Type 1 diabetes mellitus (T1DM) is a chronic condition characterized by autoimmune destruction of the pancreatic β cells; as a consequence, affected individuals are unable to produce insulin and maintain adequate glucose homeostasis.
Daily administration of exogenous insulin has long been the mainstay of the clinical management of patients with T1DM; however, therapeutic use of insulin has a number of drawbacks. Although efforts have been made to address at least some of these problems, novel approaches to the treatment of T1DM are clearly warranted. Over the past decade, increased understanding of the pathogenesis of T1DM, at both the molecular and cellular level, has aided the development of potential noninsulin-based therapies for T1DM. These therapies are diverse in nature and range from stem-cell transplantation to replenish the damaged pancreatic β cells to modulation of the immune response. Other approaches aim to prevent development of T1DM in the first place.
This Focus issue provides an expert overview of noninsulin therapies currently in development or clinical trials, all of which have been identified by leaders in the field as promising strategies for the future management of patients with T1DM.
An NPG library of relevant Research Highlights, Viewpoints, Reviews, Case Studies and Original Research is also provided.
EDITORIAL
A crossroads for diabetes care?
Vicky Heath
doi:10.1038/nrendo.2010.5
Nature Reviews Endocrinology 6, 117 (2010)
RESEARCH HIGHLIGHTS
Selective depletion of B lymphocytes with rituximab preserves β-cell function
Vicky Heath
doi:10.1038/nrendo.2009.279
Nature Reviews Endocrinology 6, 119 (2010)
GLP-1 directs differentiation of human embryonic stem cells
Vicky Heath
doi:10.1038/nrendo.2009.285
Nature Reviews Endocrinology 6, 123 (2010)
REVIEWS
Immunomodulation with microbial vaccines to prevent type 1 diabetes mellitus
Nikolai Petrovsky
doi:10.1038/nrendo.2009.273
Nature Reviews Endocrinology 6, 131-138 (2010)
Improved hygiene has reduced childhood exposure to environmental microbes, a change that could partly explain the increased incidence of autoimmune diseases, such as type 1 diabetes mellitus, now reported in the developed world. Such exposure to microbes seems to promote development of a healthy immune system; in experimental animal models, administration of microbes or their components can inhibit autoimmune diabetes. This finding raises the possibility of a future vaccine against type 1 diabetes mellitus.
Stem cell therapy for type 1 diabetes mellitus
Cristina Aguayo-Mazzucato & Susan Bonner-Weir
doi:10.1038/nrendo.2009.274
Nature Reviews Endocrinology 6, 139-148 (2010)
Clinicians and patients with type 1 diabetes mellitus eagerly await the successful use of stem cell-derived β cells in clinical practice. This Review provides a summary of current strategies to obtain cells which express insulin from different progenitor sources and highlights the main pathways and genes involved, as well as the different approaches for the modulation of the immune response in patients with type 1 diabetes mellitus.
Immune therapy for type 1 diabetes mellitus—what is unique about anti-CD3 antibodies?
Lucienne Chatenoud
doi:10.1038/nrendo.2009.275
Nature Reviews Endocrinology 6, 149-157 (2010)
Immune therapies that induce or, in the case of established type 1 diabetes mellitus (T1DM), restore immune tolerance to target autoantigens hold potential to cure T1DM whilst avoiding the need for chronic immunosuppression. This Review discusses different immune therapies for T1DM and, in particular, focuses on two promising strategies in clinical development—the use of candidate autoantigens and anti-CD3 monoclonal antibodies—that aim to restore immune tolerance.
Blockade of interleukin 1 in type 1 diabetes mellitus
Thomas Mandrup-Poulsen, Linda Pickersgill & Marc Yves Donath
doi:10.1038/nrendo.2009.271
Nature Reviews Endocrinology 6, 158-166 (2010)
Interleukin 1 (IL-1) has important functions in innate and adaptive immunity. Blocking IL-1 action has clinical efficacy in many inflammatory diseases, including type 2 diabetes mellitus. Here, the authors review the mechanisms of IL-1 action that lead to β-cell failure and the rationale for use of IL-1 antagonists in type 1 diabetes mellitus.
PERSPECTIVES
Opinion: Stem cell and gene therapies for diabetes mellitus
Roy Y. Calne, Shu Uin Gan & Kok Onn Lee
doi:10.1038/nrendo.2009.276
Nature Reviews Endocrinology 6, 173-177 (2010)
The ability of human embryonic stem cells to differentiate into pancreatic islet cells has defined the developmental stages and transcription factors involved in this process. As a consequence, refinement of gene and stem cell therapies for patients with insulin-dependent diabetes mellitus has become an area of intense research. In this Perspectives article, Calne and colleagues comment on the progress of these experimental therapies, which might one day become a clinical reality.
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