2 - monogenic diabetes (& MODY)

Question 1

what is monogenic diabetes? what are the types?

Answer 1

it’s diabetes caused a mutation in a single gene (mendelian disease)

1. MODY
2. neonatal diabetes

Question 2

what is the key pathological feature of severe insulin resistance?

Answer 2

acanthosis nigricans = pigmented velvet like appearance of skin in axilla, skin folds, back of neck etc

(it’s when severe insulin resistance but body still making loads of insulin & this insulin only working on epithelial tissue causing epithelial overgrowth)

Question 3

what is MODY?

Answer 3

maturity onset diabetes of young (like type 2 diabetes in that it doesn’t need insulin treatment but in young people)

= it’s autosomal dominant inheritance of single gene mutation making beta cell dysfunction

Question 4

what is glucokinase MODY? presentation? management?

Answer 4

it’s a type of MODY where glucokinase mutation

glucokinase = rate limiting enzyme in glycolysis (1st step). it basically controls how insulin goes up as glucose goes up.

in glucokinase MODY fasting level is set at 7 (normally 5), means people just sit at higher natural glucose level (stable hyperglcyaemia)

they have no higher risk of complications and don’t need treatment

Question 5

what is transcription factor MODY? presentation? management?

Answer 5

it’s mutation in transcription factor, which is altering how mitochondria makes ATP

presents normal beta cell function at birth but gets worse over time so progressive hyperglycaemia
= presents as adolescent or young adult

• likely complications
• treat by managing diet, giving insulin and SU’s

Question 6

what specific mutation of transcription factor MODY is most sensitive to sulphonylureas?

Answer 6

HNF-1 alpha MODY (and HNF-1 beta)

• sulphonylureas are 4x more effective than in T2DM so they have low dose SU

Question 7

what test will be different for MODY and type 1 diabetes mellitus?

Answer 7

MODY will have normal c-peptide as pancreas still functioning but type 1 would have low c-peptide

Question 8

what is neonatal diabetes? what is treatment?

Answer 8

when genetic defect in potassium ATP channel- Kir6 (can’t close it) so can’t make insulin (no c-peptides made)

can treat with sulphonylureas cause they close K ATP channel so basically means person can just make their own insulin (very good! - no need for insulin therapy etc)

= high dose of SU