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

From the Guidelines

Maturity-Onset Diabetes of the Young (MODY)

Maturity-Onset Diabetes of the Young (MODY) is a rare form of diabetes characterized by autosomal dominant inheritance and onset typically before the age of 25 1.

Key Characteristics

• Impaired insulin secretion with minimal or no defects in insulin action (in the absence of coexistent obesity) 1
• Inherited in an autosomal dominant pattern with abnormalities in at least 13 genes on different chromosomes identified to date 1
• The most commonly reported forms are GCK-MODY (MODY2), HNF1A-MODY (MODY3), and HNF4A-MODY (MODY1) 1

Management

• Management of MODY depends on the specific subtype, with some forms responsive to sulfonylureas such as glyburide or glipizide, while others may require insulin therapy 1
• Patients with GCK-MODY exhibit mild, stable fasting hyperglycemia and do not require antihyperglycemic therapy except sometimes during pregnancy 1
• Patients with HNF1A- or HNF4A-MODY usually respond well to low doses of sulfonylureas, which are considered first-line therapy 1

Genetic Testing

• Genetic testing is recommended for individuals with suspected MODY, especially those with a family history of diabetes not characteristic of type 1 or type 2 diabetes 1
• Consultation with a center specializing in diabetes genetics is recommended to understand the significance of genetic mutations and how best to approach further evaluation, treatment, and genetic counseling 1

From the Research

Definition and Characteristics of Maturity-Onset Diabetes of the Young (MODY)

• Maturity-Onset Diabetes of the Young (MODY) is a group of monogenic disorders characterized by autosomal dominantly inherited non-insulin dependent form of diabetes, classically presenting in adolescence or young adults before the age of 25 years 2, 3.
• MODY is a rare cause of diabetes, accounting for 1% of all cases, and is often misdiagnosed as type 1 or type 2 diabetes 2, 3, 4, 5.
• The disease has a high degree of phenotypic and genetic polymorphism, with 14 identified subtypes, each with different prevalence and complications occurrence 4, 5.

Clinical and Laboratory Characteristics

• Mutations in the glucokinase (GCK) (MODY 2) and hepatocyte nuclear factor (HNF)1A/4A (MODY 3 and MODY 1) genes are the most common causes of MODY 2, 3.
• GCK mutations cause a mild, asymptomatic, and stable fasting hyperglycemia, usually requiring no specific treatment 2, 3.
• Mutations in the HNF1A and HNF4A genes result in pancreatic β-cell dysfunction, causing hyperglycemia and potentially leading to microvascular complications 2, 3.
• Sulfonylureas are effective in treating MODY patients with HNF1A and HNF4A mutations, although insulin therapy may be required later in life 2, 3.

Diagnosis and Treatment

• A precise molecular diagnosis is essential for optimal treatment of MODY patients and allows for early diagnosis of asymptomatic family members 2, 3, 6.
• Molecular genetic testing is crucial for making a firm diagnosis of MODY, defining a follow-up plan, and reassuring patients' families 6.
• The treatment approach for MODY varies depending on the subtype, with some subtypes requiring lifestyle interventions alone, while others require individualized treatment to maintain quality of life and prevent complications 5.