From the Guidelines
Maturity-Onset Diabetes of the Young (MODY) is a rare form of diabetes caused by single gene mutations that affect insulin production in the pancreas, typically developing before age 25 with mild to moderate high blood sugar levels and often misdiagnosed as type 1 or type 2 diabetes. According to the most recent and highest quality study 1, MODY is characterized by impaired insulin secretion with minimal or no defects in insulin action, inherited in an autosomal dominant pattern with abnormalities in at least 13 genes on different chromosomes identified to date. The most commonly reported forms are GCK-MODY (MODY2), HNF1A-MODY (MODY3), and HNF4A-MODY (MODY1).
Some key features of MODY include:
- Onset of hyperglycemia at an early age, classically before age 25 years
- Impaired insulin secretion with minimal or no defects in insulin action
- Inherited in an autosomal dominant pattern
- Abnormalities in at least 13 genes on different chromosomes identified to date
- The most commonly reported forms are GCK-MODY, HNF1A-MODY, and HNF4A-MODY
Treatment varies by subtype, with patients with GCK-MODY often not requiring medication, while those with HNF1A or HNF4A-MODY typically responding well to low doses of sulfonylureas rather than insulin 1. Accurate diagnosis through genetic testing is crucial as it leads to more appropriate treatment than what might be prescribed for type 1 or type 2 diabetes. MODY accounts for approximately 1-2% of all diabetes cases, and testing should be considered in young, non-obese patients with diabetes and a strong family history across multiple generations.
It's worth noting that while other studies 1 also discuss MODY, the most recent and highest quality study 1 provides the most up-to-date information on this condition.
From the Research
Definition and Characteristics of MODY
- Maturity-Onset Diabetes of the Young (MODY) is a rare form of diabetes with specific features that distinguish it from type 1 and type 2 diabetes 2, 3, 4, 5, 6.
- MODY is characterized by autosomal dominant inheritance, onset before 25 years of age, absence of β-cell autoimmunity, and sustained pancreatic β-cell function 4, 5, 6.
- There are 14 known subtypes of MODY, with mutations in three genes (HNF1A, HNF4A, GCK) accounting for about 95% of all MODY cases 2.
Diagnosis and Treatment of MODY
- Diagnosis of MODY is crucial for optimal treatment and genetic counseling, as it allows for the identification of the specific subtype and the most appropriate treatment approach 2, 3, 4, 5, 6.
- Treatment options for MODY vary depending on the subtype, with patients with GCK gene mutations often not requiring specific treatment, while those with HNF1A and HNF4A gene mutations may require oral hypoglycemic agents or insulin therapy 2, 3, 6.
- Sulfonylureas are effective in patients with HNF1A and HNF4A gene mutations, but insulin therapy may be required later in life 3, 6.
Subtypes of MODY
- The most common subtypes of MODY are caused by mutations in the GCK, HNF1A, and HNF4A genes, accounting for almost 80% of cases 5.
- MODY 2, caused by GCK gene mutations, results in mild, asymptomatic, and stable fasting hyperglycemia, usually requiring no specific treatment 3, 6.
- MODY 1 and MODY 3, caused by HNF4A and HNF1A gene mutations, result in progressive pancreatic β-cell dysfunction and hyperglycemia, which can lead to microvascular complications 3, 6.