Diabetes mellitus type 1 primary prevention

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Priyamvada Singh, M.B.B.S. [2]; Cafer Zorkun, M.D., Ph.D. [3]Vishal Devarkonda, M.B.B.S[4]

Overview

Currently there are no primary preventive measures available for type 1 DM. However, there are clinical trials ongoing that aim to find methods of preventing or slowing its development.

Primary Prevention

There is currently no preventive measure that can be taken against type 1 diabetes. Most people affected by type 1 diabetes are otherwise healthy and of a healthy weight when onset occurs, but they can lose weight quickly and dangerously, if not diagnosed in a relatively short amount of time. Diet and exercise cannot reverse or prevent type 1 diabetes. However, there are clinical trials ongoing that aim to find methods of preventing or slowing its development.

Immunization Approach

If a biochemical mechanism can be found that prevents the immune system from attacking beta cells, it may be administered to prevent commencement of diabetes type 1. The way several groups are trying to achieve this is by causing the activation state of the immune system to change from Th1 state (“attack” by killer T Cells) to Th2 state (development of new antibodies). This Th1-Th2 shift occurs via a change in the type of cytokine signaling molecules being released by regulatory T-cells. Instead of pro-inflammatory cytokines, the regulatory T-cells begin to release cytokines that inhibit inflammation.[5] This phenomenon is commonly known as "acquired immune tolerance".

DiaPep277

A substance designed to cause lymphocyte cells to cease attacking beta cells, DiaPep277 is a peptide fragment of a larger protein called HSP60. Given as a subcutaneous injection, its mechanism of action involves a Th1-Th2 shift. Clinical success has been demonstrated in prolonging the "honeymoon" period for people who already have type 1 diabetes [6]. The product is currently being tested in people with latent autoimmune diabetes of adults (LADA). Ownership of the drug has changed hands several times over the last decade. In 2007, Clal Biotechnology Industries (CBI) Ltd., an Israeli investment group in the field of life sciences, announced that Andromeda Biotech Ltd., a wholly owned subsidiary of CBI, signed a Term Sheet with Teva Pharmaceutical Industries Ltd. to develop and commercialize DiaPep277[7].

Intra-Nasal Insulin

There is pre-clinical evidence that a Th1-Th2 shift can be induced by administration of insulin directly onto the immune tissue in the nasal cavity. This observation has led to a clinical trial, called INIT II, which began in late 2006, based in Australia and New Zealand.

Denise Faustman Research

Tumor necrosis factor-alpha, or TNF-a, is part of the immune system. It helps the immune system discern between self and non-self. Type one diabetics are deficient in this substance. Dr. Faustman discovered that giving BCG, an inexpensive drug, to diabetic mice, stimulates TNF-a production. TNF-a kills the white blood cells responsible for destroying beta cells, and thus prevents, or reverses diabetes[1]. She has reversed diabetes in laboratory mice with this techniqe, but was only able to receive funding for subsequent research from Lee Iaccoca. Human trials began in 2007, and are still underway.

References

  1. Shinichiro Ryu, Shohta Kodama, Kazuko Ryu, David A. Schoenfeld & Denise L. Faustman. 2001. Reversal of established autoimmune diabetes by restoration of endogenous β cell function. J. Clin. Invest. 108(1): 63-72.

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