Maturity-Onset Diabetes of Young - A Review

What Is Maturity-Onset Diabetes of Young?

Maturity-onset diabetes of the young (MODY) is an uncommon kind of diabetes caused by a genetic mutation that inhibits or restricts the body's ability to manufacture insulin. This type of diabetes, as the name implies, primarily affects young people, adolescents, and young adults. MODY is a kind of monogenic (single gene) diabetes, indicating a single gene mutation causes it. It is inherited in an autosomal dominant manner, which indicates only one copy of a mutated gene is required to induce the illness.

What Are the Symptoms?

MODY patients may exhibit moderate diabetes symptoms; these symptoms will likely develop progressively, so one may not initially experience any symptoms. Due to this, MODY is often undiagnosed until later in life or confounded in type 1 or type 2 diabetes.

Possible symptoms include:

• Frequent urination.

• Thirst and dehydration.

• Unclear vision.

• Multiple cutaneous (skin) infections.

• Multiple yeast infections.

• Individuals with MODY might have high levels of sugar several years before developing symptoms.

What Are the Different Types of MODY?

• HNF1-Alpha: This variant is responsible for about seventy percent of MODY cases. It causes diabetes by reducing the amount of insulin produced by the pancreas. Diabetes usually develops during adolescence or early adulthood, and individuals with HNF1-alpha MODY do not need insulin; instead, they can be controlled with tiny doses of Sulfonylureas (often used to treat type 2 diabetes).

• HNF4-Alpha: This variant of MODY appears less common than the other individuals who have inherited this genetic variant and are more likely to have been born weighing 9 pounds or more (about 4 kilograms). They may also have low blood sugar at birth or immediately after. Individuals with HNF4-alpha are typically treated with a Sulphonylurea tablet but may eventually need Insulin.

• HNF1-Beta: This kind of MODY can cause several complications, including renal cysts (kidney cysts), uterine abnormalities, gout (a condition caused by urate is a substance in the body that builds up and makes needle-shaped crystals in the joints), and diabetes. Diabetes normally develops later in life; insulin therapy, a nutritious and balanced diet, and frequent physical activity are usually required. HNF4-beta MODY additionally increases the risk of diabetes complications.

• Glucokinase:This gene assists the body in determining the high arterial glucose level. When a particular gene is not functioning normally, the body increases blood glucose levels. Glucose levels in the blood of individuals in glucokinase MODY tend to be slightly elevated compared to normal; it is typically detected through routine testing because there are typically no symptoms. There is no treatment necessary for glucokinase MODY.

• NEUROD1 (MODY 6): The development of the pancreas and neurons is impacted by the basic-loop-helix transcription factor mutation known as NEUROD1. The majority of people will need to be treated with insulin.

• PDX1 (MODY 4): PDX1 is a transcription factor that controls gene expression and controls how animals, fungi, and plants grow. It does this by controlling genes that control insulin and the growth of the pancreas.

• KCNJ11 (MODY 13) and ABCC8 (MODY 12): ABCC8 and KCNJ1 mutations are linked to various conditions, including neonatal diabetes. Neonatal diabetes may either be chronic or temporary, and it frequently recurs during adult life. Genetic variants have been associated with neonatal hypoglycemia caused by elevated insulin levels; while the condition is usually transient, the patient could get diabetes later in the future. Monitoring fetal growth throughout pregnancy, including blood glucose levels with newborns, can be critical in these situations. Diabetes patients often respond effectively to Sulfonylureas.

Except for glucokinase, all varieties of MODY pose a risk of long-term diabetes issues, so patients should eat a nutritious diet and remain physically fit to maintain good plasma cholesterol and glucose levels, which reduces the chance of difficulties.

What Is the Diagnostic Method?

Diabetes type 1 or 2 are incorrectly identified in approximately eighty percent of instances of MODY.

• Molecular Genetic Testing: It helps determine the mutation. Single-gene testing can be done for patients with a specific subtype, and thorough genomic testing can be used when traditional testing fails to find the mutation in a patient with clinically suggestive signs.

Non-obese patients with MODY should be taken into account if they had diabetes that was discovered at a young age (less than 30 years), intact pancreatic beta-cell function, no pancreatic beta-cell autoimmunity, and a significant family history of diabetes.

• Physical Examination - Besides urine microalbumin and lipid levels, the physical examination should always include testing for retinopathy (eye test) and neuropathy (neurological disease), as some forms of MODY can develop complications.

Certain forms of MODY can be associated with renal, hepatic, genitourinary, pancreatic, or intestinal effects, a thorough review of the patient's medical history of all systems, and an inquiry into any known medical problems involving other organ systems.

• Genetic Testing- The genealogy of an individual's ancestors provides a few of the most valuable information. Patients with MODY have at least three generations of diabetes in their family tree. The diabetes diagnosis details for each family member should be their age of onset, physical habitus at the time of diagnosis, and insulin use history. Prior genetic testing within the family can be extremely useful.

What Is the Treatment Method?

Treatment for MODY is based on accurate diagnosis. Depending on the gene mutation, the optimal therapy for diabetes caused by MODY differs. Thus, comprehending the treatment and prognosis for these patients requires knowledge of the genetic subtype. The most common MODY subtype treatments are discussed below:

• MODY 2 (GCK)- In MODY 2 (GCK), patients with elevated fasting blood glucose do not typically develop postprandial hyperglycemia due to adequate insulin secretion in reactions to elevated glucose levels. Generally, these patients only require lifestyle and dietary modifications.

• MODY 3 (HNF1A) and MODY 1 (HNF4A) - MODY 3 (HNF1A) and MODY 1 (HNF4A) patients can typically be initially managed with dietary adjustments alone. These individuals do experience post-meal hyperglycemia following the consumption of carbohydrates. They may experience gradual beta cell degeneration over time and may need treatment. Sulfonylureas usually work well for these patients.

• MODY 5 (HNF1B) - Most of the time, sulfonylureas do not work effectively for individuals with MODY 5 (HNF1B). Concurrent hepatic insulin resistance may be present; thus, these patients need insulin regularly to manage their hyperglycemia. Microvascular problems, mainly in tissues where glucose uptake occurs without insulin activity, have been seen in a subset of MODY patients. Since the majority of these patients experience problems with their kidneys by age 45 and have the potential to develop end-stage kidney disease, it is crucial to monitor their renal function in particular closely.

What Is Management During Pregnancy?

Unless pregnant, GCK MODY rarely requires therapy. The fetus's abdominal circumference during the second trimester determines the mutation. If this score exceeds 75 percent, the baby will not possess the GCK mutation, and these women must administer insulin to avoid macrosomia. If the fetus's belly circumference is less than 75 percent, that does not contain the gene since it has a glucose setpoint similar to the mother, which has been increased. As the fetus perceives hyperglycemia as normal, insulin treatment is unnecessary and may even limit growth.

What Are the Complications of the Condition?

MODY, like other forms of diabetes, causes elevated blood sugar levels. Over time, not receiving treatment can contribute to complications such as:

• Nerve injury.

• Cardiac disease.

• Ocular harm, including blindness.

• Foot issues.

• Skin conditions, including infections.

Conclusion

MODY refers to a very specific set of diabetes disorders that are quite rare. They tend to appear in younger people since they are associated with the age group. They are brought on by a single alteration in a person's genetic code that reduces the quantity of insulin the individual generates.

Diabetes can take many forms, the most prevalent of which being types 1 and 2. These variants of the disease are distinct from other forms. Genetic testing is required to ascertain whether a person possesses a MODY subtype. This is important for a diagnosis to be made. Oral drugs, such as sulfonylureas, may be used to treat most cases, although treatment varies depending on the subtype of diabetes being treated.