Prevention of type 1 diabetes

A. Rabinovitch, Jay S Skyler

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

This article discusses type 1 diabetes mellitus, which results from insulin deficiency caused by autoimmune destruction of the insulin-producing β-cells in the pancreatic islets of Langerhans. The autoimmune response against islet β-cells is believed to result from a disorder of immunoregulation. According to this concept, T lymphocytes (T cells) autoreactive to certain β-cell constituents exist normally but are restrained by regulatory (suppressor) T cells. Activation of β-cell autoreactive T cells together with deficient regulatory T cell responses is believed to result in clonal expansion of autoreactive T cells, and these cells may elicit a cascade of β-antigen specific (T cell) immune and nonspecific inflammatory responses that destroy islet β-cells. Islet β- cells autoreactive T cells seem to secrete type 1 cytokines, whereas regulatory T cells may secrete type 2 and type 3 cytokines; therefore, type 1 diabetes may result from a relative dominance of type 1 cytokines over type 2 and type 3 cytokines. These concepts derive mainly from studies in animal models with spontaneous autoimmune diabetes, and the evidence in humans with type 1 diabetes is sparse. Nevertheless, the concept of type 1 diabetes as a disorder of immunoregulation has spurred clinical trials of diabetes prevention based on strategies directed at diverting the immune response from autoimmunity to self-tolerance, for example, by administration of β-cell autoantigens, and by attempting to tip the immune balance in favor of the production or action of type 2 and type 3 cytokines over type 1 cytokines.

Original languageEnglish
Pages (from-to)739-755
Number of pages17
JournalMedical Clinics of North America
Volume82
Issue number4
DOIs
StatePublished - Aug 8 1998
Externally publishedYes

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Type 1 Diabetes Mellitus
Islets of Langerhans
Cytokines
T-Lymphocytes
Regulatory T-Lymphocytes
Autoimmunity
Insulin
Self Tolerance
Animal Models
Clinical Trials
Antigens

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Prevention of type 1 diabetes. / Rabinovitch, A.; Skyler, Jay S.

In: Medical Clinics of North America, Vol. 82, No. 4, 08.08.1998, p. 739-755.

Research output: Contribution to journalArticle

Rabinovitch, A. ; Skyler, Jay S. / Prevention of type 1 diabetes. In: Medical Clinics of North America. 1998 ; Vol. 82, No. 4. pp. 739-755.
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