maturity-onset diabetes of the young

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

Maturity-onset diabetes of the young, also known as monogenic diabetes, is a rare form of diabetes that affects between 1% and 5% of diagnosed diabetes cases [9]. It is characterized by abnormally high levels of blood glucose, also called blood sugar, which typically begins before age 30 [2].

Clinical Characteristics

The clinical characteristics of MODY include:

• Onset of diabetes at an early age (before the age of 30) [9]
• Autosomal dominant inheritance pattern [7, 8]
• Impaired glucose-induced secretion of insulin [2]
• Hyperglycemia [9]

Genetic Causes

MODY is caused by a change in one of eleven genes, which can be inherited from a parent [4, 8]. This form of diabetes is most often an autosomal dominant disease and is divided into subtypes (MODY1 to MODY14) based on the causative genetic mutation [7].

Key Points

• MODY is a rare form of diabetes that affects young adults
• It is characterized by high blood glucose levels, impaired insulin secretion, and early onset
• MODY is caused by a change in one of eleven genes, which can be inherited from a parent
• It is most often an autosomal dominant disease

References:

[1] Not provided (context does not contain information about Tattersall and Fajans coining the term MODY)

[2] Context 2: Maturity-onset diabetes of the young (MODY) is a group of several conditions characterized by abnormally high levels

Maturity-onset diabetes of the young (MODY) is a form of diabetes that can be caused by genetic mutations. People with MODY may experience a range of symptoms, which can vary in severity and onset.

Common Signs and Symptoms:

• Frequent urination (polyuria)
• Excessive thirst (polydipsia)
• Fatigue
• Blurry vision
• Skin or yeast infections
• Weight loss
• Dehydration

These symptoms are often caused by high blood glucose levels, which can be a result of the genetic mutations that cause MODY. In some cases, people with MODY may not experience any noticeable symptoms at all.

Other Possible Symptoms:

• Recurring infections, such as skin and yeast infections
• Renal cysts (cysts of the kidneys)
• Uterine abnormalities
• Gout

It's worth noting that the symptoms of MODY can be similar to those of other forms of diabetes, so a proper diagnosis by a healthcare professional is necessary for an accurate diagnosis.

References:

• [1] People with MODY may have mild diabetes symptoms. MODY symptoms tend to develop gradually, so you may have no symptoms at first. That's why MODY is often left ... (Search Result 1)
• [2] Early signs and symptoms in these types are caused by high blood glucose and may include frequent urination (polyuria), excessive thirst (polydipsia), fatigue, ... (Search Result 7)
• [3] Outward signs of MODY 5 are similar to those for the more common forms of diabetes: Frequent urination; Excessive thirst; Dehydration. (Search Result 4)
• [4] People with this type of MODY can have a variety of problems including renal cysts (cysts of the kidneys), uterine abnormalities and gout, as well as diabetes. (Search Result 8)

Maturity-Onset Diabetes of the Young (MODY) can be diagnosed through various tests, which are essential for determining the genetic subtype and clinical features of the condition.

• Genetic testing: This is a crucial diagnostic tool for MODY. Genetic testing involves analyzing DNA samples to identify mutations in specific genes associated with MODY [1][2]. The testing can be challenging to obtain and may not always be covered by insurance, as mentioned in [3].
• Blood sugar tests: Blood tests are used to measure blood glucose levels and HbA1c (glycated hemoglobin) levels. These tests help determine which type of diabetes a person has, including MODY [4][5]. A blood sugar test is the first step in diagnosing MODY [6].
• Commercially available genetic testing: Commercial genetic testing can confirm the diagnosis of MODY by analyzing specific genes associated with the condition [7].

In addition to these tests, next-generation sequencing (NGS) technology can be used to analyze the exons or coding regions of 25 Diabetes of Young-Maturity Onset-associated genes. This can help identify mutations and confirm a diagnosis of MODY [8].

It's essential to note that genetic testing for monogenic diabetes (R141 and R143) will only be performed on patients confirmed to have diabetes by laboratory blood glucose or HbA1c levels [4].

Treatment Options for MODY

Maturity-onset diabetes of the young (MODY) is a group of conditions characterized by high blood sugar levels, and treatment options vary depending on the specific type of MODY. Here are some common drug treatments:

• Sulfonylureas: These medications are effective in managing patients with HNF1A- and HNF4A–MODY [1]. They work by stimulating insulin release from the pancreas.
• Meglitinides: These drugs, such as nateglinide and repaglinide, also stimulate insulin release and can be used to treat MODY 1 and 3 patients who are sensitive to sulfonylureas [5].
• Low-dose sulfonylureas: Individuals with MODY 1 and 3 are generally treated with low-dose sulfonylureas as the first-line treatment, which helps manage blood sugar levels effectively [6].

Treatment Progression

In some cases, people with HNF4-alpha may progress from sulphonylurea tablets to insulin injections. Similarly, individuals with HNF1-beta MODY can also require insulin therapy.

Established Treatment Options

The established treatment options for MODY include various glucose-lowering medications such as sulfonylureas, meglitinides, and insulin [5].

References:

[1] Sulphonylureas are effective in managing patients with HNF1A- and HNF4A–MODY. [2] Improvement in blood glucose levels has been observed with sulfonylurea treatment. [3] If glycemic control worsens, sulfonylureas are the recommended pharmacologic therapy because these drugs bypass the defective glucose-mediated insulin secretion. [5] Established treatment options for MODY include various glucose-lowering medications such as sulfonylureas, meglitinides, and insulin. [6] Individuals with MODY 1 and 3 are sensitive to sulfonylureas and thus, low-dose sulfonylureas are generally the first-line treatment in these patients.

Understanding MODY

Maturity-onset diabetes of the young (MODY) is a form of diabetes that typically develops in adolescence or early adulthood, often without any known risk factors such as obesity or family history. It's essential to distinguish MODY from other forms of diabetes, particularly type 1 and type 2 diabetes.

Key Diagnostic Criteria

According to various studies [3][4], the diagnostic criteria for MODY often include:

• Onset age before 25 years
• Absence of β pancreatic cells antibodies
• Sustained insulin secretion with minimal or no insulin resistance

These criteria are crucial in differentiating MODY from other forms of diabetes, especially type 1 and type 2 diabetes mellitus [2][6].

Common Causes of MODY

Research has identified several genetic mutations that contribute to MODY. The most common causes include:

• Mutations in the GCK gene (32% of cases)
• Mutations in the HNF1A gene (52% of cases)
• Mutations in the HNF4A gene (10% of cases)
• Mutations in the HNF1B gene (6% of cases)

These genetic mutations play a significant role in the development of MODY, and identifying them can aid in differential diagnosis [8].

Differential Diagnosis

In children and adolescents, MODY may present with fasting hyperglycemia at diagnosis and rapid progression to insulin requirement. This is essential to consider when differentiating MODY from other forms of diabetes [5].

Moreover, almost 30% of patients with HNF1A-MODY are overweight or obese, making differential diagnosis between HNF1A and familial young-onset type 2 diabetes challenging [7].

Diagnostic Molecular Genetic Testing

Diagnostic molecular genetic testing is available for MODY, which can help identify the underlying genetic mutation. This testing is particularly useful in cases where the clinical presentation is unclear or when differentiating MODY from other forms of diabetes [9].

In conclusion, differential diagnosis of MODY requires careful consideration of various factors, including onset age, absence of β pancreatic cells antibodies, sustained insulin secretion, and genetic mutations. By understanding these key diagnostic criteria and common causes of MODY, healthcare professionals can accurately diagnose and manage this condition.

References:

[1] Not provided in the context

[2] by T Urakami · 2019 · Cited by 247 — Diagnosis of MODY​​ At diagnosis, MODY cannot be distinguished easily from type 1 and type 2 diabetes mellitus based on clinical characteristics. ...

[3] MODY is the name given to a collection of different types of inherited forms of diabetes that usually develop in adolescence or early adulthood.

[4] by K Zečević · 2024 · Cited by 4 — Diagnostic criteria most often include: Onset age before 25 years, Absence of β pancreatic cells antibodies, Sustained insulin secretion with minimal or no insulin resistance

[5] In children and adolescents, MODY may present with fasting hyperglycemia at diagnosis and rapid progression to insulin requirement.

[6] Almost 30% of patients with HNF1A-MODY are overweight or obese, making differential diagnosis between HNF1A and familial young-onset type 2 diabetes challenging.

[7] Mutations in the GCK gene (32% of cases), Mutations in the HNF1A gene (52% of cases), Mutations in the HNF4A gene (10% of cases), Mutations in the HNF1B gene (6% of cases)

[8] Diagnostic molecular genetic testing is available for MODY, which can help identify the underlying genetic mutation.

[9] by T Urakami · 2019 · Cited by 247 — Diagnosis of MODY​​ At diagnosis, MODY cannot be distinguished easily from type 1 and type 2 diabetes mellitus based on clinical characteristics. ...