MODY

These initials stand for Mature Onset Diabetes of the Young.(Also Known as Monogenic Diabetes.) It affects one to two per cent of people with diabetes and is often unrecognised.

The normal early signs of diabetes, like thirst and frequent urination, creep up very slowly and the first the patient may know of it is when high fasting blood glucose levels are picked up at a general medical check-up, and how many of us actually get these done?

To distinguish MODY from type 1 diabetes tests need to be done to establish the absence of diabetes antibodies (anti-insulin, anti-islet, anti-GAD).

In obese people the absence of Insulin Resistance, (which will be shown by a c-peptide test), will differentiate it from type 2 diabetes.

It is the one form of diabetes that is a definite genetic disorder. MODY is caused by changes to a single gene and if either one of the parents carries this gene they have a 50% chance of passing it on to their child. For the technically minded this is known as autosomal dominant inheritance. So MODY can appear in several generations of a family.

People with MODY in the family line who are worried about this may wish to prevail themselves of genetic counselling.

How may a diagnosis of MODY be made?

In a non-obese patient of any age or in an obese patient less than 50 year of age....

1. You would present with higher than normal blood glucose.
2. You would have no ketones in your urine.The test for diabetic antibodies would be negative.
3. A Monogenic Diabetes (MODY) Evaluation test would be done.
4. If this is positive you have MODY. (if negative you are then a type 2 diabetic).

Why you may ask, if I have MODY, does it matter what the name of the gene is that is causing it?

Yes, it is important, because the type of MODY caused by the different genes differs.

If you know what type of MODY you have you can treat it correctly. Also it enables your health advisers to advise you on how the disease is going to progress. Lastly it enables you to let other family members know what they may have inherited, so their doctors can better target their tests.

MODY types 1, 3, 4, 5, and 6 control the way insulin is produces from the beta cells. They are termed 'transcription factors'.

The genes have mutated in such a way that they prevent the efficient stimulation of the beta cells to produce insulin. In all, except type 6, some mechanism, which we do not yet understand, will eventually end in the total failure of the beta cells to produce insulin.

In MODY type 2 the mutated gene is for the enzyme glucokinase. This is the body's "glucose sensor". When it does not work properly higher amounts of glucose are needed before the beta cells get the message to release insulin.

The classifications of MODY are as follows:-

Type 1

Affected gene - HNF4alpha
Affected protein - Hepatocyte nuclear factor 4 alpha
Prevalence - Uncommon

Type 2

Affected gene - GCK
Affected protein - Glucokinase
Prevalence - Common

Type 3

Affected gene - TCF1
Affected protein - Hepatic nuclear factor 1 alpha (HNF1alpha)
Prevalence - Most common

Type 4

Affected gene - IPF1
Affected protein - Insulin promotor factor 1
Prevalence - Uncommon

Type 5

Affected gene - TCF2
Affected protein - Hepatic nuclear factor 1 beta (HNF1 beta)
Prevalence - Uncommon

Type 6

Affected gene - Neuro D1
Affected protein - Neurogenic differentiation factor 1
Prevalence - Very rare

Though all forms of MODY are associated with some level of blood glucose rise there are also other factors involved. For instance:-

MODY Type 1

Defects in the HNF-4a gene also affect fatty acid synthesis in the liver.

MODY Type 2

This type of MODY is very mild and often symptomless. It is it's mild glucose intolerance that serves to separate it from other forms of MODY. It is often picked up on routine testing, either in a pregnant woman who may suspect a family history, in obese patients or the elderly. Fortunately it rarely causes any complications.

MODY Type 3

This is a progressive type - in other words you may produce sufficient insulin as a child but as you get older the amount decreases. It is usually diagnosed sometime after puberty.

You need to control your blood glucose well with this type as you are susceptible to diabetic complications such as retinopathy (eye problems) and nephropathy (kidney damage).

The gene defect causes a decrease in the kidneys re-absorption of glucose which results in glucose being secreted in the urine (Glycosuria).

MODY Type 4

This type produces a relatively mild form of diabetes. It is rare, (having only been found in one family to date in the UK) so not much is known about it.

MODY Type 5

A problem one this, as defects in the HNF-1 protein have also been known to cause renal cysts and other abnormalities in kidney development. That is why it is often only diagnosed after the diagnosis for kidney disease.

Unfortunately a diagnosis based just on the presence of kidney disease is not enough to indicate MODY 5 as it may also be a sign of diabetic nephropathy in Type 1 & 2 diabetics. MODY 5 is also known to cause internal genital abnormalities and atrophy of the pancreas.
Fortunately it is very rare.

MODY Type 6

Only found in 2 families in the UK to date.

For more information about MODY tests try the following link -

Athena Diagnostics


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