Monogenic Diabetes

Question 1

what is monogenic diabetes

Answer 1

diabetes caused by a mutation in a single gene

Question 2

what is the most common type of monogenic diabetes

Answer 2

MODY(Maturity Onset Diabetes of the Young)

Question 3

how can monogenic diabetes affect insulin physiology

Answer 3

can result in defect in insulin secretion or insulin sensitivity

Question 4

what types of monogenic diabetes involve defects in insulin secretion

Answer 4

MODY, Neonatal diabetes

Question 5

how many different genes are linked to MODY and neonatal diabetes

Answer 5

MODY = ~11 genes
Neonatal = 35 genes

Question 6

how many different genes are linked to defects in insulin action

Answer 6

9 genes(such as AKT or CIDEC)

Question 7

what different aspects of insulin action can defects arise in monogenic forms of diabetes

Answer 7

defects in insulin signalling pathway(eh AKT) or defect in fat storage(eg CIDEC)

Question 8

what symptom can be seen with insulin resistance and particularly monogenic forms of insulin resistance
(ie in hyperinsulinaemic states)

Answer 8

acanthosis nigricans, pigmentation of skin in armpits/flexial creases of skin, when insulin is too high and acts on skin to drive epithelial growth

Question 9

what is lipodystrophy, seen in monogenic diabetes resulting in defects of fat storage

Answer 9

dystrophic fat formation, can be different patterns and affect different parts of body

Question 10

what is a difference and a similarity in MODY and T1DM

Answer 10

different = MODY is non-insulin dependant 
same = usually early onset, <25y/o

Question 11

what pattern of inheritance is seen in MODY

Answer 11

autosomal dominant

Question 12

what are the 3 broad different forms of MODY

Answer 12

defects in glucokinase(14%), defects in transcription factors(75%), MODY x

Question 13

what is MODY x

Answer 13

undefined group with unknown cause but with all characteristics of MODY

Question 14

what is the role of glucokinase in glucose metabolism in the pancreatic beta cell

Answer 14

converts glucose to glucose-6-phosphaet, first step in glycolysis

Question 15

when is the onset of glucokinase MODY compared to transcription factor mutation and neonatal MODY

Answer 15

glucokinase = from birth
transcription factor = from adolescents/young adult
neonatal = in first 6 months of life

Question 16

describe the hyperglycaemia seen in glucokinase MODY compared to transcription factor mutation MODY

Answer 16

glucokinase = stable hyperglycaemia

transcription factor = progressive hyperglycaemia

Question 17

describe the fasting glucose of someone with glucokinase MODY and how they respond to glucose in blood

Answer 17

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

Question 18

describe the levels of diabetic complications seen in glucokinase compared to transcription factor MODY

Answer 18

glucokinase = complications rare

transcription factor = complications frequent

Question 19

what effect does insulin and other diabetes medication have on glucokinase MODY

Answer 19

has no impact, makes no difference to HbA1c levels

Question 20

why is there not a need to try and treat those with glucokinase MODY to lower blood glucose

Answer 20

because it is not associated with any increased risk of diabetic complications

Question 21

what is the most common form of transcription factor MODY

Answer 21

HNF1A MODY

Question 22

what type of diabetes drugs are particularly sensitive in HNF1A MODY

Answer 22

low dose sulphonylureas(eg Gliclazide), ~4 times more sensitive these patients than those with T2DM
(if on insulin prior transition off it)

Question 23

what 2 genes are responsible for majority(50%) of Neonatal diabetes, and what defect do they cause

Answer 23

KCNJ11 and ABCC8

affect Katp channel in beta cells, mean they do not close in response to ATP

Question 24

what type of diabetes drug can be used to treat neonatal diabetes and lower blood glucose

Answer 24

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)