You know your type 1, 2 and maybe even 3…but have you heard of MODY?

Mature Onset Diabetes of the Young is a rare form of diabetes that generally presents in people under the age of 25. Because of how rare it is, it is often misdiagnosed as another form of diabetes. New guidelines aim to change that. MYKE BARTLETT writes.

Diabetes educator Tara Savage says that, in her years of working on the Diabetes WA Telehealth service, she’s probably only met two people with MODY.

“One had already been diagnosed and the other was diagnosed by our endocrinologist,” Tara says. “That shows you how often it crops up, it’s certainly not an everyday thing.”

While diagnoses of type 1, type 2 and gestational diabetes are common, estimates from the UK suggest that only 1-2% of people living with diabetes have been diagnosed with MODY. But that figure may be an underestimate, as a lack of awareness about the condition means that, nine out of 10 times, people living with it are misdiagnosed.

Maturity Onset Diabetes of the Young (MODY) is a rare form of diabetes that runs strongly within families. It’s caused by a mutation in a single gene and, if a parent carries this mutation, their child has a 50% chance of inheriting it. Typically, those with MODY will develop diabetes before the age of 25, regardless of factors like weight or lifestyle. Getting a correct diagnosis can be difficult, as MODY often presents in a similar fashion to other types.

“They usually present young and probably a bit younger than you’d expect for type 2,” Tara says. “But they could be carrying some extra weight, so a GP might assume it’s type 2 and start them on oral medications, only for them to prove ineffective.”

These diagnoses are further complicated by the fact that there are different varieties of MODY, some which tend to quickly require insulin therapy and some that can be managed by other means. Genetic testing is the only way to ascertain a correct diagnosis – which can be important for both the patient and other family members who may be at risk – but this testing can be expensive and isn’t currently covered by Medicare. It’s also only available in Australia in a few specialised laboratories. Australian health professionals have been relying on guidelines from the UK which identify people at risk of a MODY diagnosis, but there is some question about whether they are effective for people from non-European background.

Professor Tim Davis was part of a study that investigated how common MODY is in Australia, drawing on a sample of 1668 people living with diabetes in the Fremantle area. The study suggested that one in every 280 Australians diagnosed with diabetes had a monogenic variety (which includes permanent neonatal diabetes as well as MODY). Another study, conducted in 2022, looked at Australians with diabetes who seemed to fit the criteria for MODY and discovered 21% of them had been misdiagnosed.

There is currently no national consensus on the guidelines for MODY testing, but Tim has recently contributed to a submission on new Australian guidelines (that is yet to be published). He hopes these guidelines will raise awareness of the condition and help make sure people are put on the correct treatment pathway.

“It is important we have guidelines that Australian clinicians can follow, given that there are between country differences and within country differences in key services related to diagnosis and management of monogenic diabetes,” Tim says. “The guidelines are there so health professionals who are dealing with these sorts of patients can have an idea about what forms of monogenic diabetes exist, what the clinical features are, what the diagnostic tests are and what management might be directed to them.”

Better awareness and clearer guidelines should help ensure people are getting the care and support they need. Most patients with MODY – some of whom will have been misdiagnosed with type 1 diabetes – will not require insulin injections and can be managed with simple oral medication. Others might not even require therapy at all. In short, when MODY is incorrectly diagnosed, it can lead to unnecessary and risky treatment.

The 2022 study quoted a participant who had originally been diagnosed with type 1 diabetes more than a decade earlier.

“The realisation that I could have had an oral medication, once daily for the past 11 years, instead of spending the time, mental and emotional toll, with physical and environmental impact of [approx.] 28,000 insulin injections that could have been completely avoided and the [approx.] 30,000 blood glucose level checks that could have been significantly minimised was (and still is) overwhelming,” she said.

Early consideration of MODY in patients newly diagnosed with diabetes is crucial for ensuring that the right treatment is in place from the outset. Given the genetic component, the impact of a correct MODY diagnosis can also extend beyond a single patient. Tim says he knows of one patient whose diagnosis led to the patient’s father having his medication routine changed.

“Early diagnosis of MODY means you can reassure a patient that their diabetes is not lifestyle-related,” Tim says. “It’s a genetic condition that they can’t undo and it has implications for first degree relatives, including planning pregnancy in people who are affected because there may be potential implications for the baby.”

This sort of genetic testing is called cascade testing, which tends to be cheaper because the type of MODY has already been identified. The authors of the 2022 study argued for testing to be covered by Medicare, which would not only benefit patients but could also save the healthcare system money in the long term, avoiding unnecessary treatments, reducing complications and preventing long-term hospital admissions.

Tim says he thinks it won’t be too long before Medicare does offer rebates on this genetic testing, although it is likely to be available only to those identified as being high-risk for MODY, or possibly via a referral from a specialist.

“You would have to show the lab that there was a high pre-test probability. It wouldn’t be a test that your GP could request, just on the basis of excluding MODY.”

An online calculator available at diabetesgenes.org can help people assess their own probability of MODY, but it’s something specialists are increasingly considering.

“I think endocrinologists would be suspicious if there was a strong family history of diabetes and occurrence in a young person who wasn’t particularly overweight and didn’t have any other risk factors.”

Tara says, while a MODY diagnosis is pretty unlikely, even if you’ve already been diagnosed with another type of diabetes, it’s important to know that it’s a possibility.

“People should know that it’s an option, because there’s a lot people don’t know about diabetes until they come to an education session like one of our DESMONDs,” Tara says. “People don’t realise, for example, that you can get type 1 at any age. It’s an autoimmune condition, so there’s no reason you can’t be diagnosed at 65 or 70. There’s always something new to learn.”

What is MODY?

MODY (Maturity Onset Diabetes of the Young) is a rare, inherited form of diabetes that affects a small percentage of Australians. Unlike type 1 or type 2 diabetes, MODY is caused by a single gene mutation, meaning there is a 50% chance of passing it on to children. Typically, those with MODY are diagnosed before the age of 25 and may be treated with medications or sometimes may not require medical treatment. In Australia, many people with MODY are initially misdiagnosed with type 1 or type 2 diabetes due to its rarity – MODY is believed to account for just 1-2% of diabetes cases globally. However, experts estimate that around 90% of MODY cases are not accurately diagnosed at first, leading to incorrect treatments.

The most common types of MODY include HNF1-alpha, which can be treated with oral medications, and HNF4-alpha, often requiring insulin later in life. Genetic testing is crucial for proper diagnosis and management. For Australians who suspect they have MODY, it’s essential to seek advice from their healthcare provider and consider genetic testing. Understanding this condition can lead to better treatment and awareness within families, who may also be at risk.

What about type 3 diabetes?

MODY is not type 3 diabetes. To make things more complex, there are two distinct varieties of type 3, which arise from different causes.

Type 3 diabetes is an unofficial term researchers use to describe a possible link between insulin resistance in the brain and Alzheimer’s disease. The brain, like other parts of the body, relies on insulin to help cells absorb glucose for energy. In type 3 diabetes, the brain becomes resistant to insulin, leading to reduced glucose uptake, which may contribute to cognitive decline, including memory loss and confusion. This condition is often called “diabetes of the brain.” Studies have found that individuals with type 2 diabetes are at a higher risk of developing Alzheimer’s, which has led to increasing interest in this connection.

Type 3c diabetes is caused by damage to the pancreas, the organ responsible for producing insulin and digestive enzymes. This type of diabetes can occur due to conditions like chronic pancreatitis, pancreatic cancer or even surgical removal of the pancreas. In type 3c, the pancreas is unable to produce enough insulin, leading to issues with blood glucose management. Additionally, the lack of digestive enzymes makes it difficult for the body to properly digest food, leading to symptoms such as unintentional weight loss, stomach pain and fatty stools. One of the key challenges with type 3c diabetes is that it’s often misdiagnosed as type 2 diabetes, since the symptoms can be similar. However, the critical difference lies in the cause: type 3c diabetes is directly linked to pancreatic dysfunction, while type 2 is typically related to insulin resistance throughout the body.

Common Types of MODY

• HNF1-alpha MODY: The most common form, responsible for 70% of MODY cases, it often appears in adolescence and is treatable with tablets rather than insulin.
• HNF4-alpha MODY: Linked to larger birth weight and low blood sugar at birth, this type may start with tablets but can progress to insulin.
• HNF1-beta MODY: Associated with kidney and uterine abnormalities, diabetes usually appears later