MODY Flashcards
What is MODY?
Maturity-Onset Diabetes of the Young (MODY) is an
(1) early-onset
(2) non-insulin-dependent diabetes
(3) caused by a single gene mutation
(4) affecting β-cell function
What is the inheritance pattern of MODY?
autosomal dominant
What are the most common gene mutations in MODY?
- GCK MODY
= Glucokinase mutation - HNF1A MODY
= Hepatocyte nuclear factor 1-alpha mutation - KCNJ11/ABCC8 mutations
= Neonatal diabetes mellitus - NDM
Which type of diabetes is MODY classified under?
monogenic diabetes
What is the main defect in glucokinase MODY?
Glucokinase activity is impaired, leading to a higher glucose threshold for insulin secretion. This results in stable hyperglycaemia from birth but without complications
What is the most common type of mutation in MODY?
Transcription factor mutations
What are the three major types of MODY mutations?
Glucokinase mutations (14%)
Transcription factor mutations (75%)
MODY X (unknown gene, 11%)
How is MODY due to glucokinase mutation typically present?
Onset at birth with stable hyperglycaemia that does not require treatment
How is MODY due to transcription factor mutations typically present?
Adolescent or young adult onset with progressive hyperglycaemia, requiring treatment
How can MODY be distinguished using an oral glucose tolerance test (OGTT)?
- Glucokinase mutation
= High fasting blood glucose (~7 mmol/L) but good response to oral glucose challenge. - Transcription factor mutation
= Normal fasting blood glucose but poor response to glucose challenge
What is the definitive test to diagnose MODY?
Genetic screening
How is glucokinase MODY managed?
Diet
How is MODY managed due to transcription factor mutations?
Diet + sulphonylureas or insulin
Patients are highly responsive to low-dose sulphonylureas and can be switched from insulin if misdiagnosed as type 1 diabetes
