LT1 Intro & Prevention vs Cure

Question 1

What is pharmacodynamics?

Answer 1

Drug action on biology = how the drug produces its therapeutic effect

What a drug does to the body

The study of the biochemical, physiologic, and molecular effects of drugs on the body

Question 2

What is pharmacokinetics?

Answer 2

The study of how the body interacts with administered substances for the entire duration of exposure

What the body does to a drug, refers to the movement of drug into, through, and out of the body

Question 3

What is pharmacogenomics?

Answer 3

The study of how a person’s genes affect how they respond to drugs

Question 4

What is metabolic disease?

Answer 4

Disease or disorder that dirupts normal metabolism

Problems with ntrient transport, nutrient digestion and build of toxic agents can occur

Question 5

What is metabolic syndrome?

Answer 5

Combination of risk factors = diabetes, high blood pressure and obesity

Putting a person at higher risk of CVD or T2D

Question 6

Define metabolism

Answer 6

Process of converting food to energy on a cellular level

Question 7

What is non-alcoholic fatty liver disease?

Answer 7

Non-alcoholic fatty liver disease (NAFLD) is caused by a buildup of fat in the liver, which prevents it from functioning properly

It’s often linked to being overweight or obese, but other factors can also contribute

Question 8

Why are T2D numbers inaccurate?

Answer 8

Because there are about 0.5million people undiagnosed with T2D

Question 9

What is the correlation between obesity and diabetes?

Answer 9

T1D is NOT associated with being overweight/obesity

T2D is CLOSELY assocaited with being overweight/obesity

Question 10

What occurs in early-stage non-alcoholic fatty liver disease?

Answer 10

Early stage NAFLD doesn’t usually cause harm
BUT

Associated with T2D, high blood pressure and kidney failure

All linked to obesity related metabolic dysfunction

Question 11

What are the stages of non-alcoholic fatty liver disease?

Answer 11

Early-stage NAFLD

NASH (non-alcoholic steatohepatitis)

Fibrosis = irreversible hardening of liver

Cirrhosis

Question 12

What is cirrhosis of the liver?

Answer 12

A chronic liver disease that occurs when healthy liver tissue is replaced by scar tissue. This prevents the liver from functioning properly

Question 13

What is diabetes mellitus diagnosis based on?

Answer 13

Solely on blood glucose concentration

Hyperglycaemia is abover 7mM fasting blood glucose

Euglycemia is 5mM fasting blood glucose

Question 14

How does the oral glucose tolerance test work?

Answer 14

Measure 2h after 75g glucose load

If glucose levels are abover 11.1 then diabetic

Question 15

What is the most accurate test for diabetes and why?

Answer 15

HbA1c test

Look at glycated Hb is a more accurate long term measure of glucose control compared to fasting glucose

Because fasting can be inaccurate if people do it incorrectly

Question 16

What blood glucose concentration counts as pre-diabetic?

Answer 16

Between 6mM - 7mM fasting blood glucose levels

Question 17

What counts as hypoglycaemic levels?

Answer 17

Below 4mM of fasting blood glucose levels

Question 18

Why is glucosuria dangerous?

Answer 18

High glucose in urine promotes large osmotic diuresis = a condition where the body produces more urine than normal

This can lead to dehyration, circulatory failure, brain damage and renal & heart failure

Question 19

Why is high blood glucose dangerous?

Answer 19

Because it promotes glycation of blood proteins = causing dysfunction

This can give indicaiton of duration of hyperglycaemia

Question 20

How does diabetes cause macro/microvascular damage?

Answer 20

High glucose levels react with proteins in the blood vessels, forming AGEs which can damage the endothelial lining and contribute to inflammation and vascular stiffness

Advanced Glycation End Products (AGEs)

Question 21

What does macrovascular blood vessel disease cause compared to microvascular?

Answer 21

Macrovascular = atherosclerosis and platelet aggregation and hypercoagulability

Leads to CHD, vascular disease

Microvascular = specific to diabetes and genetic factors appear to contirbute

Leads to nephropathy, retinopathy, and neuropathy

Question 22

How is T1D autoimmune disease triggered?

Answer 22

The exact cause of T1D is unknown, but it’s thought to be triggered by a combination of genetics and environmental factors.

The process is characterized by the activation of autoreactive T cells that attack the beta cells in the pancreas

Question 23

What other causes of diabetes are there except for T1D and T2D?

Answer 23

Genetic defects in beta-cell function = MODY

Genetic defects in insulin action (insulin does more than just regualte glucose = higher risk of death)

Gestational diabetes mellitus

Question 24

Why does gestational diabetes mellitus occur?

Answer 24

Transient diabetes that arises during pregnancy (usually during the 2nd trimester)

In some, it occurs because the body cannot produce enough insulin to meet the extra needs of pregnancy

Affects ~5% of all pregnancies

Women who are overweight/obese are at higher risk of gestational diabetes

Question 25

What does gestational diabetes mellitus tell us?

Answer 25

Women who have had GDM = 7x more at risk of developing T2D later in life Esp if they gain weight Could be linked to insulin insufficiency GDm is an early warning of weak beta cell response

Question 26

Why is the criteria for diagnosing gestational diabetes different from other types?

Answer 26

7mM is the limite for T1D and T2D beacuse this is when vascular issues occur But for GDM fasting plasma glucose level of 5.6mM or above is the limit This is becuase it would be dangerous for the unborn child

Question 27

How do hormones respond to fasting?

Answer 27

Glucagon is released from alpha-cell when blood glucose drops Glucagon primarily stimulates hepatic glucose output by enhancing glycogen breakdown and endogenous glucose production (gluconeogensis) Blood glucose levels increase and reduce glucagon production

Question 28

How do hormones respond to food?

Answer 28

Following a meal, blood glucose levels irse Insulin is release from beta-cells when this ocurrs Insulin induces glucose removal from blood and storage in teh liver, adipose, and muscle as glycogen and fat Insulin is cleared by the liver and levels return to basal when blood lgucose levels normalise

Question 29

How is insulin cleared from out system?

Answer 29

Primarily cleared from the body by the liver, which removes a large portion of it during its first pass through the hepatic portal vein, and to a lesser extent by the kidneys through filtration in the glomeruli

Question 30

What is the target cell for T2D therapeutics?

Answer 30

Pancreatic beta-cell

Question 31

What organs does insulin mainly target?

Answer 31

Liver = inhibits gluconeogenesis and promotes GLYCOGEN synthesis Reduces hepatic glucose output Muscle = enhances glucose uptake and storage as glycogen

Question 32

What is the overall action of insulin?

Answer 32

Anabolism = sotrage of energy for times of starvation Promotes glucose uptake into liver Promotes glucose storage as inert glycogen in liver and muscle Promotes use in glycolysis and suppresses gluconeogensis Promotes glucose conversion into FA (which are shipped to adipose) Enhances protein production in muscle Suppresses TAG breakdown in adipose

Question 33

Are insulin and glucagon part of the same signalling pathways?

Answer 33

No, it not simply induction and inhibition fo same molecular pathways

Question 34

Do we ever see insulin and glucagon released at the same time?

Answer 34

During T2DM Indicates severe disruption of signalling sensitivty and regulation of these hormones

Question 35

What needs to be taken into account with drugs for diabetes?

Answer 35

Lifestype and pharmacological interventions are depenent on the TYPE of diabetes Interventions change as disease progresses Addtional drugs added as complication arise, or to prevent compliations There is no drug that produces a cure and for many patients the drugs are not that helpful

Question 36

What are concerns from T1D patients?

Answer 36

Hypoglycameic coma Remembering insulin injection everyday and not getting 'caught out' Glucose monitoring (thumb prick or insert monitor) Fitting into everyday life (sports, work and driving) Sports = increases fuel usage so hypoglycaemia is more likely

Question 37

What is needed to take into account when administering drugs?

Answer 37

Drug-drug interactions hwen taking multiple drugs Pharmacokinetics in patients with renal and vascular problems Patient compliance (aversion to taking drugs, forgetting, wrong dosage) NHS cost

Question 38

What needs to be considered in prevention strategies?

Answer 38

To prevent a disease either change something in the WHOLE population OR Target those at high risk and then give preventative intervention

Question 39

Why is prevention difficult?

Answer 39

Relies on 'treating' those WITHOUT the disease Requires almost constant reinforcement by education

Question 40

What is diseae prevention foucsed on?

Answer 40

Disease risk of a person

Question 41

What is potential T1D prevention as well as treatment?***

Answer 41

Immunotherapy

Question 42

What is potential T2D treatment?***

Answer 42

Targetting obese population Weight loss improves T2D, even in leaner people

Question 43

What group is important to focus on for prevention?

Answer 43

Pre-diabetics

Question 44

How do you identify and engage people at high risk of getting diabetes?

Answer 44

Screen for impaired glucose tolerance (HbA1C), other risk factors (genetics, GDM)

Question 45

How do you alter the obesogenic env?

Answer 45

Sugar tax Always need to have clear evidence base and buy-in from government and food industry

Question 46

How do you deal with health inequalities?

Answer 46

Low income populatoin are highest risk but poorest engagement in current programmes No easy fix Digital innovation and local chamions

Question 47

How do you evaluate if the weight loss programme is working?

Answer 47

Evaluate short term weight improvement Maintained improvement in weight/adiposity should translate to less T2D in 5-10 years (politiciant was faster results) Need long-term clinical follow-up High quality data collection, joined up national approach to intervention allocations and data collection NHS as research facility

Question 48

Defne remission

Answer 48

Signs and symptoms of your disease are reduced Remission can be partial or complete Complete = all signs and symptoms have disappeared

Question 49

What defines diabetes is in remission?

Answer 49

HbA1c dropping below 6.5% without hte need to take any T2D medication

Question 50

Why is prevention so difficult in the NHS?

Answer 50

Limited funding Short-term political cycles Focus on treating immediate health issues rather than long-term prevention Siloed government structures Lack of incentives for preventative care The complex social determinants of health that often lie outside the direct control of the NHS Meaning addressing preventative measures often requires collaboration with other sectors like housing, education, and transport, which can be challenging to coordinate effectively

Question 51

What is evidence that T2DM can be prevented?***

Answer 51

Weight reduction has a strong correlation with improved diabetes

Question 52

What are barriers to prevention of T2DM?***

Answer 52

Identifying and engaging people at high risk of getting diabetes Altering obesogenic env Dealing with health inequalities (minorities, and low income population) Evalutaing if the programme is working (diffucult to see on a long-term scale)

Question 53

What is diabetes insipidus?

Answer 53

Diabetes insipidus is caused by problems with a chemical called arginine vasopressin (AVP), which is also known as antidiuretic hormone (ADH). AVP is produced by the hypothalamus and stored in the pituitary gland until needed. The hypothalamus is an area of the brain that controls mood and appetite. The pituitary gland is located below your brain, behind the bridge of your nose. AVP regulates the level of water in your body by controlling the amount of urine your kidneys produce. When the level of water in your body decreases, your pituitary gland releases AVP to conserve water and stop the production of urine. In diabetes insipidus, AVP fails to properly regulate your body's level of water, and allows too much urine to be produced and passed from your body. There are 2 main types of diabetes insipidus: AVP deficiency (formerly cranial diabetes insipidus) – where the body does not produce enough AVP, so excessive amounts of water are lost in large amounts of urine AVP resistance (formerly nephrogenic diabetes insipidus) – where AVP is produced at the right levels but, for a variety of reasons, the kidneys do not respond to it in the normal way