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Can we predict and/or prevent type I diabetes?
Abstract
The highest risk for the development of type I diabetes resides with first-degree relatives of the diabetic proband, this risk being in the order of 2,9%, 6,6% and 4,9% for parents, siblings and children of the proband, respectively. The major genetic markers associated with the development of insulin-dependent diabetes mellitus (IDDM) is the possession of the HLA alleles OR3/DR4 and more recently the absence of aspartate in the 57th position on the β-chain of the HLA DO gene (HLA DO β Asp 57 negative). The most important auto-immune marker for predicting preclinical lOOM is the presence of high titres (> 40 Juvenile Diabetes Foundation units) of islet cell antibodies (ICA), while the finding of insulin auto-antibodies (IAA) is a good predictive marker in children < 5 years of age. The presence in a susceptible individual of ICA plus IAA is a better predictor of impending IDDM than the presence of either of these two markers alone. Antibodies which precipitate an islet membrane protein (MW 641<) are highly sensitive and specific markers of preclinical IDDM. The presence of 64K antibodies may well be the most important predictive marker of impending IDDM in the future. The progressive decline of the first phase of insulin secretion in response to an intravenous glucose challenge is associated with the onset of lOOM within 18 months. Of the immunotherapeutic agents at present used in clinically manifest IDDM, azathioprine has been shown to be ineffective in increasing the remission phase, while the value of nicotinamide is controversial. At present the agents showing the most promise in inducing and maintaining remissions are cyclosporin A or a combination. of prednisone plus azathioprine; however, further studies are needed. As regards the prophylaxis of IDDM, the use of immunotherapy in minute doses during the preclinical phase or the administration of a vaccine (derived from attenuated autoreactive T cells) to all newborn infants comprise some of the strategies envisaged for use in the future.
