MODY diabetes (maturity onset diabetes of the young): causes, types and testing

Diabetes UK describes MODY as a rare form of diabetes which is different from both type 1 and type 2 diabetes, and which runs strongly in families. It is caused by a change in a single gene, which is why it is sometimes called monogenic diabetes. The diabetes, in general terms, develops because of a problem with how the pancreas makes or releases insulin, which is the hormone that helps the body use glucose for energy, as the NHS explains in its general guide to diabetes.

The key features, in Diabetes UK’s words, are being diagnosed with diabetes under the age of 25, having a parent with diabetes with diabetes in two or more generations, and not necessarily needing insulin. The Exeter genetics team gives the same three main features: diabetes often develops before the age of 25, it runs in families, and it may be treated by diet or tablets and does not always need insulin.

MODY is very rare compared with type 1 and type 2 diabetes. Diabetes UK says experts estimate that only 1 to 2% of people with diabetes, around 20,000 to 40,000 people in the UK, have it. The Exeter team likewise says MODY affects 1 to 2% of people with diabetes, although it often goes unrecognised.

Because MODY is so rare, doctors may not be aware of it. Diabetes UK says it is estimated that about 90% of people with it are mistakenly diagnosed with type 1 or type 2 diabetes at first. That matters because the right treatment depends on the type: some people diagnosed with type 1 diabetes, for example, may be able to stop insulin once the correct MODY type is identified, as Diabetes UK indicates when it lists stopping insulin as one reason to know.

MODY follows an autosomal dominant pattern. The Exeter team explains that a change in a single gene is passed on by affected parents to their children, and all children of an affected parent have a 50% chance of inheriting the affected gene and developing MODY themselves. Diabetes UK says that a child who inherits the mutation will generally develop MODY before the age of 25, whatever their weight, lifestyle or ethnic group.

Knowing the diagnosis therefore has implications for relatives. Diabetes UK notes that you can consider and discuss the risk to any children you have or plan to have, and that genetic testing can be offered to other family members.

Different genes lead to different types of MODY, which behave differently and need different treatment. The Exeter team says that changes in the genes HNF1A, HNF4A, GCK, HNF1B, KCNJ11 and ABCC8 account for 87% of UK MODY, with 13% not yet accounted for. Diabetes UK describes the most common types as follows.

Diabetes UK suggests that if you think you might have MODY you should discuss testing with your doctor. Testing involves having blood taken for pancreatic antibodies and blood or urine tested for C-peptide, and having blood taken for genetic testing. Your doctor or hospital takes the blood and sends it to the specialist centre in Exeter, along with details of your diagnosis and treatment.

The Exeter genetics teams have developed a MODY probability calculator to help healthcare professionals estimate the probability of someone having MODY. Diabetes UK stresses that it is not a tool to diagnose diabetes, so you will need to speak to your GP or healthcare team if you have questions. The Exeter laboratory offers testing by next generation sequencing of all known MODY genes, as well as single-gene tests for GCK and HNF1B.

Treatment depends on the type, which is why the genetic diagnosis matters. As the table above shows, HNF1-alpha and HNF4-alpha MODY are typically treated with sulphonylurea tablets, HNF1-beta usually needs insulin, and glucokinase MODY needs no treatment.

Diabetes UK says all types of MODY apart from glucokinase carry a risk of the long-term complications of diabetes, so a healthy balanced diet and regular physical activity matter because they help maintain good blood glucose and cholesterol levels, which in turn reduces the risk of complications. The NHS lists complications of diabetes generally as heart attack and stroke, kidney problems, nerve damage and foot problems, sight problems and gum disease, and says that adults and children aged 12 or over will be offered diabetic eye screening every 1 to 2 years.

The Exeter team publishes clinical management resources including guidance on sulphonylurea transfer and on pregnancy. If you have MODY and are planning a pregnancy, discuss it with your diabetes team before you conceive.

The NHS lists the most common symptoms of diabetes as feeling thirsty all the time, peeing more than usual, feeling very tired and losing weight without trying, and advises asking for an urgent GP appointment or contacting NHS 111 if you or your child has any of them. Not everyone has symptoms, so people with a family history of diabetes under 25 should raise it with a GP.

If you have already been told you have type 1 or type 2 diabetes but diagnosed young, have a strong family history, or do not seem to fit the usual pattern, ask your GP or diabetes team whether MODY testing is appropriate.