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March 4, 2001

Genetics and Heredity

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Question from Maple Valley, Washington, USA:

My four year old son is in the pre-clinical stage of type�1A (autoimmune) diabetes. He is currently positive for islet cell antibodies, and he occasionally has blood sugars over 200 mg/dl [11.1 mmol/L], one hour after eating. He is also having a lot of trouble with hypoglycemia, especially upon waking or after having had more exercise than usual (40s and 50s mg/dl [2.2 to 2.8 mmol/L]). Because of this, he is not able to take the small amounts of insulin suggested by doctors in the DPT-1 study so he is currently using nicotinamide. He is being monitored by a wonderful pediatric endocrinologist in Seattle. However, your site has been a real help to me in learning all I can about every aspect of type 1.

I see parents writing in asking about the likelihood of having another member of their immediate family (a child or sibling) develop diabetes, and I have seen your response that there is only a 2%-5% chance. Where are you getting your figures? My son will be the fourth generation of people with type 1 diabetes in my family. When I was growing up, we were told that there was a 20%-25% chance that either my sister or I would get diabetes (our dad has diabetes), and my sister developed it at age 10. Our father’s brother also has type 1, (another sibling situation), and also my father’s uncle had type 1. We have good friends who have two daughters with type 1.

I see so many situations in which type 1 is passed on that your numbers of 2%-5% shock me! Is this new information based on background information from the DPT-1 study? I certainly don’t know of any studies compiling all of our family histories. I just would like to know why the percentage has changed from a 20%-25% likelihood in the 1960’s (Virginia Mason research) to a 2%-5% stated now. Is this based on actual research compiled from all families with type 1 diabetes? If so, lightning strikes must be very prevalent in my family!

Answer:

From: DTeam Staff

This is now rather a complicated theme. Simply put though, the 2 to 5% figure has been derived from large population studies in primarily Caucasian families mostly in the US, Canada, Britain and the Scandinavian countries, especially Finland. These figures are inevitably approximate, first of all because no one has yet been able to identify the main environmental factors that trigger clinical diabetes in the genetically susceptible, and, secondly, because these figures were not corrected for the other, admittedly less common, forms of acute diabetes (type�1B). With so many unknown variables, there are inevitably both individual countries and small local pockets where the incidence is both higher and lower.

In recent years, the genetic contribution from the HLA antigen region on chromosome 6 has been classified according to whether it confers a high, medium or low risk of type�1A (autoimmune) diabetes. Another national study, DAISY, is trying to pinpoint the environmental triggers. The long term hope is that it might eventually be possible to screen all children for the likelihood of developing this form of diabetes and to prevent insulin dependence in the susceptible by vaccination or other means.

DOB
Additional comments from Dr. Stuart Brink:

The numbers of 2-5% are very consistent from around the United States, Canada and northern Europe over the past 15-20 years. The older studies were significantly biased in favor of what we call multiplex families in which several family members had diabetes and so the percentage estimates were significantly higher than we know to be the case. The numbers in the DPT-1 have confirmed these estimates.

All of us have seen families like you describe with many family members. They may have stronger genetic predisposition and often have thyroid disease as well as type 1 diabetes clustering together, some with other autoimmune endocrine disorders as well.

SB
Additional comments from David Mendosa, A Writer on the Web:
You might read the article What is Type 1 Diabetes? and its citations at the Genetic Health site. That article states

Although most people in the population have a 0.4 percent chance of developing Type 1 diabetes, the risk increases to about two percent if your mother has diabetes and six percent if your
father or siblings have Type 1 diabetes. If your sibling with diabetes is a fraternal twin your risk increases to 11 percent and it increases to roughly 50 percent if your identical twin has diabetes.

It is those twin studies that are probably confusing.

DM