Type 2 diabetes - 141 Flashcards
Describe diabetes
A disorder of carbohydrate metabolism in which sugars in the body are not oxidised to produce energy due to a lack of (or resistance to) insulin.
This leads to hyperglycaemia
Name some common signs and symptoms of diabetes
Thirst, weight loss, polyuria.
Other symptoms include blurred vision
How is type 2 diabetes different to type 1?
In type 2 the pancreas retains some ability to produce insulin, however the body becomes resistant to its effect
How is diabetes diagnosed?
Resting plasma glucose -> 11.1mmol/l
Fasting plasma glucose -> 7mmol/l
Oral glucose tolerance test -> 75gm oral load after 10hr fast
HbA1c
** Diabetes diagnosed by either venous glucose OR HbA1c levels
Name some pros and cons for using glucose levels as a diagnostic tool for diabetes
Pros: Diabetes is a glucose disease, large amount of data, international comparison, cheap, accurate
Cons: Patient needs to fast, patient cannot smoke, pre-analytical problems.
Name some pros and cons of using HbA1c as a diagnostic tool for diabetes
Pros: No fasting, stable, time averaged,
Cons: Influenced by many factors e.g. pregnancy, anaemia, renal failure, blood transfusion
Describe the process of insulin production
Preproinsulin -> proinsulin -> insulin + C-peptide
How does the 1st phase insulin response differ to the 2nd phase insulin response?
The 1st phase response is rapid and consists of pre-made insulin. This is followed by the 2nd phase which is slower but lasts much longer than the 1st phase.
In type 2 diabetes which phase of insulin release is lost?
The 1st phase -> as the diabetes progresses the patient also loses the 2nd phase
What is GLP-1?
An incretin
What does GLP-1 do?
It is secreted from gut cells in response to increased glucose levels. GLP-1 binds itself to beta cell which increases insulin release and decreases glucagon release. The increased insulin transports glucose to the liver to be stored
Do patients with T2 diabetes have increased or decreased incretins?
Decreased - not enough insulin is produced and too much glucagon is produced
When there is not enough glucose present for an energy source what happens?
The body uses ketone bodies for energy. This can disturbance the acid/base balance and result in ketosis, eventually resulting in a diabetic coma
What a patient with impaired glucose tolerance’s glucose and insulin levels be?
Both will be raised
What is the role of GLUT4?
It transports glucose into tissues.
How is GLUT4 made? What is the consequence of this in diabetes?
It is made when PI-3K is phosphorylated.
In diabetic patients PI-3K is not phosphorylated, and so glucose is not transported into tissues.
What is the link between diabetes and increased risk of diseases such as cancer and CV events?
Insulin is a growth factor, when it isn’t taken into cells it is involved in inflammatory and growth processes.
What receptors are involved in glucose reabsorption from the PCT in the kidney?
SGLT2 receptors - and some SGLT1 receptors
Are SGLT2 receptors up or down-regulated in T2 diabetes?
Up regulated -> leads to a 10% increase in reabsorption
What drugs can be given to diabetics to help prevent as much glucose reabsorption? What are the side effects?
SGLT2 inhibitors. These can cause UTIs and dehydration. Recommend that patients drink at least 2L of water a day.
Name some therapies for T2 diabetes
- Biguanides -> METFORMIN. Improves insulin action.
- Sulphonylureas -> gliclazide. Increases insulin production
What are some side effects for metformin?
GI disturbances
Name some side effects of sulphonylureas, e.g. glicazide
Weight gain and hypoglycaemia
Give an example of a metiglinide (insulin secretagogue)
Repaglinide.
Side effects = mild hypoglycaemia and GI disturbances
What do thiazolidinediones do?
Increase peripheral insulin sensitivity. They have no effect in the absense of circulating insulin. They can cause peripheral oedema and anaemia
What is relevant about familial renal glycosuria when discussing diabetes?
It causes glucose to be in urine.
Name some microvascular complications of diabetes
- Retinopathy
- Nephropathy
- Neuropathy
State some macrovascular complications of diabetes
Coronary artery disease
Cerebrovascular disease
Peripheral arterial disease
What is the main cause of death in diabetic patients?
Premature cardiovascular disease
Name some consequences of hyperglycaemia
- Increased blood coagulation
- Increased HDL-c catabolism
- Increased insulin resistance
- Decreased plaque stability
What is the current advice for diabetic patients?
- Obtain tight glycaemia control from the beginning in order to keep the ‘legacy effect’.
- Keep bp controlled from the start (<130/80)
- Statin therapy from age 40+
- Anti-platelet therapy for secondary prevention
