Prevention of type 1 diabetes mellitus
- David K McCulloch, MD
David K McCulloch, MD
- Clinical Professor of Medicine
- University of Washington
- Massimo Pietropaolo, MD
Massimo Pietropaolo, MD
- McNair Type 1 Diabetes Scholar
- Professor of Medicine, Pathology and Immunology
- Baylor College of Medicine
- Section Editors
- Irl B Hirsch, MD
Irl B Hirsch, MD
- Section Editor — Diabetes Mellitus
- Professor of Medicine
- University of Washington School of Medicine
- Joseph I Wolfsdorf, MB, BCh
Joseph I Wolfsdorf, MB, BCh
- Section Editor — Pediatric Endocrinology
- Professor of Pediatrics
- Harvard Medical School
The increase in understanding of the pathogenesis of type 1 diabetes mellitus (formerly known as insulin-dependent diabetes mellitus) has made it possible to consider intervention to slow the autoimmune disease process in an attempt to delay or even prevent the onset of hyperglycemia. This topic will review current and planned efforts to prevent type 1 diabetes. Subjects who are at high risk for type 1 diabetes can be identified using a combination of immune, genetic, and metabolic markers. (See "Prediction of type 1 diabetes mellitus".)
In the current classification of diabetes, immune mediated type 1 diabetes is called type 1A to distinguish it from less common cases in which an autoimmune etiology cannot be determined (type 1B); the latter are said to be idiopathic . The term type 1 diabetes used here refers to type 1A, or autoimmune diabetes. (See "Classification of diabetes mellitus and genetic diabetic syndromes".)
PREVENTION AND REVERSAL STRATEGIES
Several immunosuppressive and immunomodulatory agents and other drugs have been given either alone or in combination to decrease the immune-mediated destruction of beta-cells that occurs in type 1 diabetes . Most of the studies have been performed in recent onset diabetes where the majority of beta-cell function has already been lost, and the anticipated outcome is preservation of remaining beta-cell function, usually measured as area under the curve (AUC) insulin secretion in response to stimulation. Many of the studies involve small numbers of patients and are uncontrolled.
Azathioprine — Azathioprine is an immunosuppressive drug that inhibits or prevents T cell responses to antigen. In one randomized, double-blind study of 46 patients treated with azathioprine and glucocorticoids, insulin could be discontinued in 10 of 20 treated patients, as compared with 2 of 20 patients in the placebo group . Endogenous insulin secretion (measured as the plasma C-peptide response to a liquid meal) also improved. However, only three treated patients remained in remission at one year. Equally discouraging results were noted in a second study .
Mycophenolate mofetil — Mycophenolate mofetil (MMF, Cellcept) inhibits proliferation of both T- and B-lymphocytes. In a multicenter randomized trial, 126 patients with type 1 diabetes for less than three months were randomly assigned to MMF, MMF plus daclizumab (an anti-IL-2 receptor monoclonal antibody that selectively binds the IL-2 receptor, inhibiting IL-2 mediated T-lymphocyte proliferation) or placebo . After two years, there was no significant difference in the mean AUC for C-peptide levels during a mixed-meal tolerance test. Thus, neither MMF alone or in combination with daclizumab slowed progression of beta-cell destruction in recently diagnosed type 1 diabetes.
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- PREVENTION AND REVERSAL STRATEGIES
- - Azathioprine
- - Mycophenolate mofetil
- - Cyclosporine
- - Anti-CD3 antibodies
- - Rituximab
- - Interleukin-1 inhibition
- - Thymoglobulin
- - Insulin
- - Immunotherapy DAB486-IL-2
- - GAD65 immunotherapy
- - Costimulation modulation
- - Bacillus Calmette-Guerin (BCG)
- - DiaPep277
- - Donor splenocytes
- - TNF-alpha inhibitors
- - Interferon alpha
- - Nicotinamide
- - Vitamin D supplements
- - Omega-3 polyunsaturated fatty acids
- - Avoidance of cow's milk
- - Hematopoietic stem cell transplant
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS