What is Monogenic Diabetes (MODY)?
Monogenic diabetes, most commonly referred to as Maturity-Onset Diabetes of the Young (MODY), is a rare inherited form of diabetes caused by a single gene mutation. It is distinct from both type 1 and type 2 diabetes and is often misdiagnosed as one of these more common types.
MODY typically presents in children, adolescents or young adults, usually before the age of 25, and often runs strongly in families across multiple generations.
Why does MODY occur?
MODY occurs due to a mutation in a single gene involved in insulin production or glucose regulation. This mutation is usually inherited in an autosomal dominant pattern, meaning there is a 50% chance of passing it on to offspring if one parent is affected.
To date, more than 14 different gene mutations have been identified, each causing a specific subtype of MODY. The most common forms include:
- HNF1A-MODY
- HNF4A-MODY
- GCK-MODY
Each subtype differs in severity, treatment requirements and long-term risk of complications.
How does MODY affect the body?
Like other forms of diabetes, MODY affects the body’s ability to regulate blood glucose.
Insulin is produced by the pancreas and allows glucose to enter cells to be used for energy. In MODY, insulin production may be reduced, delayed or improperly regulated, depending on the gene affected. This leads to elevated blood glucose levels and symptoms of diabetes.
Unlike type 1 diabetes:
- MODY is not autoimmune
- Ketosis is uncommon
- Insulin may not be required
Unlike type 2 diabetes:
- MODY is not caused by insulin resistance
- It often occurs in people who are not overweight
- Lifestyle factors are not the primary cause
Common features that may suggest MODY
MODY should be considered when:
- Diabetes is diagnosed at a young age (usually <25 years)
- There is diabetes across several generations
- There is no evidence of autoimmunity
- Insulin requirements are low or absent
- Blood glucose is mildly to moderately elevated and stable
- There is poor response or unexpected response to standard type 2 diabetes treatments
How is MODY diagnosed?
Diagnosis involves a combination of:
- Clinical assessment and family history
- Blood tests (including C-peptide and diabetes autoantibodies)
- Genetic testing, which confirms the diagnosis and identifies the specific MODY subtype
Accurate diagnosis is important, as it can significantly change treatment decisions and guide screening of family members.
Can MODY be prevented?
MODY cannot be prevented, as it is caused by a genetic mutation present from birth.
Can MODY be treated?
Yes. With accurate and timely diagnosis, MODY can be very effectively managed, and treatment varies depending on the subtype.
Management may include:
- No treatment at all (e.g. some forms such as GCK-MODY)
- Low-dose oral medications (such as sulfonylureas)
- Insulin therapy in selected cases
- Lifestyle optimisation and regular monitoring
Correct diagnosis often allows people to stop unnecessary insulin and switch to simpler, more appropriate treatment.
Specialist care for MODY
Because MODY is uncommon and frequently misdiagnosed, specialist endocrine assessment is essential. Identification of the correct subtype enables personalised treatment, improved long-term outcomes, and appropriate genetic counselling for family members.
Please ask your GP for a referral to Dr Imran to discuss assessment, genetic testing and tailored management of your condition.