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
A 35-year-old man, diagnosed as having type 2 diabetes mellitus 10 years ago, has had poor control despite taking metformin. Several family members also have diabetes mellitus and a recent genotyping revealed a mutation in the HNF -1 alpha.
What is the most appropriate treatment?
Sulfonylureas
What is the most common subtype of Maturity Onset Diabetes of the Young (MODY), and what gene is affected?
MODY 3 is the most common, caused by a mutation in the HNF1A gene
Which MODY subtype typically presents with mild hyperglycaemia (rarely above 7–8 mmol/L) and often responds to diet alone?
MODY 2, due to a glucokinase mutation
Which MODY subtype is linked to renal cysts, pancreatic atrophy, genital tract anomalies, and abnormal LFTs?
MODY 5, caused by HNF1B mutation
Which MODY subtype is highly sensitive to sulphonylureas and may require insulin if there’s no response?
MODY 3 (HNF1A mutation)
What gene is mutated in MODY 1, and how does it affect insulin secretion?
MODY 1 involves an HNF4A mutation and leads to reduced insulin secretion in response to glucose
= it also responds to sulphonylureas
