What Causes Type 1 Diabetes?

[Marat]

Type 1 Diabetes is known to be caused by a genetic predisposition to autoimmune destruction of the beta cells of the pancreas, triggered by the patient's encounter with some unknown environmental factors. The genetic predisposition is not a very strong factor, however, since while the background risk of type 1 diabetes in the general population is 0.3%, for the children of type 1 diabetic fathers it is 7% and for the children of type 1 diabetic mothers it is 4%. Monozygotic type 1 diabetic twins are only 50% concordant for the disease, which seems quite strange, since they are usually raised together and are thus not only genetically identical but are also exposed to almost the same environmental influences, especially during their childhood. Since type 1 diabetes usually manifests at puberty, after many years of covert development during which the surviving beta cells compensate for the ones being destroyed by autoimmune processes, the exposure of these twins to different environmental triggers must occur quite early in life, when the cultural practice of rearing twins in nearly identical ways (food, clothing, handling, viral exposure) is common.

 

So what subtle environmental difference can possibly account for the disconcordance of type 1 diabetes in identical twins? The effects of different positioning in utero of genetically identical twins are one possibility which has been increasingly explored for other differences in identical twins lately, but I can't imagine the mechanism in such a case for explaining why one gets diabetes and the other doesn't. Children who are not breast fed and who instead drink cow's milk have a greater disposition to diabetes, and a diet of smoked meats in the mother at a certain stage of gestation have been cited as possible environmental triggers for type 1 diabetes, but these factors would not differ in identical twins.

[lemur]

I think identical twins tend to actively differentiate from each other in various ways in reaction to the social perception that they are indistinguishable. So it may be that factors that prevent or encourage diabetes in one twin are actively resisted in the other. That's what I would guess anyway.

[Sorcerer]

Seems like u've got the answer there, we don't know yet, maybe it could be a thesis for u. If I was gonna guess, I'd say diet and exposure to immune antagonists. Maybe its got something to do with the hygeine hypothesis http://en.wikipedia.org/wiki/Hygiene_hypothesis

 

a quick search of hygeine hypothesis and diabetes gave me this http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1120487/

[Marat]

The hygiene hypothesis is a good lead, and I often noted while reading medical texts from the early 19th century that a number of doctors then were in a panic about why the number of children with diabetes was suddenly increasing. Perhaps this was because there was less exposure to environmental challenges to the developing immune system of children as the world became more industrialized. I noted this panic over the rise of childhood diabetes only in English medical texts, not in American, French, or German, so since England was the only strongly industrializing country at that time, perhaps that is a clue.

 

But then we have the problem again in identical twins that the twins would almost always be reared together, so their environments would have been essentially the same, so where does the 50% disconcordance come from? Could exposure to viral triggers be so specific as to select one member of a twin pair in the same household but not the other? True, not everyone in the same house will always get the same virus, but these people do not live in the same environments the way very young twins do, and type 1 diabetes of adolescent onset starts developing many years before it manifests, so we are probably talking about five-year-olds somehow having different diets, exposure to different materials, and different exposure to viral triggers.

[SMF]

On reading this I was interested in finding out what the difference in concordance is for monozygotic twins when reared together and reared apart. This difference would give more information than just MZ verses DZ twins. There is a huge Finnish study with more than 20K twins that has a good representation of twins reared apart, but I couldn't find anything not behind a paywall. There were a lot of references to studies involved in epigenetics, so maybe this is another avenue to look into. SM

[venkyreddy]

Type 1 Diabetes is known to be caused by a genetic predisposition to autoimmune destruction of the beta cells of the pancreas, triggered by the patient's encounter with some unknown environmental factors. The genetic predisposition is not a very strong factor, however, since while the background risk of type 1 diabetes in the general population is 0.3%, for the children of type 1 diabetic fathers it is 7% and for the children of type 1 diabetic mothers it is 4%. Monozygotic type 1 diabetic twins are only 50% concordant for the disease, which seems quite strange, since they are usually raised together and are thus not only genetically identical but are also exposed to almost the same environmental influences, especially during their childhood. Since type 1 diabetes usually manifests at puberty, after many years of covert development during which the surviving beta cells compensate for the ones being destroyed by autoimmune processes, the exposure of these twins to different environmental triggers must occur quite early in life, when the cultural practice of rearing twins in nearly identical ways (food, clothing, handling, viral exposure) is common.

 

So what subtle environmental difference can possibly account for the disconcordance of type 1 diabetes in identical twins? The effects of different positioning in utero of genetically identical twins are one possibility which has been increasingly explored for other differences in identical twins lately, but I can't imagine the mechanism in such a case for explaining why one gets diabetes and the other doesn't. Children who are not breast fed and who instead drink cow's milk have a greater disposition to diabetes, and a diet of smoked meats in the mother at a certain stage of gestation have been cited as possible environmental triggers for type 1 diabetes, but these factors would not differ in identical twins.

 

certain viral infections during childhood may trigger certain lymphocytes n induce antibodies against beta cells of pancreas which produces insulin

so in identical twins start of type 1 DM occurs if they r infected with certain viruses .....

its mainly depend on environmental ....identical twins have same genetic setup but external environmental stimulus creates differences in them..............

 

 

 

[pantheory]

So what subtle environmental difference can possibly account for the disconcordance of type 1 diabetes in identical twins?

There have been discovered epigenetic differences between some identical twins genetically, concerning animals. Concerning identical twins, I would suspect epigenetics as being suspect concerning genetic expression deficiencies such as possibly type 1 diabetes. The causes of epigenetic differences between identical twins probably can occur during conception or soon thereafter, but such causes of differences are now only speculative at best.

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Edited November 21, 2011 by pantheory