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From Phoenix, Arizona, USA:

I have a 13 year old son that was diagnosed Type 1 two years ago. A year ago, my 17 year old tested positive for ICA and insulin antibodies and does not have the protective gene (HLA?). My 9 year old son just tested positive for ICA after testing negative one year ago. We are working with the Diabetes Prevention Trial for further testing.

My questions are:

  • How much do all of these genetic markers mean?
  • What are my nondiabetic sons' chances of becoming diabetic?
  • My sister and her daughter are also Type 1 diabetics. Is this cluster unusual?


The HLA and antibody markers that you asked about are all measures of the probability of developing insulin dependent Type 1 Diabetes, the kind that your 13 year old has. For just one antibody, these chances in preliminary studies are about 8% after 3 years, 15% at five years and about 20% at 10 years. The likelihood can be more precisely defined by measuring what is called first phase insulin release (i.e., serum insulin levels after a glucose load). With two antibodies, the respective figures are 30%, 40% and 70%. With all three antibodies present there is a 100% chance of clinical diabetes in 5 years.

Three studies are in progress at the moment. In Europe, there is a trial of nicotinamide to see if it will defer insulin dependence. In this country, for those with two or more antibodies,there is a trial of small doses of injected insulin and in the last month a third trial of 'vaccination' with oral insulin has begun. Another contemporary trial called DAISY is attempting to evaluate the environmental factors that trigger the conversion of genetic susceptibility to a damaging auto-immune process.

The objective of HLA typing is to establish risk tables for the various patterns (haplotypes). From these it will be possible to devise tests that have a maximum chance of detecting future diabetics before antibodies develop and at reasonable cost.

Plans are already underway for screening population samples thus selected, perhaps in the newborn, perhaps prekindergarten, with a view to actually preventing clinical diabetes rather than just deferring insulin dependence. Again, oral insulin may be used for 'vaccination' and perhaps also a fragment of the B chain of insulin (B9-23) that has shown promise in the NOD mouse when injected.

The high incidence of Type 1 diabetes in your family may be just statistical misfortune or it may be due to a unique HLA gene. In Norway, for example, the HLA type DRB1*0401 was reported to confer a fivefold increase risk of clinical diabetes.

A complex story; I hope this gives you a glimpse.


Original posting 20 Nov 96


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Last Updated: Tuesday April 06, 2010 15:08:52
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