What is Maturity Onset Diabetes of the Young (MODY)?


Diabetes is a common health problem that affects many people around the world. It happens when your body can’t properly control the amount of sugar (or glucose) in your blood.

Glucose is what gives energy to your cells, but to get into these cells, it needs a hormone called insulin. This insulin is made by an organ in your body called the pancreas.

There are various kinds of diabetes, each with different causes and ways to manage them. One of the least common types is called maturity onset diabetes of the young, or MODY.

MODY is a type of diabetes called monogenic diabetes as it is caused by a single gene change affecting how insulin is produced or released in your body.

Usually, MODY appears before the age of 25, and it can affect anyone, regardless of their weight, lifestyle, or ethnicity.

MODY is often mistaken for other types of diabetes, like type 1 or type 2, because it shares some of the same symptoms.

However, MODY has its own unique features and needs specific ways to manage it. Therefore, it’s important to understand what MODY is, how it’s different from other types of diabetes, and how to best treat it.

Let’s explore MODY in details!

Understanding MODY Diabetes

Besides type 1, type 2, and gestational diabetes, there are less common types of diabetes, like Maturity onset diabetes of the young (MODY).

This is a rare form of monogenic diabetes that happens because of a genetic change that affects the pancreas’s ability to produce insulin.

MODY is passed down in families, meaning if one of your parents has a gene for MODY, you can also get MODY before age 25.

This gene affects beta cells in our pancreas which are crucial for regulating our blood sugar levels.

MODY Diabetes is different from other types of diabetes in a few ways:

  • MODY Diabetes often affects kids, teenagers, and young adults. It usually shows up before the age of 25. This is different from type 1 and type 2 diabetes, which often appear later in life.
  • This kind of diabetes, MODY, is passed down through families in a way that means you only need a change in one gene to get it. This is different from type 1 and type 2 diabetes, where a mix of changes in several genes and environment factors can lead to the disease.
  • Depending on how severe MODY is and the particular type, it might not need to be treated with insulin. Some people with MODY Diabetes can keep their blood sugar levels in check with pills or changes to their lifestyle. This is different from type 1 diabetes, which always requires insulin injections, and type 2 diabetes, which may also need insulin over time.
  • MODY Diabetes may have symptoms that are not as severe or can change more than other types of diabetes, which can make it harder to diagnose. Some people with MODY may not have any symptoms and are diagnosed by accident or when relatives are screened. Others may have the usual diabetes symptoms, such as feeling very thirsty and peeing a lot, feeling tired, blurry vision, and losing weight.

When it comes to the genes involved in MODY, the changes or mutations are in genes that control how much insulin is made or released by the beta cells.

Current research suggests that changes in at least 14 genes can lead to MODY. But, some gene changes are more common than others.

Diabetes genetics

The four most usual types of MODY come from changes in these genes:

  • GCK-MODY (MODY 2): This is caused by a change in the GCK gene, which creates an enzyme that helps control how much glucose is in your body. People with GCK-MODY have slightly high, but stable, blood sugar levels that usually don’t need treatment.
  • HNF1A-MODY (MODY 3): This is caused by a change in the HNF1A gene, which helps control genes in the liver and pancreas. People with HNF1A-MODY have high blood sugar levels that gradually get worse but respond well to low doses of a type of diabetes medicine called sulfonylureas, which help to stimulate insulin secretion.
  • HNF4A-MODY (MODY 1): This is caused by a change in the HNF4A gene, which also helps control genes in the liver and pancreas. People with HNF4A-MODY have similar symptoms to those with HNF1A-MODY, but they may also have been born with low weight and had low blood sugar levels when they were babies.
  • HNF1B-MODY (MODY 5): This is caused by a change in the HNF1B gene, another gene that controls genes in the liver and pancreas. People with HNF1B-MODY have varying levels of high blood sugar and may also have abnormalities in their kidneys, like cysts or malformations.

There are several types or subtypes of MODY, each one caused by different gene changes. Each subtype has its own features, like:

  • The age at which it starts: Some subtypes appear earlier than others, ranging from infancy to adulthood.
  • How severe the high blood sugar is: Some subtypes cause mild and stable high blood sugar, while others cause severe and increasing high blood sugar.
  • How they respond to treatment: Some subtypes can be treated with pills or lifestyle changes, while others need insulin injections or other treatments.
  • The risk of complications: Some subtypes have a higher chance of leading to long-term problems of diabetes, such as kidney disease, eye disease, nerve damage, and heart disease.

The table below gives a summary of the main features of the different subtypes of MODY that we’ve found so far (MODY 1-14):

SubtypeGeneWhen it startsHow severe is the high blood sugarHow it responds to treatmentRisk of complications
MODY 1HNF4AFrom early childhood to adulthoodModerate to severePills or insulinHigh
MODY 2GCKFrom infancy to adulthoodMild and stableNo treatment or pillsLow
MODY 3HNF1AFrom childhood to adulthoodModerate to severePills or insulinHigh
MODY 4IPF1From infancy to childhoodSevereInsulinHigh
MODY 5HNF1BFrom infancy to childhoodSevereInsulin or other treatmentsHigh
MODY 6NEUROD1From childhood to adulthoodModerate to severePills or insulinHigh
MODY 7KLF11From childhood to adulthoodModerate to severePills or insulinHigh
MODY 8CELFrom childhood to adulthoodModerate to severePills or insulinHigh
MODY 9PAX4From childhood to adulthoodModerate to severePills or insulinHigh
MODY 10INSFrom infancy to childhoodSevereInsulinHigh
MODY 11BLKFrom childhood to adulthoodModeratePills or insulinHigh
MODY 12ABCC8From infancy to childhoodSevereInsulinHigh
MODY 13KCNJ11From infancy to childhoodSevereInsulin or pillsHigh
MODY14APPL1Age varies
Severity varies
Treatment varies
Risk varies

MODY Diabetes Symptoms and How It’s Diagnosed

MODY Diabetes often passes from one generation to the next in families, and it usually appears in people who are younger than 35 years old.

Common signs that you might have MODY Diabetes

The signs that someone has MODY Diabetes can change depending on which gene has been altered.

In some cases, there might be no signs at all. However, generally speaking, the symptoms of MODY Diabetes are usually not severe and appear slowly over time.

You might have high blood sugar levels for a number of years before you start to notice these symptoms:

  • Feeling thirsty or hungry more often than usual
  • Needing to pee a lot
  • Getting dehydrated
  • Having blurry vision
  • Getting infections regularly, like skin and yeast infections
  • Losing weight
  • Feeling tired all the time

How MODY Diabetes is different from other types of diabetes

MODY Diabetes can be mistaken for other types of diabetes, like Type 1 and Type 2, because they all share similar symptoms.

However, there are some things that can help you tell MODY Diabetes apart from the other forms of diabetes:

  • MODY Diabetes is something you inherit, so you probably have a lot of family members across different generations who also have diabetes.
  • MODY Diabetes isn’t associated with being overweight or having high blood pressure, so you’re likely to be a healthy weight and have normal blood pressure.
  • MODY Diabetes usually appears when you’re a teenager or a young adult, but it can show up at any age.
  • Depending on what type of gene change you have, you might not need insulin treatment if you have MODY Diabetes.

Other Types of Diabetes

The main types of diabetes are:

  • Type 1 diabetes: This happens when your immune system mistakenly attacks and destroys the cells in your pancreas that produce insulin. People with type 1 diabetes need to take insulin injections or use an insulin pump to keep their blood sugar levels under control.
  • Type 2 diabetes: This happens when your body doesn’t respond well to insulin or doesn’t make enough of it. People with type 2 diabetes might need to take pills or insulin injections to lower their blood sugar levels. They can also help control their diabetes by losing weight, eating healthy foods, and getting regular exercise.
  • Gestational diabetes: This happens when women who are pregnant develop high blood sugar levels because of changes in hormones that affect how insulin works. Gestational diabetes usually goes away after the baby is born, but it can increase the risk of developing type 2 diabetes later in life.

How doctors diagnose MODY Diabetes

If you have symptoms of diabetes or a routine blood test shows that you have high levels of sugar in your blood, your doctor might think you have diabetes.

The next step is to figure out what type of diabetes you have. Your doctor will ask about your family’s history with diabetes and might order some tests to rule out other types of diabetes and confirm if you have MODY Diabetes:

  • C-peptide test: This test measures how much insulin your body makes. People with Type 1 diabetes have low or undetectable levels of C-peptide, while people with MODY Diabetes have normal or slightly reduced levels.
  • Autoantibody test: This test looks for antibodies that attack your own insulin-making cells. People with Type 1 diabetes have positive autoantibody tests, while people with MODY Diabetes have negative tests.
  • Genetic test: This is the final test for MODY Diabetes. It involves taking a sample of your saliva or blood and sending it to a lab that can look for changes in the genes that cause MODY Diabetes.

A genetic test can also help identify which type of MODY Diabetes you have, as there are different types depending on which gene is affected. This can help determine the best treatment for your condition.

Health Problems Linked to MODY Diabetes

If MODY Diabetes isn’t treated properly or at all, it can cause high blood sugar levels. Over time, high blood sugar levels can damage different organs and tissues in your body, leading to serious health problems.

Here are some of the health problems that can show up quickly if you have MODY Diabetes:

  • Dehydration: High blood sugar levels make you pee a lot, which can make you lose fluids and electrolytes from your body. This can make you feel thirsty, give you a dry mouth, a headache, make you feel dizzy, and weak.
  • Ketoacidosis: This is a dangerous condition that happens when your body breaks down fat for energy instead of sugar. This produces acids called ketones that build up in your blood and urine. This can make you feel nauseous, vomit, give you stomach pain, fruity breath odor, confusion, and even cause you to fall into a coma.
  • Hypoglycemia: This is when your blood sugar level falls too low. This can happen if you take too much insulin or oral medication for your diabetes, skip meals, exercise too much, or drink alcohol. This can make you feel shaky, sweaty, hungry, irritable, drowsy, and even cause you to faint.

And here are some of the health problems that can develop over a longer period of time if you have MODY Diabetes:

  • Nerve damage: High blood sugar levels can damage the nerves that control sensation and movement in your body. This can make you feel tingling, numbness, pain, or weakness in your feet, legs, hands, or arms. It can also affect your digestion, bladder, sexual function, and heart rate.
  • Heart disease: High blood sugar levels can increase your risk of developing high blood pressure, high cholesterol, and atherosclerosis. These conditions can damage your blood vessels and reduce blood flow to your heart. This can lead to chest pain, heart attack, or stroke.
  • Eye damage: High blood sugar levels can damage the small blood vessels in your eyes. This can cause blurred vision, cataracts, glaucoma, or diabetic retinopathy. Diabetic retinopathy is a condition where the retina becomes swollen and leaks fluid or bleeds. This can lead to vision loss or blindness.
  • Foot problems: High blood sugar levels can damage the nerves and blood vessels in your feet. This can cause poor circulation, infections, ulcers, or gangrene. In severe cases, amputation may be necessary.
  • Skin problems: High blood sugar levels can affect your skin’s ability to heal and fight infections. This can cause dryness, itching, cracking, or fungal infections. You may also develop skin tags, dark patches, or blisters.

The importance of catching MODY Diabetes early to avoid these health problems

Finding out that you have MODY Diabetes early on is important because it can help you get the right treatment and prevent or delay these health problems from developing.

Detecting MODY Diabetes early involves getting a genetic test if your family has a history of diabetes or if you have symptoms that aren’t typical for your diagnosis.

The right treatment for MODY Diabetes depends on what type you have. Some types of MODY Diabetes might not need any treatment, while others might need insulin shots or oral medications.

The goal of treatment is to keep your blood sugar levels within a healthy range and avoid episodes of low blood sugar or ketoacidosis.

Keeping your blood sugar levels within a healthy range can help prevent or delay damage caused by high blood sugar levels to your organs and tissues. It can also help lower your risk of developing other health problems like high blood pressure, high cholesterol, or obesity.

By catching MODY Diabetes early and following the right treatment and lifestyle plan, you can improve your quality of life and avoid or delay the serious health problems that are linked to MODY Diabetes.

How To Manage and Treat MODY

How is MODY treated medically?

The medical approach to MODY is reliant on the kind of MODY and the patient’s individual traits. The main aim of treating MODY is to have better control of blood sugar levels, reduce the risk of complications and episodes of low blood sugar, and provide accurate genetic counseling.

For patients with mutations in the GCK gene (resulting in MODY 2), treatment is usually not needed as they experience only mild and stable high blood sugar levels, which do not negatively affect their life expectancy or quality of life.

diabetes management

However, treatment might be required during pregnancy if the baby does not inherit the mutation, as there’s a risk of the baby growing excessively in the womb (macrosomia) or experiencing low blood sugar levels after birth (neonatal hypoglycemia).

Patients with mutations in the HNF4A (leading to MODY 1) and HNF1A (leading to MODY 3) genes, resulting in defective insulin secretion and gradually increasing high blood sugar, are advised to take oral hypoglycemic agents (OHA), particularly sulfonylureas.

These medications stimulate insulin release from the pancreas and effectively lower blood sugar levels.

However, during pregnancy, sulfonylureas should be avoided as they can cross the placenta and cause low blood sugar in the fetus. Instead, insulin therapy might be preferred for pregnant women dealing with MODY 1 or MODY 3.

Recent studies suggest that other OHAs, such as metformin, DPP-4i, GLP-1RA, and SGLT2i, might be effective in patients dealing with MODY 1 or MODY 3.

These drugs work in various ways to improve blood sugar control, either by improving insulin sensitivity, increasing certain hormones, or reducing sugar reabsorption in the kidneys. However, more research is needed to confirm their long-term safety and effectiveness in MODY patients.

The other types of MODY are even rarer, and there’s very limited information available on how they should be treated. Here are a few examples:

  • Patients with mutations in the HNF1B gene (resulting in MODY 5) often require different treatments, as they may have other health problems unrelated to blood sugar levels, such as kidney disease, pancreatic atrophy, or genital malformations. They might need insulin therapy, kidney replacement therapy, or surgery depending on their condition.
  • Patients with mutations in the ABCC8 or KCNJ11 genes (leading to MODY 12 or 13) may respond well to sulfonylureas or other drugs that influence potassium channels in pancreatic beta cells. These drugs can restore insulin secretion and normalize blood sugar levels in some cases.
  • Patients with mutations in the BLK gene (leading to MODY 11) might benefit from metformin therapy as they have reduced insulin sensitivity as well as impaired insulin secretion. Metformin can improve insulin activity and lower blood sugar levels by reducing sugar production in the liver and increasing sugar uptake in the body.

How can lifestyle changes help in managing MODY?

Making changes to your lifestyle is crucial for all diabetes patients, including those with MODY. Such modifications can help better control blood sugar levels, prevent or delay complications, and enhance overall health and well-being.

Some examples of such modifications include:

  • Consuming a balanced diet that’s low in saturated fat, salt, and added sugars, and rich in fiber, fruits, vegetables, and whole grains. A dietitian can help design a personalized meal plan that suits the nutritional needs and preferences of each patient.
  • Regular physical activity that suits the age, fitness level, and medical condition of each patient. Physical activity can help lower blood sugar levels, improve insulin sensitivity, reduce heart disease risk factors, and promote mental health. A doctor can suggest the type, intensity, duration, and frequency of exercise that’s suitable for each patient.
  • Regularly monitoring blood sugar levels and adjusting treatment accordingly. Blood sugar monitoring can help evaluate the effectiveness of treatment, detect low or high blood sugar levels, and guide decisions about self-management. A doctor can recommend the best target range, frequency, and method of blood sugar monitoring for each patient.
  • Quitting smoking and limiting alcohol intake. Smoking and alcohol can worsen blood sugar control, increase the risk of complications, and harm overall health. A doctor can provide support and resources to help patients quit smoking or reduce alcohol consumption.
  • Managing stress and dealing with emotions. Stress and emotions can affect blood sugar levels, as well as mental health and quality of life. Patients with MODY may face additional challenges such as genetic testing, family issues, or social stigma. A doctor or a counselor can help patients develop healthy coping skills and access emotional support.

The importance of personalized medicine in treating MODY

Personalized medicine is an approach that tailors medical care to the individual characteristics of each patient, such as their genetic makeup, lifestyle, and preferences.

Personalized medicine can play a crucial role in treating MODY as it can help:

  • Identify the specific type of MODY and its associated features by performing genetic testing. This can confirm the MODY diagnosis, differentiate it from other types of diabetes, predict the clinical course and prognosis, and inform about the treatment options.
  • Choose the best treatment for each type of MODY based on the molecular mechanism and the response to therapy. For instance, patients with GCK-MODY might not need treatment at all, while patients with HNF1A-MODY or HNF4A-MODY might respond well to sulfonylureas or other OHAs.
  • Prevent unnecessary or harmful treatments that might not work or cause side effects for certain types of MODY. For instance, patients with GCK-MODY might avoid insulin therapy that could cause low blood sugar or weight gain, while patients with HNF1A-MODY or HNF4A-MODY might avoid sulfonylureas during pregnancy that could cause low blood sugar in the fetus.
  • Provide genetic counseling and screening for family members who might be at risk of inheriting or passing on the mutation that causes MODY. Genetic counseling can help patients and their relatives understand the implications of MODY, the inheritance pattern, the testing options, and the reproductive choices.

Even though personalized medicine is still developing and has some limitations, it can greatly help in the management of MODY.

Final Thoughts

MODY is a inherited form of diabetes that happens due to mutations in single genes affecting insulin production.

It has 14 known types, each differing in their clinical features and treatment options. Treatment varies depending on the type of MODY and may include OHAs (especially sulfonylureas), insulin therapy, or no treatment at all.

Lifestyle modifications are essential for all patients with MODY to improve their health and well-being.

MODY is an uncommon but important form of diabetes that deserves more attention and awareness. It can affect people of any age and ethnicity. It can have a significant impact on the quality of life and health outcomes of patients and their families.


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