell mass; C-peptide; Network for Pancreatic Organ Donors with Diabetes; Proinsulin; Review; Type 1 diabetes

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