Diabetes Flashcards
What are the symptoms of all types of diabetes?
- Urinating more
- Feeling thirsty (dehydration)
- Feeling tired –> dehydration, lack of glucose in the cells so not metabolised into energy, losing glycogen stores
- Unexplained weight loss –> using glycogen stores, dehydration, for each gram of glycogen the body retains 3g of water - low levels of body water –> body not using protein or fat stores (more T1)
- Cuts or wounds that heal slowly –> glucose excess in circulation can damage endothelial cells disturbing the blood flow and impairing the activation of some immune cells –> glycosylated haemoglobin prevents transport of oxygen making it harder for oxygen to reach wound sites to help with blood clotting.
- Blurred vision –> retinopathy from an excess of glucose, glucose can damage capillaries affecting vision
The body tries to get rid of glucose from the body, excreting it through urine. A Dipstick test can identify glucose in urine. Glucose in the kidney.
Dehydration from frequent urination can lead to increased thirst.
Explain type 1 diabetes
An autoimmune disease where pancreas cells are destroyed leading to no insulin production.
Meaning that glucose levels build up in blood and are not taken up into cells.
T1 Diabetics require insulin injections at mealtimes so their body is able to utilise glucose and reduce levels in the bloodstream post-eating.
There is a quick onset of condition
Cause unknown could be
- Immunological factors
- Genetic factors –> first-degree relative increases the risk about 15-20% higher
- Environmental factors
In diagnosis fasting, plasma glucose is >7.0mmol/L
HbA1c >48mmol/mol
What are the difference between type 1 and type 2?
Type 1 has a quick onset, T2 has a slow onset
What is gestational diabetes?
Diabetes that effects those in their third trimester of pregnancy
Usually disappears after the baby is born
Higher sensitivity to insulin
18% of women
More likely to develop T2 diabetes later on in life
How is diabetes diagnosed?
Blood tests:
- fasting plasma glucose >7.0mmol/L
- random venous plasma glucose concentration >11.1mmol/L
- HbA1c >48mmol/mol
Urine:
- High ketone levels
- High glucose levels
Insulin in blood:
- first stages of T2D, blood glucose is normal
- insulin high
Oral glucose tolerance test
- drinking 75g of glucose
- calculating the area of the curve can say if someone is more sensitive to glucose or not
Intravenous glucose tolerance test
- glucose in circulation –> removing digestion and absorption process
- tests how the pancreas releases and uses insulin
Describe the development of type 2 diabetes
Undetectable preclinical stage
1. Biological onset
Detectable preclinical stage
2. Detectable pre-clinical stage
3. Symptoms develop
- Microvascular complications
- Major disability or death
What are the glucose and HbA1c levels in that normal , pre, and diabetics?
Glucose:
- Normal –> 3.5 - 5.5mmol/L
- Pre-diabetes –> 5.6 - 7mmol/L
- Diabetes –> >7.0mmol/L
HbA1c:
- Normal –> <42 mmol/mol
- Pre-diabetes –> 42-48 mmol/mol
- Diabetes –> >48 mmol/mol
What is glycosylated haemoglobin?
When glucose binds to haemoglobin and condenses –> forming an irreversible bond –> lowers the ability of haemoglobin to transport oxygen
The more glycosylated haemoglobin the lower ability to transport oxygen –> lead to kidney damage, complications in wound healing.
Occurs normally at low levels in everyone, in diabetes this is a high level.
How does body fat accumulation cause damage?
The accumulation of fat (adipose tissue) in obesity leads to hypertrophy where the adipocytes get much larger until it reaches the point where they can’t get larger so they increase the number of adipocytes and hyperplasia. This leads to damage, which increases oxidative stress and therefore metabolic dysfunction.
Metabolic dysfunction is associated with leptin resistance
Discuss leptin and leptin resistance
Leptin helps to suppress appetite
In leptin resistance this is downregulated, increasing the individual’s appetite. Lower levels in the brain, some changes in the blood-brain barrier.
Central hypoleptinaemia –> low levels in the brain
Peripheral hyperleptinaemia –> high levels in the blood
Changes in blood-brain barrier permeability.
A disrupted pathway means that the brain doesn’t receive signals to say that the body is full.
Peripheral hormones are not signaling the brain normally.
Higher adipose levels = higher leptin amounts
However, leptin is not as functional
If restricting energy intake, lower levels of leptin will be produced –> peripheral hypoleptinaemia –> central hypoleptinaemia –> increased appetite –> up-regulating appetite response –> increasing ghrelin levels
- prolonged response can lead to some adaptations which facilitate lower energy intake from diet.
How are cytokines related to obesity?
With high levels of adipose tissue, cytokines are highly produced. Adipose tissue damage leads to an up-regulation of immune cells and cytokines.
Main cytokines produced in adipose tissue
- Leptin
- Adiponectin –> metabolic control
- TNFa and IL6 –> inflammatory cytokines, upregulate immune cells and help destroy damage and avoid further damage. On a chronic level this is dangerous
- Retinol binding protein
What are the different types of cytokines?
Autocrine
- Cytokine that binds to receptor on cell that secreted it
Paracrine
- Cytokine binds to receptors on nearby cells, e.g. in liver
Endocrine
- Cytokine binds cells in distant parts of the body e.g. in circulation to brain
What is leptin?
How does it work?
Satiety cytokine
- Alone or with insulin can dramatically improve glycaemic control
- Leptin administration directly into the brain, or leptin overexpression in the brain have beneficial effects on glucose homeostasis
- These effects appear to be mediated at the arcuate nucleus of the hypothalamus
Mechanism
- Fat tissue releases leptin into the bloodstream
- Through BBB to the hypothalamus
- Controls entry balance –> satiety response
Describe the adipo-insular negative feedback loop
Healthy physiological status:
Food –> pancreas releases insulin (after <5 minutes) –> main tissues that uptake glucose, muscle, liver, and adipose tissue –> when insulin binds, leptin synthesis and release is increased after 20-30minutes –> higher leptin levels signal pancreas –> down-regulates insulin synthesis
Glucose –> Pancreas –> Insulin upregulated –> leptin –> insulin downregulated
NEGATIVE FEEDBACK LOOP
Slow eating can help with energy intake control due to leptin release
How does hyperleptinaemia affect insulin?
Insulin upregulates leptin production from adipose tissue after food intake. With high levels of insulin, more leptin is needed to be produced from adipose tissue (high levels of adipose tissue increase leptin production) –> leading to peripheral hyperleptinaemia
This leptin is not very functional and does not signal the pancreas to stop insulin release
Dysregulated adipoinsular feedback loop
