Week 4

Question 1

purpose of beta cells

Answer 1

produce store and release insulin in response to rising blood glucose

Question 2

how does glucsoe enter beta cell

Answer 2

Glut 2

Question 3

What occurs to glucose in beta cell

Answer 3

metabolised so ATP inceased binds to K channel so K no longer exits

Question 4

what occurs after ATP bnding to K channels in B cell

Answer 4

K channel shuts so K cant exit and cell depolarizes and calcium ions can now enter the cell leading to insulin release

Question 5

K channel structure

Answer 5

4SURI subunits and 2 Kir6.2 subunits

Question 6

Importance of mutations in K channels in B cells

Answer 6

prevent closing so break link between glucose levels and insulin release- neonatal as mutations in K channels in 40% of patients

Question 7

Characteristics of MODY

Answer 7

early diagnosis and seems to be type 1 but autosomally dominantly inherited not tyoe 1 characteristics and can take breaks from insulin

Question 8

What is MODY

Answer 8

maturity onset diabetes of the young

non insulin dependent- gene defect causes defect in beta cell function

Question 9

different types and frequencies

Answer 9

66% by trans factors 22% by glucokinase

Question 10

What does glucokinase MODY do

Answer 10

is pancreatic glucose sensor so setpoint higher- born with higher blood glucose

Question 11

best treatment for glucokinase MODY

Answer 11

do not treat as if give insulin body stops producing tis own and has no effect

Question 12

HNF1a and HNF4A mutation frequency and effect

Answer 12

61% and 4% of mody respectively
autosomal dominant
beta cell reduced function

Question 13

treatment of HNF1a MODY

Answer 13

respond 4 fold better to SU compared to T2D so low dose of SU better treatment than insulin

Question 14

Sulphonylurea effect

Answer 14

binds to K channel causing elss K to leave cell so more depol an more ca entering so more insulin release

Question 15

HNF1B MODY effect

Answer 15

recued number of beta cells as problems with pancreatic development- it is smaller

Question 16

HNF1B MODY treatment

Answer 16

Need insulin to treat, don’t respond to SU

Question 17

neonatal diabetes diagnosis

Answer 17

below 6 months caused by genetics

HLA analysis suggests type 1 diabetes very uncommon before 6 months

Question 18

Kir6.2 neonatal effect

Answer 18

ATP binding sites on K channel mutated so dont close

Question 19

Kir6.2 neonatal treatment

Answer 19

high dose SU- casues k clsoing

lowers glucose values and less fluctuation

Question 20

Kir6.2 mutation V59M

Answer 20

causes neurological problems

Developmental delays in 21% of Kir6.2

Question 21

Developmental delays in neonatal

Answer 21

5% DEND- developmental delay (severe), epilepsy, neonatal diabetes

16% intermediate DEND mild developmental delay no epilepsy nd neonatal diabetes

Question 22

Treatment of type 1 diabetes

Answer 22

Insulin

Question 23

treatment of type 2 diabetes

Answer 23

Metformin

Question 24

Importance of evaluation of tests

Answer 24

Measurement of what value of something new is relative to current precise- reveal new values

Question 25

ACCE wheel

Answer 25

Analytic validity Clinical validity Clinical utility Ethical legal and social implications

Question 26

Disorder and setting

Answer 26

essential background What is disorder what are clinical findigns,

Question 27

Analytical vailidity

Answer 27

Defines ability to accurately and reliably measure genotype of interest Sensitivity and specificity

Question 28

Clinical validity

Answer 28

Ability of a test to detect or predict the associate disorder Sensitivity, specificity, PPR and NPV

Question 29

Clinical utility

Answer 29

Defines the elements that need to be considered when evaluating risk and benefits with intro to routine practice Focuses on health outcomes positive and negative

Question 30

Ethical, legal and social implications

Answer 30

What is known about stigma, primary. Are there consent issues

Question 31

sensitivity calculation

Answer 31

true positive rate= TP/P

Question 32

specificity and calc

Answer 32

true negative rate= TN/N

Question 33

PPv

Answer 33

TP/TP+FP

Question 34

NPV

Answer 34

TN/Tn+FN

Question 35

predictive risk

Answer 35

Relative risk would be 1 if test was not beneficial | If positive then above 1

Question 36

The test’s ability to predict the occurrence of the adverse event of interest

Answer 36

Clinical Validity

Question 37

The probability of an adverse event when the genetic variant is present

Answer 37

PPV

Question 38

The probability of no adverse event when the genetic variant is absent

Answer 38

NPV

Question 39

Indicates potential benefit of a pharmacogenetic test (expected reduction in adverse events or number of patients requiring a different treatment)

Answer 39

Population impact

Question 40

measurement of population impact

Answer 40

Population attributable fraction

Question 41

The number of individuals who would need to be genotyped to prevent one patient having an adverse event

Answer 41

Number needed to gentype

Question 42

Required for the implementation of a pharmacogenetics test as a well as clinical validity and population impact evaluation

Answer 42

economic evaluation

Question 43

The ability of a test to discriminate between adverse events, measured by sensitivity and specificity

Answer 43

discriminative accuracy