From the Guidelines
Maturity-Onset Diabetes of the Young (MODY) is a form of diabetes characterized by impaired insulin secretion with minimal or no defects in insulin action, inherited in an autosomal dominant pattern, and typically onset at an early age, classically before age 25 years.
Key Characteristics of MODY
- 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)
- HNF4A-MODY (MODY1) 1
Treatment Implications
- Genetic testing is warranted for individuals with MODY, as treatment implications are considerable 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
From the Research
Definition and Characteristics of Maturity-Onset Diabetes of the Young (MODY)
- MODY is a group of monogenic diseases characterized by autosomal dominant inheritance of a non-insulin-dependent form of diabetes that classically manifests in adolescence or in young adults under 25 years of age 2, 3, 4.
- It 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.
- MODY has a high degree of phenotypic and genetic polymorphism, with 14 identified subtypes 5, 6.
Causes and Forms of MODY
- The most prevalent forms of the disease are attributed to mutations in three genes: GCK (MODY 2) and (HNF)1A/4A (MODY 3 and MODY 1) 2, 3, 4.
- Mutations in the GCK gene result in asymptomatic, stable fasting hyperglycemia, which does not require specific treatment 2, 6, 4.
- Mutations in the HNF1A and HNF4A genes result in pancreatic β-cell dysfunction, which in turn causes hyperglycemia and can lead to diabetic angiopathy 2, 4.
Diagnosis and Treatment of MODY
- Accurate diagnosis of MODY is essential for optimal treatment and allows for early diagnosis for asymptomatic family members 2, 3, 4.
- The primary treatment for MODY is oral sulfonylureas, which are effective in patients with mutations in the HNF1A and HNF4A genes 2, 3, 6, 4.
- Insulin therapy may be required later in life for some patients due to the development of resistance to sulfonylurea drugs 2, 6.
- Gene therapy is still an experimental approach and is unlikely to be widely used in the clinic due to the peculiarities of MODY structure and high genetic polymorphism 2.