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Causes of Type 1: Genes

If only we knew the answer to the question ‘What causes Type 1 diabetes?’ Then we might be able to answer, ‘How can we cure  Type 1 diabetes?’

Of course, we can’t just yet, but a lot of people are working on it as I write. Tantalisingly there are reports from time to time of people reversing their Type 1 diabetes. That is great. But if it happens to anyone of us, and I hope it does, then be prepared to be whisked off to a lab somewhere and taken apart to find out what happened. You will become medically very valuable, indeed.

But at this moment in time, all we can do is try to piece together all of the threads and see what we come up with. I delivered a lecture on this topic recently. Being a GP and not a research specialist, it took ages to research. But it was fascinating. There are so many possible reasons, but we haven’t quite nailed it. The trouble is, when you find something you have to ask yourself, is what I have measured just an association? Is it something that has got tangled up with the process? Or has it caused the problem, or is it just caught up as a consequence of the cause? For example, If there is a civil disorder, you don’t want to worry exclusively about the masses who get caught up in the whole thing—no point in worrying about the looters nicking the tellies. It would be best if you had the ringleader who is plotting the downfall of society. But you do need to control the masses as well, just so that you can keep order. So there is every reason to tackle the problem from as many points as possible.

That’s a little dramatic, but you get the drift. And to date, in Type 1 diabetes to continue the metaphor, the actual ringleader seems to be still at large.

From what I have found, there are many suspects. Genetics. These are probably close to the top of the list. Inflammation; there are lots of so-called inflammatory markers being measured. But what is driving that inflammation? Viruses are always good to pick on. They are always around when there is trouble. The microbiome? That seems to be the answer to everything. Vitamin D? there does seem to be an association. But is it a cause?

Let’s take a look.


There are undoubtedly associations between genes and Type 1 diabetes. If you have specific genes, then you are more likely to have Type 1 diabetes.

The so-called Human Leucocyte Antigen system, HLA, is part of the immune system that helps immune tissues to recognise us as humans. There are proteins on the surface of white blood cells or leukocytes that regulate the immune system by helping the body to remove substances recognised as ‘foreign.’ The thinking goes that sometimes the body mistakenly identifies it’s own tissues as foreign and takes action to attack and destroy those tissues. The specific regions of the pancreas called islet cells are destroyed in Type 1 diabetes. They produce insulin, and when this happens, the person develops Type 1 diabetes as these cells are destroyed. Occasionally it occurs rapidly, but more typically, there is a gradual decline over months.

The HLA system is implicated in 40% of genetic risk for Type 1 diabetes. If you have HLA DQA1, DQB1, or DRB1 on chromosome 6, this means that you are more vulnerable to Type 1 diabetes. But it doesn’t mean that you definitely will get Type 1. There is a slightly increased risk if your father has Type 1 diabetes, 5% over your lifetime, so a 95% chance of not getting Type 1 this way, compared to your mother when you have a 2% risk.

If you want to avoid medical investigation, try not to be an identical twin. You are very useful because twins have identical genes. So if your twin brother or sister gets Type 1, what are your chances? It turns out that over seven years that you have a 27% chance of developing Type 1 diabetes. If you are a non-identical twin, then you have only a 3.8% chance over 23 years.

( Diabetes 52: 1052-1055,2003)

SNP or Snips.

The proper name for these is Single Nucleotide Polymorphisms. They are part of the genetic risk, but you don’t inherit these, you acquire them. What seems to happen is that when your body renews itself ( for example, the skin every few weeks, red blood cells every 2-3 months), your genetic tissue has to be copied precisely) Sometimes that copying process is not 100% accurate. Some of the copying processes insert the wrong building blocks. It sounds dire and can be if it affects those genes that are important. But a lot of the genetic tissue has no actual function that we know of (yet), so the inaccurate copying process might happen in these areas and cause no apparent harm.

Over a lifetime, any of us Type 1 or not, might have 4-5 million Snips in our genetic tissue (DNA). It makes us all unique. We can measure some of them and are aware of the function of a few thousand. There are thought to be 100 million snips in the whole population, so there is a way to go yet.

So what does this all mean for Type 1’s?

Well, so far, just eight snips have been linked with Type 1 diabetes. Interestingly 5 of them give you an increased risk of getting Type 1 and 3 seem to reduce your risk.

If you have had your DNA analysed, you can look them up in the data that you get with your results.

For example, PTPN22 will increase your risk of Type 1 diabetes, vitiligo, SLE and autoimmune thyroid disease called Graves Disease, but it will decrease your risk of inflammatory bowel disease such as Crohn’s Disease.

What can you do about it? Not a lot in reality. As we have said before, though, the increased risk does not mean that you will get Type 1 if you have PTPN2