1a Diabetes Mellitus Flashcards
Describe the normal response to feeding?
- Eat a meal
- Glucose levels in the blood are elevated
- Pancreas releases insulin
- Insulin binds to insulin receptor
- This causes GLUT4 receptors to move to the plasma membrane of the cells
- Therefore glucose is able to pass into the muscle or fat cell
Where are GLUT 4 receptors found?
muscle or adipose tissue
How does GLUT 4 respond to insulin?
It is highly insulin dependant
Where is GLUT 4 found before moving to the ccell membrane?
Found in vesicles -moves from vesicles to membrane in the presence of insulin
What does insulin act as a signal of?
Insulin is a signal you have been fed
What happens to gluconeogenesis when insulin levels are high?
Gluconeogenesis is turned off
What happens to glycogen levels when insulin is released?
Glycogen levels increase as the glucose is stored as glycogen
Why is triglycerides the most useful energy store?
It is fully reduced therefore is the mot efficient energy store
What are NEFAs?
Non-esterified fatty acids
How do triglycerides form?
They form through an esterification reaction of three NEFA’s and a glycerol molecule
What is the purpose of adipocytes?
To store energy
What does lipoprotein lipase do?
Breaks down triglycerides into the glycerol and NEFA molecule so that they can leave circulation and enter into the adipocyte for storage
What affect does insulin have on lipoprotein lipase?
Insulin switches on lipoprotein lipase
What happens to the glycerol in adipose cells from the breakdown of he triglyceride?
Can be converted into glucose - via gluceoneogenesis by conversion into dihydroxyacetone phosphate and then into GALP
What are the effects of insulin in the fed state?
INCREASED:
- Glycogen store
- Glucose uptake
- Triglyceride break down
- protein synthesis
DECREASED:
- Ketogenesis
- gluconeogenesis
-
What is the brains main energy substrate?
Glucose
Can the brain use ketone bodies or fatty acids as a source of energy?
Can use ketone bodies as a last resort, but not fatty acids
Why can fatty acids not be used in the brain as a source of fuel?
The fatty acids cannot pass the blood brain barrier
What happens to insulin levels during starvation?
They fall
What happens to glucose uptake in cells during starvation?
It falls
What happens to hepatic glucose output?
it rises
What happens to lipolysis when insulin levels are low?
Lipolysis is switched on
What happens in lipolysis?
Non esterified fatty acids are released
What happens to the NEFA’s that are released during lipolysis?
They are converted into ketones
What happens to blood pH when ketones are made and why?
Blood pH starts to fall - this is because ketones are slightly acidic
What happens to gluconeogenesis when insulin levels are low?
The liver turns on guconeogenesis
What is hepatic glycogenolysis?
The generation of glucose from stored glycogen in the liver
What effect does low insulin levels have on beta oxidation?
Increases beta oxidation
What is produced in beta oxidation?
acetyl coa which is then used to produce ketone bodies in the starving state
What are the three keone bodies?
Acetone
Acetoacetate
3-beta hydroxybutyrate
Starving for a long period of time results in a sweet, strong smell that you can detect. Why?
Starving state = increased gluconeogenesis, meaning the oxaloacetate which would normally be used in the TCA cycle is being used t make glucose, therefore excess of acetyl CoA - converted into ketone bodies via ketogenesis
What happens in myocytes when insulin levels are low?
no glucose is pumped into muscle cells, so the onboard stores of glycogen are used to make glucose, which then undergoes glycolysis and Krebs cycle to make ATP
What happens to proteolysis when insulin levels are low?
It increases - proteins are broken down into amino acids
What happens to hepativ glucose output when inculin levels are low
It increases
What happens to ketogenesis when insulin levels are low?
It increases
What type of disease is Diabetes Mellitus?
An autoimmune condition
What is destroyed in T1DM
The ISLET cells
What word is used to describe the glucose levels of those with T1DM?
Hyperglycemia
Why does ketone production occur in T1DM?
There is a lack of insulin, therefore your body will behave as if it starving, and will increase ketone body production for energy
What is ketoacidosis?
When you have very large amounts of ketone bodies so they become acidic
If you have the presence of ketone, which type of diabetes do you have?
Type 1
What is the pH range for patients with ketoacidosis?
A pH less than 7.3
What are some complications of ketoacidosis?
Patients with ketoacidosis experience low pH in the blood as the ketones are acidic - a low pH is associated with decreased brain function, which can make the patient unconscious, and experience a low mood, and can also lead to death
What are some osmotic symptoms of T1DM?
Polyuria, polydipsia and nocturia
What is polyuria?
A lot of urine
What is polydipsia?
Drinking a lot of water as you are thirsty often
What is nocturia?
Waking up at night because you have to urinate
What level does resting glucose have to be in order to be diagnosed with T1DM?
> 11.1mmol/L
What level does fasting glucose have to be in order for a diagnosis of T1DM to be made?
> 7.0mmol/L
Above what value is HbA1c considered high?
> 48mmol/mol
What are the values for the diagnosis of diabeteic ketoacidosis?
pH < 7.3, high levels of ketones, HCO3 < 15mmol/L, glucose > 11
How many positive tests do you require for the diagnosis of T1DM?
2 Positive tests or 1 positive test and osmotic symptoms
Why is measuring C-peptide a useful diagnostic test?
C peptide is cleaved from pro-insulin along with insulin. Therefore little c peptide indicates little insulin / pancreas
What antibodies can be tested for a T1DM diagnosis?
GAD and IA2
How do you treat T1DM?
Replace insulin through injections at a specific dose relative to the meal you are going to eat
What happens if you inject insulin without eating food?
Insulin results in more glucose being absorbed, so much so that you become hypoglycaemic
What is hypoglycaemia?
When blood sugars are very low
What happens to the brain during hypoglycaemia?
Since insulin is present, ketone production is stopped. But you have no fuel for brain now, so brain cannot function - results in confusion and unconsciousness
What four things increase to counter act hypoglycaemia?
Glucagon, catecholamines, cortisol and growth hormone
What happens to the hepatic glucose output when the body induces the counter regulatory response to hypoglycaemia?
It increases with glycogenolysis and gluconeogenesis
What is impaired awareness of hypoglycaemia?
The reduced ability to recognize symptoms of hypoglycaemia due to loss of counter regulatory response which leads to recurrent hypo.
What might someone who is having a hypo feel?
Confused, aggressive, irrational
Autonomic symptoms of hypoglycaemia?
Sweating, pallor, palpitations and shaking
What is the definition of severe hypoglycaemia?
An episode in which a person requires third party assistance to treat
What are some neuroglycopenic symptoms of hypoglycaemia?
Slurred speech, poor vision, confusion, seizures and loss of consciousness
What can you give a patient suffering with unconsciousness due to a hypo?
1mg glucagon injection
What can be given to patients suffering from an acute hypo episode?
Jelly babies, lucozade, glucogel
What is T2DM?
Where you have insulin resistance in the liver, muscle and adipose issue, however enough insulin to suppress ketogenesis and proteolysis
Will you ever find ketoacidosis in patients with T2DM?
No
What are some signs and symptoms of T2DM?
High fasting glucose >7 mmol/L
High random glucose > 11.1 mmol/L
Large waist circumference
Hypertension (135/80 mmHg)
Which type of diabetes is associated with weight gain and loss respectively?
Gain = T2
Loss = T1
Why does T1DM result in polyuria?
The excess glucose ends up in the urine, which draws more water into the urine via osmosis, hence the volume of urine increases
What are the risk factors for T2DM?
Age, PCOS, High BMI, family history, ethnicity, inactivity
What are the four ways to manage T1DM?
Education
Technology
Exogenous insulin
Self monitoring of insulin
What is the basal bolus regime for insulin?
Basal (long acting) insulin is given once for long actin
Bolus is given throughout day before meals in order to manage the rises in glucose after meals
What four ways can T2DM be managed?
Education
Diet
Exercise
Oral medication - to stimulate the pancreas to increase insulin production
What other microvascular systems can be affected due to diabetes?
Retinopathy
Neuropathy
Nephropathy
What macro vascular systems can be affected by T2DM?
Cardiopathy eg heart attack
What is dyslipidemia?
Disturbances in fat metabolism cause changes in the lipid concentration in the blood
What is diabetic retinopathy?
High glucose levels in the blood result in damage to the blood vessels which supply the retina
