MIDD or Maternally
Inherited Diabetes And
Deafness.

This is a very rare form of Type 2 diabetes, accounting for only 1% of diabetics.

As is obvious from the name this type of diabetes is inherited only through the mother - termed maternal inheritance.

If you want to see how this works in picture form go to Genetics Home Reference.

So we Moms are to blame as usual are we - so what's different?

Actually in this case it is our eggs that are different. You see, eggs (ova) contain mitochondria, but sperm do not (we always knew Eve was a step up on Adam didn't we ladies?).

Cells cannot make new mitochondria. All the mitochondria in cells of the body are made by the replication of the original mitochondria in the mother's egg.

So, because all mitochondria comes from the mother and it is a defect in the genetic coding of the mitochondria that is responsible for MIDD, we have to claim responsibility for passing the chance of getting this disease on to our children. A father, though he may have the disease, cannot pass it on to his children.

Lets get a quick crash course on mitochondria......

Mitochondria are small organelles found within the cytoplasm of the cell.

They are responsible for generating ATP, which is the energy source needed by the cell to correctly perform it's metabolic functions.

Although most DNA is found in the nucleus of the cell the function of mitochondria is so important that they have been given their own DNA, known as mitochondrial DNA (mtDNA). This contains the genes needed for critical cell functions.

MIDD is caused by the mutation of a single gene, the MTTL1 gene, on the mtDNA. And in case you are wondering how that causes diabetes let me tell you that you are in good company - researchers know that the gene mutation is responsible, they just aren't sure why!

They do know that ATP plays a critical role in the production and release of insulin and, as stated, the mitochondria are responsible for generating ATP.

In MIDD it would appear that lower amounts of ATP are responsible for the change in the function of beta-cells in the pancreas.

A bit of interesting info for the scientifically minded -

The mutated gene is called A3242G.
The A stands for Adenine, a nucleotide of DNA
The G stands for Guanine, another nucleotide of DNA
It is the transposition of these two nucleotides that cause the mutation.
3243 is the position on the gene where the mutation occurs - the 3243rd position.
The way the scientific community have chosen to do their nomenclature the first letter stands for the correct nucleotide, then you get the position and lastly the incorrect nucleotide, thus A (correct), 3243 (position) and G (incorrect).

To distinguish this from normal Type 1 or 2 diabetes you have to look at both what is present and what is not.

What is present..........

1. In most cases MIDD develops around the ages of 25 - 35 years though it can come on later. Often the early onset MIDD is misdiagnosed as Type 1 while the late onset is likewise termed Type 2.
2. Generally these people are not obese. In fact they tend to have a low BMI.
3. Many have impaired hearing and cannot hear high-frequencies tones. This seldom develops into total deafness.
4. There is a high incidence of kidney disease amongst MIDD patients.
5. The tendency to become dependant on insulin occurs faster and at an earlier age than it does with other Type 2 diabetics.
6. Macular pattern dystrophy is very common in MIDD patients.
7. Both cardiomyopathy and neurological symptoms are present in MIDD, at a higher frequency than in the general population.
8. Insulin secretion is reduced.
9. Physical exercise causes an increase in lactate production.

What is not present............

1. No beta cell destruction despite reduced insulin secretion.
2. No islet antibodies, in fact no autoantibodies at all.
3. No insulin resistance.
4. No visceral obesity.

Why is MIDD so variable?

Why does it occur over such a range of ages and range so in severity. The answer has to do with the way we inherit the mitochondria.

Some of the mitochondria in the original ova may have had mutated genes and other may not.

When the cells divide the mitochondria are randomly distributed, so some cells will have more of the mutated genes than others.

The presence of what appears to be two different sort of genes is called heteroplasmy and the ratio of one type of gene to the other will determine the age at which MIDD develops.

For instance if a person gets pancreatic cells with more normal and less mutated genes they will develop diabetes later than the person with large numbers of mutated genes and few normal ones.

Likewise this will also affect the severity of the disease.

As we get older the cells which divide most frequently, like the skin or the blood, show decreased levels of heteroplasmy, while those that are more stable, like the cells of the muscles, nerves, brain and, need one add, the ears and pancreas, show an increase. That is probably why the disease sometimes appears later in life and appears to progress with age.

Treatment.

There is, as of this time, no cure for MIDD. With all the work going on with respect to genetic engineering we can hope that at some time in the future they will be able to manipulate the gene and correct it.

However that is indeed far in the future and we need to do the best we can now.

And the best is being able to slow down the symptoms or, if one is very fortunate, reverse them.

The first step to try is, as always, a healthy diet like in any Type 2 situation.

However there should not be a decrease in one's calorie count as MIDD patients are not overweight.

Note that I did not add increased physical exercise as it is contraindicated in MIDD, due to the tendency to produce excess lactic acid and also because patients suffer from muscle pain and weakness.

The normal first stage medication for Type 2 diabetics, Metformin, is also not recommended for MIDD patients. That is because it has been known to induce lactic-acidosis and people with impaired mitochondrial function are already in danger of having increased lactic acid production.

So the drug of choice is one of the Sulphonylureas, so long as the beta-cells are still secreting insulin. Once this slows right down it will be necessary to go onto insulin therapy.

It has been suggested that the use of CoQ10, alpha-lipoic acid and thiamine may have some benefits but this has not been proven. Like most diabetic decisions - it is up to you.

Genetic Testing.

Although a genetic test for this disease does exist it is really only used for research purposes.

As such a tiny part of the overall population is affected by MIDD I doubt it would be considered financially viable to make this commercially available, especially as a general screening device.

Even if you knew you had the gene there is nothing anyone could do in terms of curing it or changing the way it would be treated.

 


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