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 treatment depends on the specific subtype, with patients with GCK-MODY often not requiring medication, while those with HNF1A or HNF4A typically respond well to low-dose sulfonylureas 1. MODY is inherited in an autosomal dominant pattern, meaning a child has a 50% chance of inheriting it if one parent has the mutation. There are several subtypes of MODY, with the most common being HNF1A (MODY 3), GCK (MODY 2), and HNF4A (MODY 1).
- Key characteristics of MODY include:
- Diagnosis before age 25
- Family history across multiple generations
- Absence of autoantibodies
- Preserved insulin production
- Treatment approach:
- Patients with GCK-MODY: no medication required, as they maintain stable blood glucose levels
- Patients with HNF1A or HNF4A: low-dose sulfonylureas, such as gliclazide, are considered first-line therapy
- Diagnosis requires genetic testing, which is important for proper treatment selection and family screening, as noted in the most recent guidelines 1. MODY is often misdiagnosed as type 1 or type 2 diabetes, but proper diagnosis can significantly impact treatment approach and prognosis, highlighting the importance of considering MODY in the differential diagnosis of young patients with diabetes 1.
From the Research
Definition and Characteristics of Diabetes Type 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 2.
- Subtypes 1 to 3 account for 95% of cases, with MODY1 and MODY3 having progressive hyperglycemia and vascular complication rates similar to patients with types 1 and 2 diabetes 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 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, DPP-4 inhibitors, and GLP-1 receptor agonists, have a much lower risk of hypoglycaemia and usually have a favourable effect on body weight 4, 5.
- The management of MODY3 should be flexibly individualized for each family member to ensure long-term adherence and appropriate glycemic control 3.