Monogenic Diabetes Flashcards
what is monogenic diabetes
diabetes caused by a mutation in a single gene
what is the most common type of monogenic diabetes
MODY(Maturity Onset Diabetes of the Young)
how can monogenic diabetes affect insulin physiology
can result in defect in insulin secretion or insulin sensitivity
what types of monogenic diabetes involve defects in insulin secretion
MODY, Neonatal diabetes
how many different genes are linked to MODY and neonatal diabetes
MODY = ~11 genes Neonatal = 35 genes
how many different genes are linked to defects in insulin action
9 genes(such as AKT or CIDEC)
what different aspects of insulin action can defects arise in monogenic forms of diabetes
defects in insulin signalling pathway(eh AKT) or defect in fat storage(eg CIDEC)
what symptom can be seen with insulin resistance and particularly monogenic forms of insulin resistance
(ie in hyperinsulinaemic states)
acanthosis nigricans, pigmentation of skin in armpits/flexial creases of skin, when insulin is too high and acts on skin to drive epithelial growth
what is lipodystrophy, seen in monogenic diabetes resulting in defects of fat storage
dystrophic fat formation, can be different patterns and affect different parts of body
what is a difference and a similarity in MODY and T1DM
different = MODY is non-insulin dependant same = usually early onset, <25y/o
what pattern of inheritance is seen in MODY
autosomal dominant
what are the 3 broad different forms of MODY
defects in glucokinase(14%), defects in transcription factors(75%), MODY x
what is MODY x
undefined group with unknown cause but with all characteristics of MODY
what is the role of glucokinase in glucose metabolism in the pancreatic beta cell
converts glucose to glucose-6-phosphaet, first step in glycolysis
when is the onset of glucokinase MODY compared to transcription factor mutation and neonatal MODY
glucokinase = from birth
transcription factor = from adolescents/young adult
neonatal = in first 6 months of life
describe the hyperglycaemia seen in glucokinase MODY compared to transcription factor mutation MODY
glucokinase = stable hyperglycaemia
transcription factor = progressive hyperglycaemia
describe the fasting glucose of someone with glucokinase MODY and how they respond to glucose in blood
high fasting glucose(usually around 7 at birth) and increases at same rate as normal with age
respond well to increase blood glucose, no other issues with beta cells
describe the levels of diabetic complications seen in glucokinase compared to transcription factor MODY
glucokinase = complications rare
transcription factor = complications frequent
what effect does insulin and other diabetes medication have on glucokinase MODY
has no impact, makes no difference to HbA1c levels
why is there not a need to try and treat those with glucokinase MODY to lower blood glucose
because it is not associated with any increased risk of diabetic complications
what is the most common form of transcription factor MODY
HNF1A MODY
what type of diabetes drugs are particularly sensitive in HNF1A MODY
low dose sulphonylureas(eg Gliclazide), ~4 times more sensitive these patients than those with T2DM
(if on insulin prior transition off it)
what 2 genes are responsible for majority(50%) of Neonatal diabetes, and what defect do they cause
KCNJ11 and ABCC8
affect Katp channel in beta cells, mean they do not close in response to ATP
what type of diabetes drug can be used to treat neonatal diabetes and lower blood glucose
high dose sulphonylureas(eg Glibenclamide), SUs act to close the Katp channel which remains open in majority of neonatal MODYs
(if on insulin prior can transition off it)
