MODY Flashcards
Describe MODY
Maturity-onset diabetes of the young has autosomal dominant inheritance and is a type of non-insulin dependent diabetes; people with MODY tend to be mistakenly diagnosed with another type of diabetes
It is a heterogeneous group of conditions with different types, due to different mutations, and a strong FH is typical
Age of onset usually before age 25
Types of MODY (based on where the mutation is)?
Glucokinase - in this type, there is abnormal glucose sensing but there is nothing else wrong
Transcription factors - problems begin in teen years and then progress:
• HNF1α (majority)
• HNF4α
• HNF1β
MODY-X
Also, MODY 4, 6, 7, 8
2 distinct phenotypes of MODY?
Normal blood glucose tends to increase from 4 to 6 mmol/L as children grow
In glucokinase MODY, this is the same but glucose increases from 7 to 9 mmol/L as they grow older (i.e: glucose is abnormally high from birth but nothing else is wrong)
In HNF1α MODY, the glucose levels increases exponentially from birth, i.e: it starts normal but increases to high levels by the age of 80
Describe treatment of glucokinase MODY
Tends to be found on incidental testing but there is no need for follow-up; patients do not require insulin, as this type does NOT cause complications
Principles of Glucokinase mutation MODY?
Onset AT BIRTH but there is stable hyperglycaemia; requires only diet treatment and complications are rare
Principles of transcription factor mutation in MODY?
Adolescence/young adult onset of progressive hyperglycaemia
Different people are controlled differently:
• Diet
• Oral hyperglycaemic agents
• Insulin
Complications are common
What is neonatal diabetes?
Rare type of genetic diabetes that requires insulin treatment within the first 3 months of life
Types of neonatal diabetes?
Transient neonatal diabetes (TNDM) - usually diagnosed <1 week old and resolves within 12 weeks (median); then, insulin can be stopped
Permanent neonatal diabetes (PNDM) - diabetes usually diagnosed within 0-6 weeks (T1DM DOES NOT occur at this age) of age; thought to require life-long insulin treatment but can be transferred to sulphonylureas
When does T1DM not occur?
Does not occur <6 months of age; previously, neonatal diabetes was often misdiagnosed as T1DM, as there are similar features, but it does not occur at this age
Pathophysiology of neonatal diabetes?
Mutation in the KATP channel, so ATP no longer closes it
Membrane is hyperpolarised and there is no calcium influx
NO INSULIN SECRETION
Main treatment option for PNDM?
Sulphonylureas, e.g: Glibenclamide
Mechanism of action of sulphonylureas in PNDM?
Close the KATP channel and the membrane is depolarised, allowing calcium influx
Insulin secretion occurs
