Sustained beta cell apoptosis in patients with long-standing type 1 diabetes: indirect evidence for islet regeneration?
Open accessAbstract
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.
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The results support histological evidence that occasional insulin-producing beta cells are visible in most pancreas samples from people with long-duration type 1 diabetes.
“These results support the histological data(3; 16) that occasional insulin-producing beta cells are visible in most histological pancreas samples of people with long duration T1D.”
From Most people with long-duration type 1 diabetes in a large population-based study are insulin microsecretors (2015) · cites this paper as [16]
Insufficient β-cell mass can cause insulin insufficiency and diabetes.
“Inadequate β-cell mass can lead to insulin insufficiency and diabetes.”
From Expansion of β-cell mass in response to pregnancy (2010) · cites this paper as [7]
People with type 1 or type 2 diabetes have reduced β-cell mass and increased β-cell apoptosis, with loss exceeding growth.
“Indeed, individuals with either type 1 or type 2 diabetes show decreases in β-cell mass and increases in β-cell apoptosis, outweighing that of β-cell growth [6,7].”
From Expansion of β-cell mass in response to pregnancy (2010) · cites this paper as [7]
Pancreata from people with long-standing type 1 diabetes show measurable β-cell mass and evidence of β-cell apoptosis.
“Intriguingly, pancreata from individuals with long-standing type 1 diabetes displayed not only measurable β-cell mass, but also evidence of β-cell apoptosis [7].”
From Expansion of β-cell mass in response to pregnancy (2010) · cites this paper as [7]
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Self-citation
- Authors
- Meier, J. J., Bhushan, A., Butler, A. E., Rizza, R. A., & Butler, P. C.
- Affiliations
- University of California, Los Angeles (US)
- Mayo Clinic (US)
- Corresponding author
- Butler, P. C.
- Venue
- Diabetologia
- Published
- 2005-10-05
- Volume
- 48
- Issue
- 11
- Pages
- 2221-2228
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2149895222
- Cited by
- 493
- References
- 39
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 18 · 2023: 11 · 2022: 17 · 2021: 18 · 2020: 13 · 2019: 23 · 2018: 17 · 2017: 19 · 2016: 24 · 2015: 33 · 2014: 23 · 2013: 30 · 2012: 36
- FWCI
- 30.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Larry L. Hillblom Foundation
- Deutsche Forschungsgemeinschaft
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 29953, DK68763, R01DK068763, DK 59567)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- type 1 diabetes, beta-cell apoptosis, beta cell regeneration, islet regeneration, beta-cell proliferation, periductal fibrosis, chronic inflammation, macrophages, T cells, glucotoxicity, autoimmunity, beta-cell death, disease duration, blood glucose
- MeSH terms
- Adolescent, Adult, Aged, Blood Glucose, Cell Count, Diabetes Mellitus, Type 1, Female, Fibrosis, Humans, Macrophages, Male, Middle Aged, Pancreas, Regeneration, T-Lymphocytes, Case-Control Studies, Apoptosis, CD3 Complex, Insulin-Secreting Cells, In Vitro Techniques
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