From the Guidelines
MODY (Maturity-Onset Diabetes of the Young) 4,5, and 6 are rare forms of monogenic diabetes, each resulting from distinct genetic mutations.
Characteristics of MODY 4,5, and 6
- MODY 4 is caused by a mutation in the IPF1 gene 1
- MODY 5 is associated with a mutation in the HNF1B gene 1
- MODY 6 is caused by a mutation in the NEUROD1 gene 1
Treatment
Treatment for these forms of MODY typically involves lifestyle modifications, and in some cases, medication such as sulfonylureas, with a typical starting dose of 1.25-2.5mg of glipizide or 2.5-5mg of gliclazide, taken orally once or twice daily, with dose adjustments as needed to achieve optimal glycemic control 1.
Key Points
- A diagnosis of MODY should be considered in individuals who have atypical diabetes and multiple family members with diabetes not characteristic of type 1 or type 2 diabetes 1
- Genetic counseling is recommended to ensure that affected individuals understand the patterns of inheritance and the importance of a correct diagnosis and to address comprehensive cardiovascular risk 1
From the Research
Characteristics of MODY Types 4,5, and 6
- MODY type 5 is associated with pancreatic agenesis, renal abnormalities, genital tract malformations, and liver dysfunction due to mutations in the HNF1B gene 2
- MODY type 6 is a more severe subtype that requires an individualized treatment approach to maintain a patient's quality of life and prevent complications 3
- The characteristics of MODY type 4 are not explicitly described in the provided studies, but it is mentioned that MODY has 14 subtypes with differences in prevalence and complications occurrence, which tailor the therapeutic approach 3
- MODY subtypes differ based on the gene involved, gene penetrance, and expressivity, leading to varying clinical presentations and treatment requirements 3
Clinical Presentation and Diagnosis
- MODY can be missed due to its broad clinical presentation, and heightened vigilance and a low threshold for genetic testing are required in patients with a high likelihood of having MODY 4
- A precise molecular diagnosis is essential for optimal treatment of patients and allows early diagnosis for their asymptomatic family members 2
- Genetic testing can help identify patients who are most likely to benefit from molecular genetic testing and guide treatment decisions 5
Treatment and Management
- Sulfonylureas are effective in patients with certain MODY subtypes, such as MODY 1 and 3, by acting on adenosine triphosphate (ATP)-sensitive potassium channels 2
- Insulin therapy may be required later in life for patients with MODY, particularly those with more severe subtypes 2, 3
- An individualized treatment approach is necessary to maintain a patient's quality of life and prevent complications in MODY patients 3