Dimorphic histopathology of long-standing childhood-onset diabetes
Open accessAbstract
Aims/hypothesis Childhood diabetes is thought to usually result from autoimmune beta cell destruction (type 1A) with eventual total loss of beta cells. Analysis of C-peptide in children characterised at diabetes onset for autoantibodies shows heterogeneous preservation of insulin secretion in long-standing diabetes. The aim of this study was to characterise the pancreases of childhood-onset diabetes in order to define the pathological basis of this heterogeneity. Methods We evaluated 20 cadaveric organ donor pancreases of childhood-onset long-term patients for disease heterogeneity and obtained corresponding C-peptide measurements. Results Pancreases from the majority of cadaveric donors contained only insulin-deficient islets (14 of 20). The remaining six patients (30%) had numerous insulin-positive cells within at least some islets, with two different histological patterns. Pattern A (which we would associate with type 1A diabetes) had lobular retention of areas with 'abnormal' beta cells producing the apoptosis inhibitor survivin and HLA class I. In pattern B, 100% of all islets contained normal-appearing but quantitatively reduced beta cells without survivin or HLA class I. Conclusions/interpretation Our data demonstrate that C-peptide secretion in long-standing diabetic patients can be explained by two different patterns of beta cell survival,possibly reflecting different subsets of type 1 diabetes.
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A third to half of Hispanic and African American children seem to have a form of type 1 diabetes without islet autoantibodies, and with pancreatic histology showing a lack of islets and complete loss of β cells-ie, pseudoatrophic islets.
“For example, a third to half of Hispanic and African American children seem to have a form of type 1 diabetes without islet autoantibodies, and with pancreatic histology showing a lack of islets and complete loss of β cells—ie, pseudoatrophic islets.42”
From Type 1 diabetes (2014) · cites this paper as [42]
The Introduction (page unavailable) reports approximately 15%, not one-third to one-half, of children presenting with new-onset diabetes as autoantibody-negative in association with Hispanic and African-American ancestry. More decisively, the Results and Discussion (pages unavailable) say the two African-American and one Hispanic donors with the distinct pattern retained beta cells in every islet; they did not have the insulin-deficient islets described in the claim. (LLM, conf=0.88)
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Experimental — accuracy not yet measuredType 1B (idiopathic) diabetes represents the remainder of type 1 diabetes cases whose specific pathogenesis remains unclear.
“and type 1B (idiopathic) diabetes, representing the remainder whose specific pathogenesis remains unclear.42”
From Type 1 diabetes (2014) · cites this paper as [42]
The Introduction (page unavailable) says most childhood-onset diabetes is immune-mediated type 1A and identifies other, less well-characterised forms. The Discussion (page unavailable) calls for further study of the causes of a distinct histological pattern. Neither passage identifies those cases as type 1B (idiopathic) or says they constitute the remainder of type 1 diabetes cases. (LLM, conf=0.79)
Experimental — accuracy not yet measuredNot all patients with type 1 diabetes have immunological characteristics, leading to proposed classifications of type 1A (autoimmune) diabetes and type 1B (idiopathic) diabetes.
“However, not all patients with type 1 diabetes have these characteristics, leading to proposed classifications of type 1A (autoimmune) diabetes,41 for the 70–90% of patients with type 1 disease that have immunological, self-reactive autoantibodies, and type 1B (idiopathic) diabetes, representing the remainder whose specific pathogenesis remains unclear.42”
From Type 1 diabetes (2014) · cites this paper as [42]
The Introduction reports that about 15% of children presenting with new-onset diabetes produce no islet autoantibodies, and the Discussion says the causes of some other forms of childhood-onset diabetes need further study. The paper does not identify this entire remainder as type 1B (idiopathic) diabetes; it also discusses other possible forms, including type 2 and monogenic diabetes. No page numbers are available in our copy. (LLM, conf=0.83)
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Research works printed but not linked: 1
- Foulis AK, Liddle CN, Farquharson JA, Richmond JA, Weir RS (1986) The histopathology of the pancreas in type 1 (insulin- dependent) diabetes mellitus: a 25-year review of deaths in patients under 20 years of age in the United Kingdom. Diabetologia 29:267-274
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- Authors
- Gianani, R., Campbell-Thompson, M., Sarkar, S. A., Wasserfall, C., Pugliese, A., Solis, J. M., Kent, S. C., Hering, B. J., West, E., Steck, A., Bonner-Weir, S., Atkinson, M. A., Coppieters, K., von Herrath, M., & Eisenbarth, G. S.
- Affiliations
- University of Colorado Denver (US)
- University of Florida (US)
- Brigham and Women's Hospital (US)
- University of Minnesota (US)
- La Jolla Institute for Immunology (US)
- Corresponding author
- Gianani, R.
- ORCID
- Venue
- Diabetologia
- Published
- 2010-01-09
- Volume
- 53
- Issue
- 4
- Pages
- 690-698
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2061159176
- Cited by
- 158
- References
- 0
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 2 · 2023: 6 · 2022: 5 · 2021: 8 · 2020: 8 · 2019: 7 · 2018: 6 · 2017: 6 · 2016: 14 · 2015: 12 · 2014: 19 · 2013: 15 · 2012: 19
- FWCI
- 10.62
- Type
- journal article
- Language
- en
- Update notices
- correction (2010-06-05)
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- Funders
- National Institutes of Health (DK32083)
- National Institute of Diabetes and Digestive and Kidney Diseases (K01DK080193, P30DK057516, DK080193, DK32083)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- childhood-onset diabetes, beta-cell survival, beta-cell apoptosis, C-peptide secretion, survivin, HLA class I, pancreatic histopathology, autoantibodies, beta cell destruction
- MeSH terms
- Adolescent, Adult, Autoantibodies, C-Peptide, Child, Child, Preschool, Diabetes Mellitus, Type 1, Female, Histocompatibility Testing, HLA-DR Antigens, Humans, Hyperinsulinism, Male, Middle Aged, Pancreas, Sex Characteristics, Tissue Donors, Age of Onset, Insulin-Secreting Cells
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