The Discovery of Type 1 Diabetes
Open accessAbstract
The etiological heterogeneity of idiopathic diabetes has been recognized for 25 years, and subdivision into type 1 and type 2 diabetes is fundamental to the way we think about the disease. Review of the literature suggests that the concept of type 1 diabetes as an immunemediated disease emerged rapidly over the period from 1974 to 1976 and showed many of the features of a classic paradigm shift. A few key observations triggered recognition and acceptance of the new paradigm, but the necessary context was provided by scientific developments in areas mainly unrelated to diabetes. The disease paradigm established by 1976 is still widely accepted, and its essential features have been modified only in detail by the revolution in molecular biology that has occurred over the intervening period. Notwithstanding, some of the underlying assumptions remain imprecise, unchallenged, or unconfirmed. Appreciation of the historical origin and subsequent evolution of these fundamental concepts could stimulate critical analysis and help prepare the way for a new paradigm.
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By the end of the 1970s, work led to recognition that immune-mediated loss of insulin-secreting cells was the cause of insulin-dependent diabetes.
“By the end of the 1970s, this work led to the recognition that immune-mediated loss of insulin-secreting cells was the cause of insulin-dependent diabetes3.”
From 100 years of insulin: celebrating the past, present and future of diabetes therapy (2021) · cites this paper as [3]
In “The Road to Autoimmune Diabetes” (page unavailable), Gale describes evidence that converged on an autoimmune paradigm during the 1970s, and “Animal Models of Diabetes” describes immune-mediated models developed in 1976. But the latter section also says viral infection was still thought to account for many cases and describes both immune-mediated and non-immune-mediated forms of type 1 diabetes. The claim overstates the paper by presenting immune-mediated cell loss as the established cause of all insulin-dependent diabetes by the end of the decade. (LLM, conf=0.84)
Experimental — accuracy not yet measuredFranco Bottazzo was the first to successfully visualize islet cell antibodies using indirect immunofluorescence, confirming the presence of antibodies reactive to the islet.
“In a now famous ‘eureka’ moment, in 1974, Franco Bottazzo, a research fellow in Deborah Doniach’s laboratory in London, was the first to successfully visualize islet cell antibodies using indirect immunofluorescence, thereby confirming the presence of antibodies reactive to the islet.”
From 100 years of insulin: celebrating the past, present and future of diabetes therapy (2021) · cites this paper as [3]
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Cites
AUTO-ANTIBODIES IN HASHIMOTO'S DISEASE (LYMPHADENOID GOITRE)
Roitt, I. M., Doniach, D., Campbell, P. N., & Vaughan Hudson, R. (1956) · The Lancet · doi:10.1016/s0140-6736(56)92249-8 · Cited by 575 · see citing works
AUTO-ANTIBODIES IN ADDISON'S DISEASE
Anderson, J. R., Goudie, R. B., Gray, K., & Timbury, G. C. (1957) · The Lancet · doi:10.1016/s0140-6736(57)91687-2 · Cited by 179 · see citing works
INTRINSIC-FACTOR ANTIBODY IN DIABETES MELLITUS
Ungar, B., Stocks, A. E., Martin, F. I. R., Whittingham, S., & Mackay, I. (1967) · The Lancet · doi:10.1016/s0140-6736(67)92064-8 · Cited by 29 · see citing works
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Research works printed but not linked: 7
- Kuhn TS: The Structure of Scientific Revolutions. 2nd ed. Chicago, Univer- sity of Chicago Press, 1970
- Wells HG: Addison's disease with selective destruction of the suprarenal cor- tex. Arch Pathol 10:499-523, 1930
- Sexton C: The Seeds of Time: The Life of Sir Macfarlane Burnet. Oxford, U.K., Oxford University Press, 1991
- Renold AE, Soeldner JS, Steinke J: Immunological studies with homolo- gous and heterologous pancreatic insulin in the cow. In Ciba Foundation Col- loquia: Aetiology of Diabetes and Its Complications. Vol. 15. London, Churchill, 1964, p. 122-139
- Williams RH, Ed. Philadelphia, W.B. Saunders, 1974, p. 502-626
- Burnet M: Self and Not-Self. Cambridge, U.K., Cambridge University Press, 1969 101.
- Weatherall D: Science and the Quiet Art: Medical Research and Patient Care. Oxford, U.K., Oxford University Press, 1995 104.
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100 years of insulin: celebrating the past, present and future of diabetes therapy
Sims, E. K., Carr, A. L. J., Oram, R. A., DiMeglio, L. A., & Evans-Molina, C. (2021) · Nature Medicine · doi:10.1038/s41591-021-01418-2 · Cited by 270 · see citing works
Nutritional risk predictors of β cell autoimmunity and type 1 diabetes at a young age
Virtanen, S. M., & Knip, M. (2003) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/78.6.1053 · Cited by 220 · see citing works
A novel diabetes typology: towards precision diabetology from pathogenesis to treatment
Herder, C., & Roden, M. (2022) · Diabetologia · doi:10.1007/s00125-021-05625-x · Cited by 140 · see citing works
Gale, E. A. M. (2006) · Diabetologia · doi:10.1007/s00125-006-0348-7 · Cited by 71 · see citing works
Self-citation
- Authors
- Gale, E. A. M.
- Affiliations
- University of Bristol (GB)
- Corresponding author
- Gale, Edwin A.M.
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2001-02-01
- Volume
- 50
- Issue
- 2
- Pages
- 217-226
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2094929545
- Cited by
- 157
- References
- 3
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 5 · 2023: 9 · 2022: 10 · 2021: 7 · 2020: 4 · 2019: 4 · 2018: 3 · 2017: 4 · 2016: 4 · 2015: 6 · 2014: 6 · 2013: 6 · 2012: 3
- FWCI
- 5.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Keywords
- type 1 diabetes, type 2 diabetes, etiologic heterogeneity, immunological etiology, history of diabetes research
- MeSH terms
- Animals, Diabetes Mellitus, Type 1, Disease Models, Animal, Endocrinology, Humans, Genetic Predisposition to Disease, History, 19th Century, History, 20th Century
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