From the Guidelines
MODY (Maturity-Onset Diabetes of the Young) is a rare form of diabetes caused by a single gene mutation that affects insulin production, and the most recent guidelines from 2022 recommend considering MODY in patients with mild stable fasting hyperglycemia and multiple family members with diabetes that is not typical of T1DM or T2DM 1.
Key Features of MODY
- Inherited in an autosomal dominant pattern, meaning a child has a 50% chance of inheriting it if one parent has the mutation
- Several subtypes, with the most common being HNF1A (MODY 3), GCK (MODY 2), and HNF4A (MODY 1)
- Treatment varies by subtype - patients with HNF1A or HNF4A MODY often respond well to low-dose sulfonylureas like gliclazide (40-80mg daily) rather than insulin
- GCK MODY typically doesn't require treatment as blood glucose levels remain stable
Diagnosis and Genetic Testing
- Diagnosis requires genetic testing, which is important because MODY is often misdiagnosed as type 1 or type 2 diabetes
- Key features suggesting MODY include diabetes diagnosis before age 25, strong family history across multiple generations, absence of autoantibodies, and preserved insulin production
- Proper diagnosis is crucial as it leads to more appropriate treatment, better glucose control, and proper genetic counseling for family members who may also carry the mutation
Recommendations
- Patients with suspected MODY should be referred to a specialist for further evaluation if available, and consultation is recommended 1
- Genetic testing 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
From the Research
Definition and Characteristics of Maturity-Onset Diabetes of the Young (MODY)
- Maturity-onset diabetes of the young (MODY) is a non-insulin-dependent form of diabetes mellitus that is usually diagnosed in young adulthood 2.
- MODY is most often an autosomal dominant disease and is divided into subtypes (MODY1 to MODY14) based on the causative genetic mutation.
- Subtypes 1 to 3 account for 95% of cases.
Diagnosis and Misdiagnosis of MODY
- MODY is often misdiagnosed as type 1 or 2 diabetes and should be suspected in nonobese patients who have diabetes that was diagnosed at a young age (younger than 30 years) and a strong family history of diabetes 2.
- Patients with MODY have preserved pancreatic beta-cell function three to five years after diagnosis, as evidenced by detectable serum C-peptide levels with a serum glucose level greater than 144 mg per dL and no laboratory evidence of pancreatic beta-cell autoimmunity.
Treatment Options for MODY
- Lifestyle modification including a low-carbohydrate diet should be the first-line treatment for MODY1 and MODY3 2.
- Sulfonylureas are the preferred pharmacologic therapy based on pathophysiologic reasoning, although clinical trials are lacking 2, 3.
- Patients with MODY2 have mild stable fasting hyperglycemia with low risk of diabetes-related complications and generally do not require treatment, except in pregnancy 2.
- Newer blood glucose-lowering therapies, such as SGLT2 inhibitors (SGLT2i), DPP-4 inhibitors (DPP4i) and GLP-1 receptor agonists (GLP-1RA), have a much lower risk of hypoglycaemia and usually have a favourable effect on body weight 4, 5.
- SGLT2 inhibitors may be an effective and potent treatment option in addition to sulfonylureas for individuals with MODY3 5.
Management of MODY During Pregnancy
- Pregnant patients with MODY may require insulin therapy and additional fetal monitoring for macrosomia 2.
- Proper management guidelines during pregnancy have been developed for carriers of GCK gene mutations, but such guidelines are still a subject of debate in other cases, although some recommendations are available 6.