Genes for Type 1 Diabetes in Decline

Type 1 and LADA
1

Studies of ancient skeletons show that the prevalence of the genes predisposing people to develop type 1 diabetes is now lower than it used to be long ago, probably because the higher death rate among type 1 patients reduced the extent of their genes in the population. This decline in the diabetic genes is occurring alongside a rise in the number of new cases of type 1 diabetes by around 2 to 3% a year. This increase despite the reduced genetic susceptibility to the disease points to a rise of environmental factors responsible for the condition.

Int J Immunogenet Epub 2010 Mar 14.

Changes in frequency of IDDM-associated HLA DQB, CTLA4 and INS alleles.

H. W. Witas, et al.:

Abstract

The incidence of type 1 diabetes is increasing worldwide. In Poland, the number of cases tripled during the last two decades. The aim of this study was to test the hypothesis that the increase may be at least partly explained by a shift in predisposing alleles’ frequencies - resulting from treating the otherwise lethal disease, generally better health care as well as selective pressure imposed by pathogens affecting humankind throughout history. The source of DNA was skeletal remains of 232 individuals excavated in four burial sites, dating back to 11th-14th centuries. With all necessary precautions required in ancient DNA analysis, frequencies of HLA DQB(57), CTLA4+49A/G and INS -23A/T alleles were assessed and compared with available data, characterising contemporary Polish population. Frequency of HLA DQB(57-Asp) protective allele is much higher in present-day population of Poland (50.6%) than in the group of 155 medieval specimens successfully typed for this polymorphism (28.4%, P < 0.001). Out of 86 medieval individuals typed for CTLA4+49A/G, 29.1% were homozygous for the predisposing G allele, which is significantly more than contemporarily - 7.6% (P < 0.001). No statistically significant difference was found in alleles and genotypes frequencies of INS-23A/T polymorphic site. Contrary to the initial assumptions, genetic predisposition towards type 1 diabetes, conferred by HLA DQB(57), CTLA4+49A/G and INS -23A/T alleles is much lower contemporarily than it was approximately 700 years before present. This suggests involvement of other than genetic factors in the fast growing incidence of the disease.

2 Likes
2

That’s interesting. I have had Type 1 for about 25 years. I didn’t have insurance back then and have never been tested for specific genes related to Type 1. I do know that before I started having issues I went through a lot of stress and had Chickenpox prior. I do have autoimmune issues on both sides of my family so I am guessing I probably do have some sort of genes that made me more prone to have Type 1.

3

Some people have blamed type 1 diabetics for having children, since this increases the prevalence of the genes predisposing people to develop the disease. This then creates the ironic situation of the very people who complain all the time about there being no cure for diabetes themselves making the disease worse. But while it is certainly true that the survival since 1922 of type 1 diabetics diagnosed before adulthood has certainly contributed to there being more genetic risk for diabetes in the population than there otherwise would have been, the discovery of this study is that overall over a long time period of several centuries there has been a decrease in the genes for diabetes, no doubt because, before the 1920s, type 1 diabetics developing the disease in youth would just die off and not breed.

Then how do we explain the present increase in the number of diabetics? Probably because the other required factor, some environmental trigger for the disease, is increasing. I did some research on the disease many years ago at the British Library, and there I found some British medical books from the early 19th century expressing panic over the rise of diabetes among children. I also researched the topic in Germany and found the same comments in medical texts beginning in the mid-19th century. This led me to suspect that since the process of industrialization was earlier in England than in Germany, perhaps it was some factor associated with industrialization which was causing the rise of what was probably type 1 diabetes. Interestingly, there was also a rise in type 1 diabetes in Poland in the 1970s, which has also been associated with industrialization.

4

That definitely seems like a possibility of the increase. I know that I have German / European descendants in my family. I asked my doctor a while back about passing the Type 1 on to children. She stated that Type 1 Diabetes is passed on from the fathers genes and not the mothers. That if I had any children the chance of them getting Type 1 was the same as the general population. I was recently diagnosed with Inflammatory Arthritis and my specialist found the HLA-B27 gene. The information they gave me on that says that it is common for Autoimmune Arthritis related to this gene to be passed down on the mothers side. I have Autoimmune on both sides of my family.

Also, I do wonder if possibly a lot of the increase might have to do with the overuse of antibiotics.

5

I also have ADHD. I recently read “Delivered from Distraction” by Drs Edward Hallowell and John Ratey. (They are the leading ADHD researchers in They wrote a whole chapter about the “4 As” adhd, asthma, aspergers & autism all being caused with greater frequency since the advent of the wide spread use of plastics in our society. I believe that environmental factors, plastics, fertilizers/insecticides, over use of soap, etc play into the increase in diabetes as well as those other chronic conditions.

I find the comments about diabetics causing diabetes to be disengenuous. The risk percentage only raises from 3% to 6%. But you can’t expect us to not want our own children. We give up so much already.

6

While males with type 1 diabetes pass on a higher risk of the child having the disease than do females, and this risk varies according to the age of onset of the disease in both the male and female, both males and females pass on a genetic risk for developing the condition. Here is the summary of one study on the topic:

"Clin Chem.Epub 2011 Jan 4.

Genetics of type 1 diabetes.

Steck AK, Rewers MJ

BACKGROUND:

Type 1 diabetes, a multifactorial disease with a strong genetic component, is caused by the autoimmune destruction of pancreatic β cells. The major susceptibility locus maps to the HLA class II genes at 6p21, although more than 40 non-HLA susceptibility gene markers have been confirmed.

CONTENT:

Although HLA class II alleles account for up to 30%-50% of genetic type 1 diabetes risk, multiple non-MHC loci contribute to disease risk with smaller effects. … Children born with the high-risk genotype HLADR3/4-DQ8 comprise almost 50% of children who develop antiislet autoimmunity by the age of 5 years. Genetic risk for type 1 diabetes can be further stratified by selection of children with susceptible genotypes at other diabetes genes, by selection of children with a multiple family history of diabetes, and/or by selection of relatives that are HLA identical to the proband.

SUMMARY:

Children with the HLA-risk genotypes DR3/4-DQ8 or DR4/DR4 who have a family history of type 1 diabetes have more than a 1 in 5 risk for developing islet autoantibodies during childhood, and children with the same HLA-risk genotype but no family history have approximately a 1 in 20 risk. Determining extreme genetic risk is a prerequisite for the implementation of primary prevention trials, which are now underway for relatives of individuals with type 1 diabetes."

The ethical question of whether you should have children when you know in advance that you will pass on to them an elevated risk of serious illness is one that we all face. No matter how small the risk is, deliberately deciding to impose that risk on your own future child, someone to whom you owe the highest moral duties of protection, seems inconsistent with a parent’s role. I remember when Michael Jackson dangled his young son over a Berlin hotel balcony in 1985 he was widely condemned, not for harming the child, but just for having unnecessarily exposed him to a risk.

On the other hand, you could argue that bringing anyone into the world imposes a risk on that person to which they cannot consent in advance, since the world can be a horrible place. Some Polynesian cultures weep when a new child is born because of their awareness of how terrible the world can be for those in it. But if no potential parent can eliminate all possible risks a child may face, where do we draw the line in determining when it is ethical to have children? Should the poor, for example, not have children because they cannot protect them as well as others can against the risks of life? What about passing on a risk of short stature, which has been shown to reduce employment chances for males? Is that too much of a negative risk for the parents to have children? It is all a matter of degree. The philosopher David Benatar has even recently written a book arguing that it is always a bad idea to have children because life is basically so terrible.

For myself, I decided I would have to slit my throat if I had a child who turned out to have type 1 diabetes, so I never had any. Others may draw the ethical line at a different point. Like all line-drawing problems, the right decision is unclear.
.

7

I think deciding to have a child or not is up to each person. Adopting a child is a great option too. I don’t know of any Type 1 Diabetics in my family but we do have other autoimmune diseases. I know that it’s easy to have a lot of mixed feelings about it especially if you have personally experienced dealing with Diabetes. I really didn’t think I could have a child when I was in my 20’s and my doctor told me he didn’t think I would make it to 30. I am now in my 40’s and have a child. It really makes me mad to this day that some people don’t realize the impact they have on others. I’m sure the doctor was trying to scare me into taking care of myself but all he did was make things worse.

The way I look at things now is that you really can’t control what will happen in life. I had a friend of mine die back in high school from something she caught a few days before. She was completely healthy until then. So I definitely feel blessed for having what I do in life especially knowing that I could have had the same thing happen to me.

1 Like
8

A very different explanation for a different observation, that T1 diabetes is far more prevalent in those from Northern Europe, is explored here : https://www.nytimes.com/2005/05/17/health/new-theory-places-origin-of-diabetes-in-an-age-of-icy-hardships.html

When temperatures plummet, most people bundle up in thick sweaters, stay cozy indoors and stoke up on comfort food. But a provocative new theory suggests that thousands of years ago, juvenile diabetes may have evolved as a way to stay warm.

People with the disease, also known as Type 1 diabetes, have excessive amounts of sugar, or glucose, in their blood.

The theory argues that juvenile diabetes may have developed in ancestral people who lived in Northern Europe about 12,000 years ago when temperatures fell by 10 degrees Fahrenheit in just a few decades and an ice age arrived virtually overnight.

Archaeological evidence suggests countless people froze to death, while others fled south. But Dr. Sharon Moalem, an expert in evolutionary medicine at the Mount Sinai School of Medicine in New York, believes that some people may have adapted to the extreme cold. High levels of blood glucose prevent cells and tissues from forming ice crystals, Dr. Moalem said. In other words, Type 1 diabetes would have prevented many of our ancestors from freezing to death.

9

I do find this post way out there. I mean if because I have diabetes, I should not have children because my children might carry a gene. From that standpoint, most people should not have children because they carry a gene that could cause something. I mean really, we would not be having children with this mindset. Please stop preaching death and doom. You always, always have such a negative outlook on everything.
Yes, life is not fair. And yes diabetes doesn’t play fair but wow, life is good. Go out and enjoy the sunset tonight and think about all the good you have.

10

By definition, things you do which impact others are ethical issues, and ethical issues, like deciding to murder someone, steal someone’s money, or push them down the stairs, are topics of public moral judgment, not up to each person. If it is unethical to have a child if you pass on to them the risk of diabetes, then it is a public moral issue, not up to each person. But the problem is, as I commented in the earlier post, that deciding how much risk you can ethically impose on a potential child is extremely difficult to determine. Imposing a known risk of spina bifida may be too much to be ethical, imposing a known risk of a club foot may not be small enough not to be a problem, but where does type 1 diabetes fall on the scale? Courts now give children born with serious genetic illness ‘wrongful birth’ awards against the doctors who failed correctly to prevent their being born with the problems they have, so the society seems to accept that even the gift of life, if burdened by illness, can be regarded as something that cannot ethically be given.

A problem with diabetics adopting children is that many adoption agencies refuse to place children with diabetics, viewing parents with the disease as not suitable. These agencies should appreciate that diabetics choosing adoption are trying to be ethical in not having biological children, but they take the view that if the child has lost its biological parents, it shouldn’t face an increased risk of losing its adoptive parents.

While we never know how things will turn out, all human planning is based on the awareness that we can anticipate what will follow from the choices we make, and that is why we are ethically responsible for those choices, even if we cannot be certain what will happen as a result of them. Thus if I punch someone and he dies unexpectedly because he is quite weak, I am guilty of manslaughter. I couldn’t know what would happen, but I did take the chance of something happening.

11

What you are discussing is quite close to the topic I posted earlier about the so-called ‘Viking Hypothesis,’ which is that the gene for diabetes once offered some protection against extreme cold and was of benefit in the last Ice Age, and that it was most developed in population groups that later formed the Vikings. That is why everywhere the Vikings settled, such as Sicily, for example, diabetes rates are high, just as they are where the Vikings originated, such as Denmark.

12

Honestly I have never attempted the adoption process so I really don’t know. But, I would hope that there are some that would be more focused on the actual potential parent being good for the child and not on their medical problems. I mean most people have some type of medical problem or personal issues they deal with each day. I really don’t know a lot of people who are completely healthy and never see the doctor. But even if someone wasn’t able to adopt there are other ways of helping kids or working with kids.

I know Diabetes can be a major pain in the butt and is a constant aggravation. Believe me I have had bad times and gone through depression and anxiety. But, all I know at this point is that life is to short to let it get to me anymore. I refuse to let something like Diabetes take over my life. So I keep trying to focus on all of the good things. There are too many good things in life. Sometimes it’s just hard to see that. No matter what your medical condition there are new advances in the medical industry each day. So I just don’t think it’s right to tell people they can’t have kids especially if a certain disease could be cured or a new medicine comes out during their lifetime.

I could never be mad at my parents even if they had Type 1 and passed it on to me. It isn’t their fault and I am glad to be alive. Yes it is a rough life but I try to think that things can always be worse. I have several autoimmune diseases and I would never be the person I was today without going through all I have in life.