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 evidence suggests that patients with HNF1A or HNF4A MODY often respond well to low-dose sulfonylureas, while GCK MODY typically doesn't require treatment, as stated in the 2024 study 1.
Key Features of MODY
- Inherited in an autosomal dominant pattern, meaning a child has a 50% chance of developing 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, with patients with HNF1A or HNF4A MODY often responding well to low-dose sulfonylureas like gliclazide (40-80mg daily) rather than insulin, as supported by the 2024 study 1
- GCK MODY typically doesn't require treatment as blood glucose levels remain stable
Diagnosis and 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, as noted in the 2020 study 1
- Proper diagnosis ensures appropriate treatment, as many MODY patients can avoid insulin injections and maintain good glucose control with oral medications or sometimes no medication at all, as highlighted in the 2023 study 1
Clinical Implications
- The treatment implications for MODY are considerable and warrant genetic testing, as stated in the 2024 study 1
- Patients with HNF1A or HNF4A MODY usually respond well to low doses of sulfonylureas, which are considered first-line therapy
- Mutations or deletions in HNF1B are associated with renal cysts and uterine malformations (renal cysts and diabetes [RCAD] syndrome), as reported in the 2020 study 1
- Other extremely rare forms of MODY have been reported to involve other transcription factor genes, including PDX1 (IPF1) and NEUROD1, as mentioned in the 2018 study 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, with MODY2 being caused by mutations in the GCK gene, and MODY1 and MODY3 being caused by mutations in the HNF4A and HNF1A genes, respectively 2, 3.
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 2.
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 for MODY1 and MODY3 based on pathophysiologic reasoning, although clinical trials are lacking 2.
- Glucagon-like peptide-1 (GLP-1) receptor agonists have been shown to be effective in patients with MODY3, with advantages including a low risk of hypoglycemia and maintained β-cell function 4, 5.
- Patients with MODY2 generally do not require treatment, except in pregnancy, due to mild stable fasting hyperglycemia with low risk of diabetes-related complications 2.
- Newer blood glucose-lowering therapies, such as SGLT2 inhibitors, DPP-4 inhibitors, and GLP-1 receptor agonists, may be effective in MODY patients, with a lower risk of hypoglycemia and favorable effects on body weight 6.