Monogenic forms of diabetes Flashcards
MODY
i) what is it?
ii) is it insulin dependent?
iii) what is inheritance pattern? where is the defect?
i) maturity onset diabetes in the young - like T2DM (dont need insulin) but onset is young <25yrs
ii) no insulin dependent
iii) auto dominant - caused by a single gene defect
- defect in beta cell function
MONOGENIC DIABETES
i) what are the two main groups?
i) neonatal diabetes (dx <6m age) and MODY (dx <25yrs age)
- neonatal is 1 in 100,000 births
- MODY is 2% of all diabetes
GLUCOKINASE MODY
i) what is glucokinase? what does it act as the rate limiting step in?
ii) what does a defect in the glucokinase gene cause?
iii) what glucose levels are seen?
iv) name two clinical features? are complications common or rare?
v) is treatment needed? at what time does the condition need to be managed
i) enzyme responsible for phosphorylation of glucose
- RLS in glucose release
ii) higher glucose levels
iii) family history, fasting glucose is controlled but higher than controls
- HbA1c is higher than those non affected family members (38-60)
iv) may be asymptomatic or lifelong mild stable fasting hyperglycaemia (HbA1c 30-60mmol/l)
- complications are rare
v) treatment is not necessary and ineffective
- need active management in pregnancy
PREGNANCY AND GLUCOKINASE MODY
i) is the baby birthweight affected if they inherit the GCK gene from mum?
ii) what is the treatment if the baby inherits the mutation?
iii) what is the treatment if the baby doesnt inherit the mutation
iv) how is the mutation tested for in the baby? (2)
v) what is prevalence of GC MODY?
i) normal birth weight
- if they didnt inherit the mutation then birth weight is higher (mums glucose is too high for baby)
ii) dont need any treatment as baby can deal with the hyperglycaemia
iii) baby will be bigger
- consider insulin to prevent macrosomia (doesnt usually work)
- delivery at 38/40wks
iv) CVS or amniocentesis or cfDNA testing
v) 1.1 in 1000 (2.5% of gestational diabetes cases)
HNF1A/4A MODY
i) what is the inheritance pattern?
ii) when is onset?
iii) which drugs do they respond well to?
iv) are these patients insulin dependent? are they usually obese?
v) what is additionally seen in 1A? 4A?
i) auto dominant
ii) younger onset (<25yrs) but can come on later in life (can be mistaken for T2DM)
iii) sulphonyureas (gliclizaide) and diet change
iv) not insulin dependent and not obese
v) 1A - low renal threshold for glucose and young onset CV disease
4a - macrosomia (higher birth weight) and neonatal hypoglycaemia (transient)
- babies with gene from mum > even bigger babies
HNF4A MODY
i) what glucose levels are seen in babies? when may they be delivered?
ii) what drug are they very responsive to?
iii) what do patient progress to in early adulthood? (2)
iv) name three clues that there may be a HNF4A mutation
i) neonatal hypoglycaemia (too much insulin in utero and defect in insulin production later)
- deliver before 37 weeks to mitigate high birth weight risk
ii) SUs - gliclazide
iii) progress to beta cell failure and diabetes in early adulthood
iv) history of macrosomia, history of neonate hypogly, more than two generation history of diabetes
NEONATAL DIABETES
i) what is it? what % are transient? what do they rest respond better to?
ii) where are the mutations that cause permanent type?
iii) which medication works best?
i) all diabetes diagnosed <6 months of age
- 50% are transient
- persistent - respond better to tablets than insulin
ii) mutation in the potassium channel of beta cells (SUs work on the K+ channel)
- k+ channels ABCC8 and KCNJ11
iii) high dose oral medication (sulphonylureas eg glibenclamide)
SUMMARY
i) what three symptoms may be seen in GCK? what BMI do most people have
ii) what is seen in HNF1A?
iii) what two extra things are characteristic of HNF4A
iv) what is the best treatment for neonatal diabetes
i) asymptomatic, fasting hypergluy and high insulin in pregnancy
- normal BMI
ii) family history of diabetes, young onset and non insulin dep babies
iii) macrosomia and neonatal hypogly
iv) high dose SU
