Week 4 Flashcards
What do beta cells do?
Produce store and release insulin
Insulin
Secreted due to rising blood sugar level and promotes the uptake of glucose in cell, specifically live muscle and adipose tissues
Insulin secretion pathway
- Glucose enters beta cell through GLUT2 transporter.
- Metabolised glucose increases ATP.
- ATP bind to K+ channels causing closure.
- Stoping the movement of K+ out of the cell.
- Cell membrane depolarises.
- Voltage dependent potassium channels open.
- Calcium ions enter the cell, leading to cascade of events.
- Consequently releasing insulin.
What is the potassium channel made up of in the beta cell?
SURI subunit which is the product of the ABCC8 gene and KIR6.2 subunit which is the product of the KCNJ11 gene.
What is the cause of neonatal diabetes 40% of the time?
Mutation is the potassium channel genes.
What is the treatment for when you have a mutation in the potassium channels and when and how would this be tested for?
Sulphonylurea tablets
Neonatal diabetes as 40% of the cases of neonatal diabetes are caused by this mutation.
This would be tested for with genetic testing.
How does the treatment for mutated potassium channels work?
Sulphonylurea acts by binding to the K+ channels and closing it independently from ATP, this allows the pathway to carry on, so that insulin can be released.
What is Glucokinase function in the body?
It is the sensor for glucose on the beta cell.
What occurs if there is a glucokinase mutation?
It will have a low sensitivity to glucose before insulin is released, causing a high blood glucose.
What is the treatment for MODY when there is a mutation in the Glucokinase?
There is no treatment and it causes no damage to the kidneys or eyes. injecting insulin would only cause your beta-cells to stop releasing insulin which is counterproductive.
What happens if you have HNF1B-MODY?
It effects early pancreatic development, meaning patients would have a small pancreas, so the treatment would be insulin as subsequent amounts cannot be produced.
When is neonatal diabetes tested for?
When an infant under 6months old is showing signs of diabetes, because it would be too early to have an autoimmune disease.
Evaluation
Merely the measurement of what the value of doing something(often new) is,
This is generally compared to the current practise.
What is the ACCE wheel?
It shows the Clinical utility and Ethical, legal and social implications. Within that it shows the Analytical validity, Clinical validity, and social implications
What is Analytical validity?
Defines the ability to accurately and reliably measure the genotype of interest.
What is the Clinical validity?
extent to which a test result is predictive for disease
- sensitivity and specificity
What is sensitivity?
How often is the test positive when the disorder is present?
What is specificity?
How often is the test negative when a disorder is not present?
How does Prevalence relate to clinical validity?
How common is the disorder in this setting?
Clinical Utility of a genetic test?
Defines the elements that need to be considered when evaluating the associated risks and benefits
Test Purpose - Legitimacy
Conform to social preferences
Test Purpose - Efficacy
Potential of test and associated services to deliver health benefit
Test Purpose - Effectiveness
Actual delivery of health benefit in routine clinical setting
Test Purpose - Appropriateness
Expected health benefit exceeds expected negative consequences by a sufficient wide margin that the test is worth doing
Feasibility of test delivery - Acceptability
Conformity to the wishes, desires, and expectations of patients and their families.
Feasibility of test delivery - Efficiency
Ability to lower the costs of care without diminishing benefits
Feasibility of test delivery - Optimality
Balancing improvements in health against cost of improvement
Feasibility of test delivery - Equity
Just and fair distribution of health care and its benefits among members of the population
What is QALY?
Quality adjusted life year
What is ICER?
Incremental cost effectiveness ratio
- Relative to current practice
Change in cost/change in effect
What patients would have characteristics of MODY?
They would not have the specific antibodies from type 1 diabetes and C-peptide- which would decide if you then had next generation sequencing.
What are three economic modelling techniques?
Decision analytic modelling
Markov modelling
Discrete even simulation
For a mendelian disorder, what is the positive predicted value?
Penetrance
