MODY affects 1-2% of people with diabetes but often goes unrecognised. It is a dominantly inherited genetic condition, therefore children of an affected parent with MODY have a 50% chance of inheriting the gene and developing MODY themselves.
Despite being called maturity onset diabetes of the young, it is not Type 2 diabetes in a young person. People with MODY do not produce enough insulin, compared to Type 2 diabetes who are resistant to the insulin they make.
The four main features are:
- Diabetes often develops before the age of 25.
- Diabetes runs in families from one generation to the next.
- Diabetes may be treated by diet or tablets, and does not always need insulin, or sometimes only a very low dose.
- Patients often of normal weight.
There are different types of MODY which progress in different ways and respond differently to certain medications. Therefore it is important to recognise MODY and its subtypes so that the most appropriate treatment can be determined. It will also allow us to advise people more accurately about how their diabetes will progress.
Family members of a patient known to have MODY should be aware of the symptoms of diabetes, and have their blood glucose measured if concerned.
The different types of MODY
There are different types of MODY (6 genes discovered so far).
The main types are:
MODY 3 – Hepatic Nuclear Factor 1 Alpha (HNF-1 alpha)
Changes in the HNF-1 alpha gene account for 70% of cases of MODY. It causes diabetes by lowering the amount of insulin produced by the pancreas. The diabetes usually develops in adolescence or early twenties, but sometimes later. There is often a very strong family history of diabetes. MODY 3 may be misdiagnosed as Type 1 diabetes, but these patients will be autoantibody negative at diagnosis.
Patients with MODY 3 are extremely sensitive to sulphonylureas. To avoid profound hypos the dosage of sulphonylureas needs to be greatly reduced compared to that used for those with Type 2 diabetes.
It is worth being aware that those with MODY 3 tend to have glycosuria at quite normal blood sugar levels and can develop kidney disease before a diagnosis of diabetes is finally made.
MODY 2 – Glucokinase
The glucokinase gene regulates the amount of insulin produced by the pancreas in response to blood glucose. Changes in the glucokinase gene means the blood glucose level is ‘reset’ at a higher level, typically between 6-8mmol/l. It is rare for MODY 2 to need treatment other than diet. There tends to be little change in blood glucose levels over the years unlike other types of diabetes, and as a result it is rare to develop diabetic complications. The only exception to this is in pregnancy, when the mother may need insulin to keep the blood glucose controlled.
MODY 1 – Hepatic Nuclear Factor 4 Alpha (HNF-4 alpha)
This presents similarly to HNF-1 alpha but is much less common.
MODY 5 – Hepatic Nuclear Factor 1 beta (HNF 1 beta)
This type of MODY is very rare, but it is important to recognise because of the strong association with kidney problems in the form of renal cysts.
Indications for referral and genetic testing
Testing is only necessary where it is going to change clinical management and is done via the Monogenic Diabetes Clinic.
Children and Adolescents with Mild Hyperglycaemia; Glucokinase Gene Mutations (MODY 2)
A fasting blood glucose in the range 5.5-8mmols/l is unusual in children and young adults and raises the concern that they may be about to develop Type I Diabetes. However a large proportion of these patients will have an alteration in the glucokinase gene and will never need treatment other than diet and will not develop diabetic complications. In these cases the fasting hyperglycaemia is persistent and stable over months or years. A parent may have the diagnosis of mild type 2 diabetes.
Gestational Diabetes: Glucokinase Gene Mutations (MODY 2)
Glucokinase patients have mild fasting hyperglycaemia throughout life bit this may only be picked up in pregnancy when routine tests are performed. If the woman has persistently raised fasting blood glucose before, during and after pregnancy then glucokinase testing may be appropriate. This has implications for her future care as her diabetes will not deteriorate with time or be associated with complications. The baby may also inherit the same mutation and present with a raised blood glucose.
The age of onset of MODY 2 depends on which parent passed on the mutation. It is at a significantly younger age if it was the mother who passed on the gene and if she had gestational diabetes. So if a young person is diagnosed with diabetes in their 20’s, is not overweight and mother had gestational diabetes-MODY 2 is definitely a possibility.
Children and Adolescents With Diabetes and a Strong Family History: HNF1-alpha (MODY 3) and HNF4-alpha (MODY 1) Gene Mutations
Testing may be appropriate in this case as it establishes that the patient is likely to remain non insulin dependant throughout life (although a third will ultimately need insulin but at lower doses). These patients are also very sensitive to sulphonlyureas and so long as they do not have problems with hypoglycaemia can be maintained on these for many yrs. Genetic counselling of the risk to offspring can also be offered.
Contacts
Patients can be discussed with:
Professor Mark Walker
Monogenic Diabetes Clinic
Newcastle Diabetes Centre
Campus for Ageing and Vitality (former Newcastle General Hospital site)
Westgate Road
Newcastle upon Tyne
Telephone: 0191 2823844
