Key features of MODY Early onset:
Usually diagnosed before the age of 25.
Autosomal dominant inheritance:
Passed down from one parent, with a 50% chance of inheritance.
Non- autoimmune and non- insulin dependent:
In most cases, insulin is not initially required.
Variable severity:
Clinical presentation depends on the specific genetic mutation.
Types of MODY
There are 14 identified subtypes of MODY, each caused by a different gene mutation. The most common are:
1. MODY 1 (HNF4A Mutation):
Characteristics: Mild hyperglycaemia in childhood; significant post-meal glucose elevation.
Treatment: Often responds well to low-dose sulfonylureas.
2. MODY 2 (GCK Mutation):
Characteristics: Mild, stable fasting hyperglycaemia (100-140 mg/dL); rarely causes complications.
Treatment: Typically no treatment is required, as long as blood sugar levels remain stable.
MODY 3 (HNF1A Mutation):
Characteristics: Progressive hyperglycemia with significant post-meal spikes; increased risk of complications.
Treatment: Excellent response to sulfonylureas, often better than insulin.
4. MODY 5 (HNF1B Mutation):
Characteristics: Associated with kidney abnormalities, genital malformations, and other systemic issues.
Treatment: Insulin therapy is often required.
Treatment of MODY
1. MODY-specific treatments:
MODY 1 & 3: Oral sulfonylureas (e.g., glipizide, gliclazide) are highly effective.
MODY 2: Lifestyle modifications; pharmacological treatment is rarely needed.
MODY 5: May require insulin and management of associated kidney or systemic complications.
2. General Diabetes Management:
Diet and Exercise: Maintain a healthy diet and regular physical activity.
■Monitoring: Regular glucose checks and monitoring for complications.
Complications of MODY
■MODY 2: Minimal complications.
MODY 1, 3, and 5: Risk of long-term complications (e.g.. kidney disease, cardiovascular disease) if not well-managed.
MODY 5: Additional risks due to kidney and urogenital abnormalities.
Why is MODY diagnosis important?
Helps avoid unnecessary insulin therapy in patients who respond well to oral medications.
Enables targeted treatment based on the specific MODY subtype.
Allows for genetic counseling of family members, as the condition is inherited.
Diagnosis of MODY
MODY is often misdiagnosed as type 1 or type 2 diabetes. Diagnosis involves:-
1. Clinical features:
Diabetes onset before 25 years.
Family history of diabetes in multiple generations.
Absence of obesity or signs of insulin resistance (in most cases).
2. Laboratory tests:
C-Peptide levels: Normal or slightly reduced, unlike in type 1 diabetes where levels are very low.
Autoantibodies: Negative for autoimmune markers (e.g., GAD65, islet cell antibodies).
3. Genetic testing:
Confirms the specific gene mutation responsible for MODY.
Recommended for patients with a strong family history of diabetes and atypical features for type 1 or type 2 diabetes.
