MODY

Question 1

What is MODY and how does it differ from type 1 and type 2 diabetes?

Answer 1

MODY is a monogenic form of diabetes with autosomal dominant inheritance, usually presenting before age 25, caused by impaired insulin secretion without insulin resistance or autoimmune destruction.

Question 2

What inheritance pattern is classically seen in MODY?

Answer 2

Autosomal dominant inheritance, often affecting multiple generations.

Question 3

Approximately what proportion of people with diabetes have MODY?

Answer 3

Around 1–2% of patients with diabetes mellitus.

Question 4

Why is MODY frequently misdiagnosed?

Answer 4

Because it is often incorrectly classified as type 1 or type 2 diabetes, with around 90% of cases mislabelled.

Question 5

How many genetic subtypes of MODY have been identified?

Answer 5

More than 14 subtypes.

Question 6

Which MODY subtypes are the most common?

Answer 6

MODY3 (HNF1A mutation) and MODY2 (GCK mutation).

Question 7

What proportion of MODY cases are caused by MODY3 and MODY2 respectively?

Answer 7

MODY3 accounts for ~60% of cases and MODY2 for ~20%.

Question 8

Why is identifying the specific MODY subtype important?

Answer 8

Because management, prognosis, and genetic counselling differ significantly between subtypes.

Question 9

How do patients with MODY typically present?

Answer 9

With mild, non-ketotic hyperglycaemia, often discovered incidentally or on routine screening.

Question 10

How does MODY differ from type 1 diabetes at presentation?

Answer 10

Patients with MODY do not usually present with diabetic ketoacidosis and are not autoimmune.

Question 11

How does MODY differ from type 2 diabetes clinically?

Answer 11

Patients are often young, of normal weight, and lack features of insulin resistance.

Question 12

Is ketoacidosis common in MODY?

Answer 12

No, ketoacidosis is rare and usually only occurs during severe physiological stress.

Question 13

In what clinical situation is MODY often first detected?

Answer 13

During routine blood tests or pregnancy screening.

Question 14

What is the typical phenotype of MODY2 (GCK mutation)?

Answer 14

Mild, stable fasting hyperglycaemia with low risk of long-term complications.

Question 15

Does MODY2 usually require pharmacological treatment?

Answer 15

No, treatment is often unnecessary as complications are rare.

Question 16

What is characteristic of MODY3 (HNF1A mutation)?

Answer 16

Progressive hyperglycaemia with a higher risk of microvascular complications.

Question 17

Which MODY subtype responds particularly well to sulfonylureas?

Answer 17

MODY3 (HNF1A) and MODY1 (HNF4A).

Question 18

When should MODY be suspected clinically?

Answer 18

In patients diagnosed with diabetes before age 25 who are non-obese, lack insulin resistance, and have a strong family history.

Question 19

What is the definitive diagnostic test for MODY?

Answer 19

Genetic testing to identify the causative mutation.

Question 20

Why is genetic testing clinically valuable in MODY?

Answer 20

It guides treatment choice, prognosis, and family screening.

Question 21

How is MODY2 typically managed?

Answer 21

Usually no treatment is required due to mild, stable hyperglycaemia.

Question 22

What is first-line treatment for MODY caused by HNF1A mutations?

Answer 22

Low-dose sulfonylureas.

Question 23

When might insulin be required in MODY patients?

Answer 23

During pregnancy, severe hyperglycaemia, or when sulfonylureas are ineffective or contraindicated.

Question 24

What combination of features strongly suggests MODY rather than type 1 or type 2 diabetes?

Answer 24

Young age of onset, autosomal dominant family history, non-obese phenotype, absence of ketosis, and preserved insulin production.