Insulitis in human type 1 diabetes: The quest for an elusive lesion
Open accessAbstract
The histopathology of type 1 diabetes is defined by a decreased β-cell mass in association with insulitis, a characteristic lymphocytic infiltration limited to the islets of Langerhans and prominent in early stage disease in children. A cytotoxic T-cell mediated destruction of insulin-producing β-cells is thought to be initiated by an unknown (auto)antigen, leading to the destruction > 75% of β-cell mass at clinical diagnosis. Although considered to be pathognomonic for recent onset disease, insulitis has only been described in approximately 150 cases over the past century. This review describes the quest for this elusive lesion and gives its incidence in various patient subpopulations stratified for age of onset and duration of the disease. It discusses recent new insights into the regenerative capacity of the β-cell mass in the pre-clinical stages of the disease and relates these findings to the inflammatory processes within the islet tissue.
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The presence of a chronic inflammatory infiltrate that affects pancreatic islets at symptomatic onset of type 1 diabetes is the basis of the observation that the disorder results from autoimmune destruction of insulin-secreting pancreatic β cells.
“The presence of a chronic inflammatory infiltrate that affects pancreatic islets at symptomatic onset of type 1 diabetes is the basis of this observation (figure 2).49”
From Type 1 diabetes (2014) · cites this paper as [49]
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“Interestingly, the types of cells that were different were not the same as those that were infiltrating islets.”
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Daryabor, G., Shiri, E. H., Amirghofran, Z., & Kamali‐Sarvestani, E. (2021) · Hepatobiliary & pancreatic diseases international · doi:10.1016/j.hbpd.2021.03.008 · Cited by 6 · see citing works
The dark side of islet vasculature
Veld, P. I. '., & Lammert, E. (2014) · Diabetologia · doi:10.1007/s00125-014-3418-2 · Cited by 6 · see citing works
Casagrande, V., Menini, S., Internò, C., Pugliese, G., Federici, M., & Menghini, R. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1297847 · Cited by 7 · see citing works
Maiorino, M. I., Buzzetti, R., Irace, C., Laviola, L., Napoli, N., Pitocco, D., Esposito, K., & on behalf of LIVE CGM working group (2023) · Endocrine · doi:10.1007/s12020-023-03473-w · Cited by 7 · see citing works
Immunoregulated insulitis and slow-progressing type 1 diabetes after duodenopancreatectomy
Faucher, P., Beuvon, F., Fignani, D., Sebastiani, G., Afonso, G., Zhou, Z., Dousset, B. E., Boîtard, C., Dotta, F., Mallone, R., et al. (2021) · Diabetologia · doi:10.1007/s00125-021-05563-8 · Cited by 7 · see citing works
Veronese-Paniagua, D., & Millman, J. R. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1734431 · Cited by 5 · see citing works
A Historical and Epistemological Review of Type 1 Diabetes Mellitus
Cavalli, E., Nicoletti, G. R. P., & Nicoletti, F. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14144923 · Cited by 4 · see citing works
Understanding the Mechanism of Diabetes Mellitus in a LRBA-Deficient Patient
Hawari, I., Ericsson, J., Kabeer, B. S. A., Chaussabel, D., Al-Sulaiti, A. M., Sharari, S., Maccalli, C., Khan, F. A., & Hussain, K. (2022) · Biology · doi:10.3390/biology11040612 · Cited by 4 · see citing works
Khalifa, A. K., Abdelrahim, D. S., Mekawy, D. M., Hamed, R. M. R., Mohamed, W. R., Ramadan, N. M., Wael, M., Ellackany, R., Albadawi, E. A., & Osman, W. A. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e38932 · Cited by 2 · see citing works
Immunologic and Genetic Factors in Type 1 Diabetes Mellitus
Massoud, A., & Massoud, A. H. (2012) · InTech eBooks · doi:10.5772/48141 · Cited by 1 · see citing works
Hsiao, C.-Y., Shyu, J., Chiang, C.-S., Chou, S.-C., Chu, T.-H., Chen, T.-H., Huang, M.-Y., Hung, W., & Tsai, P.-J. (2026) · Zhōnghuá Pífūkē Yīxué Zázhì · doi:10.4103/ds.ds-d-26-00019 · Cited by 1
Kang, S., Maya, N., MORILLO, M., OUTAR, M., Posgai, A. L., Lamb, D. G., Campbell‐Thompson, M., & Kim, S. (2026) · Diabetologia · doi:10.1007/s00125-026-06742-1 · Cited by 1 · see citing works
Vaitaitis, G., Waid, D., Sharkey, C., Sharkey, S. A., Webb, T. L., Webb, C., & Wagner, D. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1759373 · Cited by 1
Ullsten, S., Espes, D., Quach, M., Fex, M., Sandberg, M., & Carlsson, P. (2020) · Physiological Reports · doi:10.14814/phy2.14444 · Cited by 2 · see citing works
Development of early-stage type 1 diabetes in germ-free interleukin-10 deficient micePreprint
Bobe, A. M., Miyoshi, J., Moore, P. C., Devkota, S., Leone, V., Martinez, K., Theriault, B. R., Musch, M. W., Wasserfall, C. H., Atkinson, M. A., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.04.18.048272 · Cited by 2 · see citing works
“Pancreatic data from T1D donors and murine models support the role of B and T lymphocytes and antigen-presenting cells in disease pathology (In’t Veld, 2011; Magnuson et al., 2014; Walker and von Herrath, 2016).”
ResultJoosten, L., Boss, M., Jansen, T. J. P., Brom, M., Buitinga, M., Aarntzen, E. H. J. G., Eriksson, O., Johansson, L., de Galan, B. E., & Gotthardt, M. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-816386-3.00041-7
Pediatric Diabetes: Review Article
Bavishna, B., Devi, R. U., & Krishnan, S. G. (2019) · Indian Journal of Public Health Research & Development · doi:10.5958/0976-5506.2019.04013.0
New insights into β-cell vulnerability in type 1 diabetes-Lessons from nature.
Murrall, K., Luckett, T., Lekka, C., Hunter, S. L., Agnello, S., Ferris, P., Haxton, E., Flaxman, C. S., Kannan, A., Dun, X.-P., et al. (2026) · Diabetic Medicine · doi:10.1111/dme.70509
From disease heterogeneity to precision therapy in type 1 diabetes mellitus
Nigi, L., Pagano, R., Sarti, F., Sebastiani, G., & Dotta, F. (2026) · Endocrine · doi:10.1007/s12020-026-04637-0
Clinically Relevant Mathematical Model for the BCG-based Treatment Of Type 1 DiabetesPreprint
Lazebnik, T., Bunimovich‐Mendrazitsky, S., & Kiselyov, A. S. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.09.02.458659
- Authors
- In't Veld, P.
- Venue
- Islets
- Publisher
- Informa UK Limited
- Published
- 2011-07
- Volume
- 3
- Issue
- 4
- Pages
- 131-138
- ISSN
- 1938-2014 (ISSN-L)
- 1938-2022
- PMC
- PMC3154446
- OpenAlex
- W3039233428
- Cited by
- 216
- References
- 0
- Citations by year
- 2026: 5 · 2025: 12 · 2024: 10 · 2023: 12 · 2022: 11 · 2021: 19 · 2020: 10 · 2019: 9 · 2018: 14 · 2017: 17 · 2016: 21 · 2015: 26 · 2014: 23 · 2013: 11 · 2012: 15
- FWCI
- 1.66
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Islets (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Fonds Wetenschappelijk Onderzoek
- Vlaamse regering
- 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
- insulitis, type 1 diabetes, beta cell destruction, cytotoxic T lymphocytes, beta cell regeneration, preclinical disease, age of onset, disease duration, autoimmunity
- MeSH terms
- Adolescent, Adult, Child, Child, Preschool, Diabetes Mellitus, Type 1, Humans, Infant, Islets of Langerhans, Lymphocytes, Organ Size, Pancreatitis, Age of Onset, History, 20th Century, History, 21st Century, Young Adult
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