8. Diabetes Mellitus Flashcards
(41 cards)
What is diabetes mellitus?
Chronic non-communicable disease characterised by hyperglycaemia
What causes diabetes mellitus and what are the consequences (brief)?
Caused by relative insulin deficiency or resistance or both
Usually irreversible
Late complications of diabetes mellitus result in reduced life expectancy and major health costs
What is the prevalence of diabetes in the UK?
Currently 3.5 million people diagnosed with this in the UK
Numbers are continually increasing each year
What is type 1 diabetes and how is it caused?
Chronic autoimmune disease
Characterised by immune (t-cell) mediated disruption of the pancreatic Beta cells within the islets of Langerhans
Autoantibodies act against the Beta cells in the islets and there is infiltration of the pancreas islets by mononuclear cells
This results in an insulin deficiency as the Beta cells cannot produce insulin
Describe the hereditary aspect of type 1 diabetes and the age of presentation
Prominent disease in childhood and generally in younger patients (<30 years old) but can present at any age
The genetic basis of the disease is not fully understood - not genetically predetermined but increased susceptibility to the disease can be inherited
How is type 1 diabetes treated?
There is a constant need for insulin injections
Immunosuppression may be administered as this acts to delay the Beta cell disruption
What is type 2 diabetes?
Chronic, progressive disease characterised by abnormal insulin action and secretion as well as elevated insulin resistance
Most common form of diabetes (85-90% of all cases of diabetes)
SO compare the cause of type 1 diabetes to type 2 diabetes
Type 1 - due to destruction of beta cells and lack of secretion of insulin
Type 2 - Beta cells are still functioning and insulin is being secreted but it is not sensed by the receptors and so the actions mediated by insulin is not correctly elicited BUT there is also some level of a lack of insulin secretion by the beta cells - this may be due to exhaustion of the beta cells after trying to compensate via increased production of insulin
Describe the hereditary aspect of type 2 diabetes and the age of presentation
Used to be more prominent in older patients - greater than 30 years
BUT is now becoming more and more common in younger populations due to increased levels of obesity (one of the major risk factors)
There is a strong genetic component but again this is not fully understood - currently a lot of research being carried out relating to this
What are the risk factors for type 2 diabetes?
Obesity - BMI greater than 31 leads to a 40-fold increased risk
Family history
Increasing age
Ethnicity
What is meant by insulin resistance?
This is when there are reduced responses to the hormone insulin
SO the hormone is circulating but the target tissues are not responding to it properly e.g. due to a reduction of insulin receptors
Essentially what is occurring in type 2 diabetes
Give a suggested mechanism of insulin resistance
Insulin binds to it’s receptor insulin receptor substrate (IRS)
This must then be phosphorylated by tyrosine to activate the pathway of events for insulin signalling i.e. for the translocation of the receptor
BUT in insulin resistance, has been found that the IRS isn’t phosphorylated by the tyrosine kinase as it should be and so the pathway is stopped
What role do macrophages play on insulin resistance?
Infiltrating macrophages into adipose tissue - these can release cytokines which can contribute to insulin resistance
What are the causes of insulin resistance?
Explain these
Obesity:
Accumulation of lipids and their metabolites or increased circulation of free fatty acids
Chronic inflammation
Altered adipokine levels
Hyperinsulinaemia:
Increases lipid synthesis and exacerbates insulin release
Does insulin resistance always lead to diabetes?
NO - diabetes does not always develop because generally there will be islet compensation
E.g. if the insulin resistance is because of e.g. pregnancy or body weight gain then islet compensation will occur to counter this
What is islet compensation ?
This is where new beta cells can be generated in response to insulin resistance
They may also increase in size and can increase their ability to secrete insulin
This will generally allow the body to maintain the normal glucose level (3-5mm/L) in instances of e.g. pregnancy or increased body weight
What is the role of islet compensation in diabetics?
Diabetics do not have islet compensation
In contrast, they will actually produce fewer levels and smaller beta cells due to abnormalities and hence fewer levels of insulin synthesised/secreted
This is why some obese people will not develop diebetes - they have islet compensation but those who do not have islet compensation have a predisposition to developing diabetes
Type 2 diabetes –> dysfunction of the beta cells
Apart from type 1 and type 2, what are the other forms of diabetes mellitus?
Maturity onset diabetes of the young (MODY) - autosomal dominant inheritance of mutated gene resulting in disrupted insulin production - but this is very rare
Gestational diabetes - occurs in 2-6% of pregnancies - insulin resistance is not compensated - increased risk of subsequent type 2 diabetes
Latent autoimmune diabetes of adults (LADA) - have markers of autoimmunity and there is a progression to insulin dependency faster than type 2 diabetes
How is type 2 diabetes diagnosed?
One abnormal plasma glucose concentration in the presence of symptoms OR in asymptomatic people, two fasting venous plasma glucose samples in the abnormal range
What investigation can be used to diagnose type 2 diabetes?
HbA1c - haemoglobin is affected in people that have diabetes - becomes glycosylated so can measure the levels of glycosylated haemoglobin in the blood
This is a reliable measure but it can be expensive in some parts of the world - this is reliable because the glcoysylated haemoglobin is more stable than the blood glucose
Gives you information on the levels of blood glucose for the past three months
What is the treatment for type 2 diabetes?
Target the insulin resistance of the beta cell dysfunction - certain drugs act to do this DPP-4 inhibitors or SGLT2 inhibitors
e.g. can enhance the sensitivity so that target tissues are more likely yo so they e.g. increase glucose uptake
Inhibit gluconeogensis in the liver e.g. metformin - results in increased glucose uptake in the muscles
Drugs to stimulate insulin secretion e.g. act on the K+ channels of the beta cells
OR may have drugs that act on the GLP-1 hormone - this is a hormone which can increase insulin secretion and also reduces glucagon secretion
What are the acute complications of diabetes?
Ketoacidosis - most common in type 2 but can occcur in type 1
Hypoglycaemia
What is ketoacidosis?
Due to a lack of insulin, the metabolism will be shifted to fatty acid consumption
Continual use of fatty acids for fuel will result in the production of ketone bodies from acetyl coA - the ketone bodies then dissociate into anions and H+ and this leads to ketoacidosis in the body
This can lead to increased levels of blood and urine acid, can lead to dehydration, coma and death
Why can hypoglycaemia occur?
When treating the hyperglycaemia in diabetes, may result in the utilisation of too much glucose relative to the inhibition of glucose release
Other causes include:
Alcohol excess - gluconeogenesis is inhibited at the level of lactate dehydrogenase
Insulinoma - tumour of pancreatic beta cells
Excessive exercise leading to the increased utilisation of glucose
