Patho & Treatment - Diabetes Flashcards
(41 cards)
What is diabetes mellitus?
The loss of glucose homeostasis i.e. a failure of plasma glucose levels to remain within a normal homeostatic range of 4 -6 mmol/L
Abnormal fat, carbohydrate and protein metabolism due to defects in insulin secretion and action
Hyperglycaemia = too much glucose Dyslipidaemia = too much lipids in the blood (drives atherosclerosis)
How is normal glucose homeostasis maintained?
Glucose homeostasis is normally maintained by the interaction between glucagon & insulin which are both stored & released in the Islets of Langerhans in the pancreas
Describe which cells manufacture and secrete insulin and glucagon?
Alpha cells - secretes glucagon
Beta cells - manufacture and secrete insulin
Describe how the hormone glucagon works
Glucagon is released from the pancreas when blood glucose levels falls
Glucagon acts on the liver to break down glycogen to glucose (glycogenolysis)
Liver releases glucose into the blood system i.e. when this occurs blood glucose levels rise bringing it back into the homeostatic range
Describe how the hormone insulin works
Insulin is released from the pancreas when blood glucose levels rise
Insulin promotes the uptake of glucose into adipocytes, cardiac and skeletal muscle cells to be used as an energy source. In the liver it converts glucose to glycogen and stores it there
What is the difference between type 1 and type 2 diabetes?
Type 1 diabetes - inability to secrete insulin (beta cells in Islet of Langerhan) - blood glucose levels rise.
Glucose cannot be used as an energy source
Type 2 diabetes: receptors, on cell membrane of adipocytes on skeletal and cardiac muscle cells and liver cells, become less sensitive to insulin which inhibits the ability of cells to remove glucose from the blood. Long term there is beta cell failure. This causes hyperglycaemia
What are the 8 types of diabetes mellitus?
Type 1
Type 2
Gestational - mothers are at greater risk of developing type 2 diabetes. Baby can gain too much weight making them at higher risk of developing brain trauma during delivery (they also are at a higher risk of developing obesity and type 2 diabetes later in life)
Congenital - babies are born with no functioning beta cells
CF - related - as CF disrupts functioning of the pancreas
Secondary - e.g. an infection within the pancreas affecting the beta cells
LADA - Latent autoimmune diabetes
Diabetes MODY - maturity onset type 2 diabetes (no obesity)
What are the possible causes of type 1 diabetes?
What aged people does it occur in?
Possibly caused by autoimmune, genetic, viral or bacteria causing beta cells in pancreas
Insulin cells in liver, skeletal- cardiac muscle, liver adipocytes are not affected
<40 years - usually manifests in 13 year olds
What are possible causes of type 2 diabetes?
Poor lifestyle causing insulin-receptor resistance
Progressive beta cell failure occurs after long-term type 2 diabetes
Can babies and children get obesity?
Yes both can
What are the 3 physiological responses that occur due to lack of insulin?
The body compensates by increasing beta cell activity (called hyperinsulinaemia)
Later in the disease insulin resistance continues to grow and beta cell exhaustion occurs
1. Excess glucose is converted to fat and stored within adipocytes in the presence of insulin
2. When there is a lack of insulin, accelerated lipolysis occurs liberating free fatty acids and this increases low density lipoproteins (LDLs) in the blood
3. Abnormal release of glucagon (glucagon stimulates liver to break down glucose) which stimulates appetite
How do you prevent diabetes or reverse diabetes to pre-diabetes?
- Weight management – diet & exercise
2. CRF – exercise – maintains receptor sensitivities
What initiates insulin receptor resistance?
Inflammatory mediators and adipokines (cytokines released by adipose tissue) arising from VAT decrease insulin receptor sensitivity and increase insulin resistance
VAT (visceral adipose tissue) is an inflammatory tissue and is metabolically active
VAT is created by excess calories which cause adipocytes to increase in size
Describe how inflammatory mediators cause insulin receptor resistance
Macrophages become active and release TNF alpha, CRP and IL6 which blunt sensitivity of insulin receptors
Resistin (is an adipokine - i.e. is released from adipocytes). It increases insulin receptor resistance. The more VAT present the more resistin is secreted.It promotes the liver to convert free fatty acids to LDLs causing dislipidoemia
Adiponectin (an adipokine) acts on insulin receptors maintaining their sensitivity levels. As an individual expands their VAT the production of adiponectin is decreased
Lack of insulin, fat cells undergo rapid lipolysis which creates free fatty acids. These FFAs increase insulin receptor resistance. Resistin encourages the liver to breakdown FFAs (free fatty acids) to LDLs. Increased LDLs cause atherosclerosis
How does VAT affect hypertension?
VAT secretes leptin and angiotensin 2 which drives up blood pressure
What are the weight features of with type 2 diabetes?
- tend to have high waist circumferences & W:H ratios
- central adiposity (VAT)
- tend to have high BMI > 25 black & white populations or > 23 Asians
- very little subcutaneous adipose tissue (SCAT) but high VAT- common in Asian populations
What occurs when hyperinsulinaemia progresses?
The inflammatory mediators released by VAT (CRP, TNF-alpha, IL-6) induce apoptosis of beta cells in the Islets of Langerhan
This continues until there is no functioning beta cells left
What is the link between type 2 diabetes and atherosclerosis?
- VAT & atherosclerosis –> in absence of insulin: FFA conversion to LDLs
- Hyperglycaemia causes insulin resistance, abnormal activation of glucagon and endothelial wall damage.
Excess glucose in the blood comes in contact with and binds to proteins and lipids on the arteriole endothelium which cause an inflammatory response. Hyperglycaemia causes glycosylation of proteins and lipids in capillary endothelium which causes the release of advanced glycation end-products (AGEs). AGEs are pro-inflammatory and cause endothelal damage and dysfunction and also cause atherosclerosis
What 3 types of tests are used to diagnose diabetes?
Fasting blood glucose test
Random blood glucose test
Oral glucose tolerance test (OGTT) - giving them a bolus of glucose in their mouth. Would expect them to secrete insulin within 2hr and to uptake that glucose very quickly
- These methods are used to monitor their blood glucose throughout the day
How would you monitor the glycaemic health of an individual long term?
% of glycosylated haemoglobin in the blood (HbA1c)
The more blood glucose present the higher the % of glycosylated haemoglobin
What are the causes of hypoglycaemia?
Miscalculation of insulin medication in type 1 diabetes (as they have no insulin production) or in type 2 diabetes who have very poor or no insulin production)
What is the signs of hypoglycaemia?
Sympathetic n.s. symptoms e.g. anxiety, dizziness, confusion, cloudy vision, headaches, hunger, sweating, tremors
- Convulsions, loss of consciousness, coma, death
How do you treat hypoglycaemia?
If exercising a diabetic patient how would you ensure they don’t become hypoglycaemic?
Eat/drink carbohydrates
IV glucose
Subcutaneous glucagon injection
Pre-exercise glucose test
What does severe hyperglycaemia cause?
Diabetic ketoacidosis (DKA)
