Immune intervention for type 1 diabetes mellitus

Authors

  • J. S. Skyler

    1. Division of Endocrinology, Diabetes and Metabolism; and Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL, USA
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  • Disclosures: JSS is Chairman of Type 1 Diabetes TrialNet, a clinical trials network conducting multiple studies designed to interrupt the type 1 diabetes disease process. Also, recipient of grant support from Bayhill Therapeutics and Osiris Therapeutics. The author serves on the Board of Directors of Amylin Pharmaceuticals, and chairs the Type 1 Diabetes Advisory Board for sanofi-aventis.

  • Endorsed by the International Conference on ATTD organized by Kenes International.

Jay S. Skyler,
Division of Endocrinology, Diabetes, and Metabolism; and Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL, USA
Tel.: 305-243-6146
Fax: 305-243-4484
Email: jskyler@miami.edu

Abstract

The major form of type 1 diabetes (T1D) is characterised by immune-mediated pancreatic islet β-cell destruction, and has also been called type 1A diabetes to distinguish it from idiopathic forms of islet β-cell loss. Since the first demonstration of islet cell antibodies in 1974, the concept has been that this form of diabetes is autoimmune in nature. The commonly accepted concept is that antibodies (representing the humoral arm of the immune system) do not mediate the β-cell destruction but rather serve as markers of that destruction, while the cellular arm of the immune system, specifically T-lymphocytes, mediate the β-cell destruction. Yet, the T-lymphocytes do not act alone. They receive help in initiating the response from antigen-presenting cells such as dendritic cells and macrophages, and appear to receive help also from B-lymphocytes. In addition, the initial immune response engenders secondary and tertiary responses – involving the whole immunological army – which collectively result in impairment of β-cell function, progressive destruction of β-cells, and consequent development of type 1A diabetes. The process is insidious and may evolve over many years, with the overt expression of clinical symptoms becoming apparent only when most β-cells have been destroyed. Yet, the process clearly evolves at different speeds – much more rapidly in young children, much more slowly in older individuals. And, although it has been thought that ultimately there is complete β-cell destruction, several studies have now demonstrated some degree of persistent β-cell function or existence (at autopsy) in long-standing T1D. A major focus of investigation in T1D is the preservation of β-cell function (and, it is hoped, of β-cells themselves), in the expectation that continuing endogenous insulin secretion will contribute towards better glycaemic control, reduce episodes of severe hypoglycaemia, and slow the development of complications such as retinopathy and nephropathy. Thus, there have been many studies designed to interdict the T1D disease process, mostly by altering the immune system, both during the stage of evolution of the disease and at the time of disease onset. This chapter of the Yearbook of Advanced Technology and Treatments in Diabetes reviews the key papers that have appeared in this field between July 2009 and June 2010. Articles selected were confined to studies in human beings. All immune intervention studies reported in this time frame were included. In addition, the author selected other relevant articles dealing with mechanisms, markers, triggers, and pathology of human type 1 diabetes.

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