Monogenic diabetes

Monogenic diabetes (also known as maturity onset diabetes of youth [MODY]) accounts for 4 to 6% of cases of diabetes in children and adolescents. It is caused by a single gene defect in pancreatic beta-cell function and is usually autosomal dominant in transmission. Some adults with monogenic diabetes may have been misclassified as having type 1 or type 2 diabetes when first diagnosed.

Suspect a monogenic form of diabetes when:

• there is a strong family history of diabetes in patients who are not obese
• there is a young age of onset (classically before 25 years, although a diagnosis may occur at an older age)
• the patient is negative for type 1 diabetes–associated autoantibodies
• a low dose of insulin optimises the glycaemic profile.

Risk of MODY for a patient can be further assessed using an online tool ¹. Seek specialist involvement for diagnosis and management of monogenic diabetes, which may include genetic counselling.

The commonest forms of monogenic diabetes are due to mutations in the HNF-1alpha and GCK genes. HNF-1alpha and the less common HNF-4alpha gene mutations are associated with progressive beta-cell dysfunction. They are associated with a long-term risk of microvascular complications. Monogenic diabetes due to HNF-1alpha and HNF-4alpha gene mutations may respond to a very low dose of sulfonylurea, but insulin is often eventually needed.

GCK gene mutations raise the set point of glucose detection for insulin release; these patients have lifelong asymptomatic elevated fasting blood glucose concentrations. Treatment is usually not required; however, women who become pregnant require specialist assessment and management.

Diagnosis of diabetes before 6 months of age is unusual and is suggestive of permanent neonatal diabetes, a rare form of monogenic diabetes often caused by genetic mutations encoding the KCNJ11 or ABCC8 genes.

There are also other rarer causes of monogenic diabetes and treatment can differ between the different forms. Specialised assessment and management are required for these rare conditions.