Monogenic Diabetes

Question 1

Monogenic Diabetes

Answer 1

• Diabetes caused by a mutation in a single gene
• Mendelian disease
• Autosomal dominant or recessive
• Result in defects in insulin secretion or insulin action

Question 2

Most common monogenic diabetes is called—-

Answer 2

MODY

Question 3

Tyoes of monogenic diabetes?

Answer 3

1. Defects in insulin secretion
   -MODY – Maturity Onset Diabetes of the Young
   ~11 genes identified as causal (not a single gene causes it)
   -Neonatal Diabetes (affects the babies soon after birth)
   Many genes – 35 - can explain up to 82% of Neonatal diabetes
2. Defects in insulin action
   9 genes – defects in insulin signalling pathway (e.g. AKT, INSR) or fat storage (e.g. CIDEC)

Question 4

What is the marker of severe monogenic IR?

Answer 4

Acanthosis nigricans – seen in hyperinsulinemic states (Severe IR) = Insulin driven epithelial overgrowth
This is due to epithelium of the skin is not resistance to insulin, you would get skin tags on the skin as insulin acts like growth factor

Question 5

Acanthosis nigricans is a monogenic example of defects in insulin signalling. T/F

Answer 5

T

Question 6

What is an example of monogeni IR that causes defects in fat storage?

Answer 6

CGL (Congenital Global Lipodystrophy) due to AGPAT2 mutation

Question 7

What is MODY?

Answer 7

• Autosomal Dominant inheritance (50% chance to the kids)
• Non-insulin dependent diabetes
• Age of onset usually before 25
• This is not T1 or T2

Question 8

two main types of MODY?

Answer 8

Question 9

GCK-MODY does not need insulin treatment or associated risks. Why not?

Answer 9

These ppl can manage the sugar level right and no retinopathy, these ppl doesn’t have diabetes symptoms but they still have diabetes.
You wont know about it until you get tested.

Question 10

What is the unique thing about HNF1A MODY?

Answer 10

• They have more sensitivity to Sulphonylurea than M and patients with T2DM
• This means they all can come off using insulin
• C-peptide checks to make sure pancreas is working properly.

Question 11

KCNJ11/ABCC8 NDM is a genetic disorder that….

Answer 11

…..they don’t produce C-peptide; i.e. not a good pancreas.
* it is related to neonatal diabetes
* No need insulin as Sulphonylureas bypass the genetic defect in the channel

Question 12

What is monogenic diabetes?

Answer 12

Diabetes caused by single gene defects. Usually autosomal dominant affecting beta-cell function. Common type is called MODY.
Rarely causes defects in insulin action

Question 13

Targeted treatment for GCK MODY?

Answer 13

No treatment required. No follow up required.

Question 14

Targeted treatment for HNF1A MODY?

Answer 14

Can transition off insulin onto low dose sulphonylureas

Question 15

Targeted treatment for KCNJ11/ABCC8 NDM ?

Answer 15

Can transition off insulin onto high dose sulphonylureas