What is Maturity Onset Diabetes in the Young?
In 1974, a condition called mature onset diabetes of the young (MODY) was defined. MODY is a common type of diabetes that is passed down through families. Often, people with MODY may be misdiagnosed as having type 1 or type 2 diabetes. This condition usually appears before someone turns 25. Unlike other types of diabetes, MODY does not trigger a harmful condition called ketoacidosis, and patients do not have certain autoantibodies, which are immune system proteins that attack the body’s own tissues and organs. In simple terms, MODY occurs due to the poor functioning of insulin-producing cells in the pancreas.
Being aware and understanding of MODY is crucial for healthcare professionals. This is because this knowledge can help identify who should be tested for this condition. It’s also vital for patients and their families because MODY is hereditary. In addition, different gene mutations or changes causing MODY respond differently to treatments and have varying rates of complications. Moreover, some forms of MODY can come with abnormalities in other organs like the kidneys, liver, or intestines.
It’s worth noting that currently, there are six main types of MODY that we know of. But, as genetic testing develops and improves, more types are expected to be identified.
What Causes Maturity Onset Diabetes in the Young?
MODY, or Maturity Onset Diabetes of the Young, is caused by problems in the development of specific cells in the pancreas that affect the release of insulin, a hormone that controls blood sugar levels. This condition is usually inherited, meaning it’s passed down from parents to their children. People with MODY typically have changes in one copy of a gene, known as heterozygous mutations.
It’s important to note, however, that the effect and appearance of MODY can differ significantly, even among family members. The specific characteristics of MODY largely depend on which gene is involved.
The genes related to MODY influence how insulin is produced and released. This is typically due to problems with the cells sensing insulin, how sugar is used in the cell that produces insulin (beta cells), or issues related to the activation of a specific chemical process involving potassium channels that are dependent on a molecule called adenosine triphosphate (ATP).
Risk Factors and Frequency for Maturity Onset Diabetes in the Young
MODY, a form of diabetes, accounts for less than 5.0% of all diabetes cases. It is believed that 6.5% of children who have diabetes but show no antibodies, may actually have MODY. The disease generally starts between the ages of 10 to 40.
Patients with MODY show features similar to both type 1 and type 2 diabetes, causing it to be frequently misdiagnosed. Therefore, as doctors become more aware and diagnose MODY more frequently, we may see an increase in the number of acknowledged cases.
Despite being most commonly found in Caucasians, MODY has also been reported in other racial groups, including Asian Indians in South Africa.
Signs and Symptoms of Maturity Onset Diabetes in the Young
When discussing a person’s medical history, it’s essential to pay attention to specific details, especially if a diagnosis of MODY (Maturity Onset Diabetes of the Young) is being considered. This type of diabetes usually begins in teenagers or young adults. Therefore, understanding the details of their diabetes diagnosis is essential.
Birth history can also provide valuable information. For instance, individuals with HNF1B (MODY 5) may have had slow growth inside the womb and may have some birth defects, including problems with the kidneys, genital tract, or pancreas. Those with HNF4A (MODY 1) may have been born with a weight more than 800 grams above average and experienced high insulin and low glucose levels (neonatal hyperinsulinemic hypoglycemia) shortly after birth. Patients with GCK (MODY 2) may have had slightly high glucose levels when fasting at birth. Similarly, some individuals with HFN1A (MODY 3) could have experienced high insulin and low glucose levels after birth as well.
It’s also essential to learn about any known medical problems involving other organs, as some forms of MODY can cause effects outside of the pancreas, impacting the kidneys, liver, genitals, pancreas, or intestines.
Family history is also crucial, as MODY often runs in families and spans at least three generations. The details of the diagnosis in each family member, including the age of onset, body shape at diagnosis, history of insulin use, and any genetic testing that’s been performed, can provide useful information.
A physical examination won’t necessarily provide precise information that could lead to a MODY diagnosis or identify a specific subtype. Although patients with MODY are typically of normal weight, they can also be overweight. Therefore, in addition to regular check-ups, they should routinely be tested for complications of diabetes, like damage to the retina or nerves, in addition to routine urine protein levels and blood lipid tests.
Testing for Maturity Onset Diabetes in the Young
In 2008, guidelines were established to help diagnose a type of diabetes known as MODY. These guidelines state that if a family member was diagnosed under the age of 25 and the disease can be traced through at least two generations of the family, it suggests the presence of MODY. This type of diabetes usually doesn’t need insulin therapy as beta-cell antibodies are absent and the body still produces insulin, which is reflected in c-peptide levels above 200pmol/L.
The first step in evaluating a patient for MODY should be to rule out Type 1 Diabetes (DM1) by testing for pancreatic autoantibodies, which are specific proteins produced by the immune system that may attack the pancreas.
Particularly for a subtype of MODY known as GCK MODY, analyzing hemoglobin A1C (HbA1C) and fasting plasma glucose levels can help. For such patients, fasting plasma glucose typically range between 99-144mg/dL, and the range for HbA1C is about 5.6-7.3% if under 40 years old or 5.9-7.6% if above 40.
A high sensitivity C-reactive protein (hsCRP) test can also be used. This test measures the amount of a protein called C-reactive protein in your blood. The levels of this protein increase when there’s inflammation in your body. The test can help identify a subtype of MODY called HNF1A MODY (MODY 3), where hsCRP levels are commonly less than 0.75mg/L.
Another clue is if a patient with MODY has a high level of C-peptide – a substance made in the pancreas – during a period of high blood sugar, usually 0.6mg/dL or more.
Genetic testing for MODY should be done when there’s a high chance that the patient doesn’t have Type 1 or Type 2 diabetes. This could potentially change how the disease is treated, or even if it needs treatment at all. However, because genetic testing can be costly and time-consuming, it’s important to have a set of criteria to identify those who should get this testing:
- The patient has a strong family history of diabetes developed between their 20s and 50s
- The patient is slim or lean
- The patient tests negative for autoantibodies
- The patient shows signs that don’t align with Type 1 or Type 2 diabetes, such as low renal threshold, unexpected rises in blood sugar, or lower than expected CRP levels
- The patient has lower than expected HDL-C (a type of cholesterol)
- The patient has high insulin sensitivity, though in some cases, insulin resistance has been noted in MODY
- Children diagnosed with Type 1 Diabetes who test negative for autoantibodies and display high C-peptide levels
If a specific gene mutation is suspected based on a patient’s symptoms or characteristics, the doctor may opt for single-gene testing. If it’s unclear, a multi-gene panel can be performed that covers 14 known genes associated with MODY.
Treatment Options for Maturity Onset Diabetes in the Young
The best treatment for diabetes linked to MODY (Maturity Onset Diabetes of the Young) depends on the specific gene mutation a patient has. That’s why it’s crucial to identify the genetic subtype to guide treatment decisions and predict outcomes.
For instance, folks with the MODY 2 mutation usually have high fasting blood glucose but don’t tend to have a sudden rise in blood glucose levels after meals (or ‘postprandial hyperglycemia’). This is because they still have a good enough insulin response to high glucose levels. Most of the time, they only need to adjust their lifestyle and diet.
As for the MODY 3 and MODY 1 mutations, dietary changes alone may be enough initially. Yet, such patients do experience a spike in blood sugar levels after intake of carbohydrate-rich food. Over time, their insulin-producing cells may begin to fail, and they might require medication. They usually respond well to a class of drugs called sulfonylureas. GLP-1RA (glucagon-like peptide 1 agonist), another type of medication, can also be beneficial. A study comparing GLP-1RA and glimepiride (a sulfonylurea) in MODY 3 patients found them equally effective in lowering blood glucose. Yet, glimepiride resulted in a slightly greater drop in glucose levels but potentially with an increased risk of low blood glucose (or ‘hypoglycemia’).
People with MODY 5 mutations may not respond to sulfonylureas the way others do. They usually need insulin to manage their high blood glucose levels. This group of patients also tends to experience complications related to their tiny blood vessels (‘microvascular complications’). It’s particularly important to keep an eye on their kidney function since many of them develop kidney problems by age 45 that can lead to advanced kidney disease.
Unfortunately, there aren’t many available guidelines for treating many of the MODY subtypes because the cases are rare.
In children and adolescents with MODY, the use of certain drugs varies by country. In most countries, metformin (a medication that reduces glucose production in the liver) and insulin are permitted. Certain countries allow the use of sulfonylureas in adolescents. However, most other oral diabetes medications haven’t been approved for under-18s.
Interestingly, GCK MODY generally doesn’t need treatment except during pregnancy. Treatment then is determined by the baby’s genetics. This isn’t established through genetic testing but instead by measuring the baby’s abdomen during the second trimester of pregnancy. If it’s larger than usual (measuring more than the 75th percentile), it suggests that the baby doesn’t have the GCK mutation. These mothers should receive insulin treatment to prevent the baby from growing too large. On the other hand, if the baby’s abdominal size is less than the 75th percentile, it likely means they carry the same gene mutation as the mother. Therefore, insulin treatment for the mother is not necessary and can even restrict the baby’s growth.
What else can Maturity Onset Diabetes in the Young be?
These are some conditions related to or causing high blood sugar levels:
- Type 1 diabetes mellitus
- Type 2 diabetes mellitus
- Chronic pancreatitis
- Cystic fibrosis
- Diabetic ketoacidosis (DKA)
- Diabetic nephropathy (kidney disease)
- Disorders of the body’s target tissues
- Other hormonal conditions
- Prolonged use of medications such as glucocorticoids
- Insulin resistance syndrome
- Lead-induced kidney problems
- Non-diabetic conditions causing abnormal presence of sugar in urine
- Renal glycosuria, another condition causing sugar presence in urine
- Secondary hyperglycemia, where high blood sugar is a result of another medical condition
What to expect with Maturity Onset Diabetes in the Young
Patients with MODY 2 (also known as GCK) usually have a good outlook because they have milder high blood sugar levels and fewer complications.
On the other hand, patients with MODY 3 (also known as HNF1A) tend to have complication rates and outlooks similar to those with type 1 and type 2 diabetes. This is the case with most types of MODY, except for MODY 2, which generally has the best outlook.
Finally, patients with MODY 5 (or HNF1B) are more likely to develop severe kidney disease that requires kidney replacement therapy that is not related to diabetic kidney disease. This happens because the gene affected in MODY 5 is involved in the development of multiple organs, including the kidneys.
Possible Complications When Diagnosed with Maturity Onset Diabetes in the Young
The complications patients face are dependent on their specific type of MODY (Maturity-Onset Diabetes of the Young), a form of diabetes caused by specific gene mutations. Each subtype has different potential complications:
- MODY 1 (HNF4A): Those affected can have vascular problems, including issues with blood vessels. They are also prone to high levels of lipids in their bloodstream and situations where the body’s metabolic processes don’t work properly, as this gene is expressed in the liver.
- MODY 2 (GCK): This subtype is less frequently associated with typical diabetes-related complications like microvascular issues (affecting tiny blood vessels) and macrovascular complications (affecting larger blood vessels).
- MODY 3 (HNF1A): Patients face a high risk of both small and large vessel complications similar to patients with type 1 and type 2 diabetes. These people typically exhibit high HDL-C (good cholesterol) and low hsCRP (a marker of inflammation), conditions usually associated with less risk, but still, they are at a high risk of heart disease. Therefore, it’s crucial to start these patients on cholesterol-lowering statins by the age of 40. This variant has also been associated with problems related to the pancreas’s enzyme-producing function.
- MODY 4 (PDX1): This rare type is connected to the absence of the pancreas at birth, early onset of diabetes in newborns, and dysfunction in the enzyme-producing segment of the pancreas.
- MODY 5 (HNF1B): In addition to diabetes, patients show congenital anomalies of the urinary tract and genital organs. This mutation is also associated with conditions like a bicornate uterus, Rokitanski syndrome, agenesis of the vas deferens, and hypospadias. Additionally, patients may have low magnesium due to kidney issues, kidney disease with gout, and hyperparathyroidism. Patients can have low birth rates due to decreased insulin secretion crimping growth before birth, and they can sometimes show resistance to insulin. Small blood vessel-related issues are also common.
- MODY 6 (NEUROD1): This variant leads to diabetes, neurological problems, and learning disabilities in children.
Preventing Maturity Onset Diabetes in the Young
MODY, short for Maturity Onset Diabetes of the Young, is a type of diabetes that is passed down through families. It’s important to note that different types of this condition can affect people differently. This is why it’s crucial for patients to understand how this disease works and why regular check-ups are necessary.
As it runs in families, learning about your family’s medical history can be incredibly useful for early detection and starting treatment before it leads to other health issues. Some patients might only need to make changes in their diet, but as the disease progresses, medication might be necessary. In addition, certain types of MODY can raise the risk of other health problems, so regular screenings and seeing specialists regularly is very important.
For women with MODY, especially those carrying the GCK mutation, they should know they might need insulin treatment during their pregnancy, based on their baby’s genetics. That’s why it’s especially important for them to have regular check-ins with a specialist during their pregnancies.
