Diabetes Flashcards
How does the body respond to elevated blood sugar levels?
Beta cells in the pancreas secrete insulin which promotes tissue uptake of glucose and glycogen formation in the liver to decrease blood sugar levels
How does the body respond to lowered blood sugar levels?
Alpha cells in the pancreas secrete glucagon, which promotes glycogenolysis in the liver, which releases glucose into the blood to increase blood sugar levels
What is the mechanism behind insulin release by beta cells?
Cell depolarisation initiates insulin release, similar to a nerve cell releasing neurotransmitters
- Glucose enters the cell, and ATP production increases
- ATP increase causes potassium channels to go up, causing cell voltage to increase
- Increase in voltage causes voltage-gated calcium channels to open, depolarising the cell
- Cell depolarisation results in insulin release
What is type 1 diabetes?
What is it caused by?
It is an autoimmune disorder that causes the destruction of beta cells by immune cells, meaning less or no insulin is produced
It is caused by a combination of genetic susceptibility (creating an abnormal major histocompatibility complex) and an environmental factor
(Often preceded by a viral infection, which triggers the immune system)
What percentage of beta cells must be destroyed for Type 1 diabetes symptoms to arise?
70%
In type 1 diabetes, what do B-cells produce antibodies against?
What are these antibodies?
B-cells produce antibodies against beta cells and insulin
Antibodies:
- Islet cell antibodies (ICA)
- Auto Insulin antibodies (children only)
- Glutamine Decarboxylase (GAD)
- Insulin antigen 2 specifc
What happens if cells are deprived of glucose?
What is the byproduct of this?
Glycolysis can’t occur, so the citric acid cycle, electron transport chain and ATP generation (oxidative phosphorylation) cannot occur
Acetyl CoA cannot enter citric acid cycle so is converted into ketone bodies which are released into the bloodstream
What do ketone bodies do when released into the blood?
They make the blood acidic (ketoacidosis)
What are the signs and symptoms of diabetic ketoacidosis?
Thirst
Hunger
Rapid deep breathing (Kussmaul respirations)
Acetone breath
Weight loss
Muscle loss
Low blood pH
High blood glucose
What additional electrolyte imbalance can acidosis lead to?
Hypokalemia (High concentration of hydrogen ions in blood automatically flow into cells, changing cellular charge and triggering potassium channels to open and potassium to get lost in urine)
What are the management strategies for diabetic ketoacidosis?
Fluid replacement - Glucose and water lost through kidneys
Potassium replacement
Insulin - reduce DKA
What are the major risk factors for type 2 diabetes?
Obesity
Hypertension
Dyslipidaemia
- Elevated triglycerides (Should be in adipose cells not bloodstream)
- Low HDL cholesterol (less made by liver)
- Elevated LDL cholesterol (More made in liver –> Atherosclerosis)
Lack of physical activity
What are some minor risk factors for diabetes?
Age
Genetic/family history
Ethnicity
- Pacific populations (15%)
- Maori population (9%)
- Asian (8% - higher in south-east Asian populations)
- European (5%)
How is insulin resistance triggered?
The liver gets inundated with triglycerides, which triggers the downregulation of insulin receptor production in the liver cells.
The liver produces more VLDL particles to transport these excess triglycerides to other cells, which also then downregulate insulin receptor production
What are the complications of diabetes?
Coronary heart disease
Nephropathy
Peripheral vascular disease
Neuropathy
Retinopathy
What are symptoms of hyperglycaemia?
Weight loss
Tiredness
Increased thirst
Increased urination
Blurred vision
Recurrent infections
Poor wound healing
What test is used to diagnose diabetes?
What does it measure?
HbA1c test which measures the average amount of blood glucose over the previous 8-12 weeks, alongside symptoms
It measures how much glucose is stuck on red blood cells (glycated haemoglobin)
What is c-peptide and how is it linked to Type 1 diabetes diagnosis?
C-peptide is a byproduct of insulin production and is made in equal amounts as insulin. A measure of c-peptide is analogous to a measure of insulin and, combined with auto-antibodies, can be used to diagnose type 1 diabetes
What is the treatment for type 1 diabetes?
Insulin, 24hr cover
complex regimens required to mimic pancreatic function
What is the treatment for type 2 diabetes?
Blood sugar control
- Medications
- Healthy Diet
- Increased Activity
Target factors contributing to cardiovascular disease
- BP
- High cholesterol
- Smoking
- Obesity/Inactivity
Screening/treatment for long term complications
- Retinal screening every 1-2 years
- Blood and urine tests for nephropathy
- Foot assessments
- CVD Risk assessments
What are some type 2 diabetes management medications?
Metformin - decreases gluconeogenesis and increases peripheral insulin sensitivity
Sulphonylureas - Increases insulin release from beta cells
Vildagliptin (DPP-4 inhibitor)
- DPP-4 is an enzyme that cleaves GLP-1 glucagon-like peptide
- Vildagliptin increases GLP-1 levels, increasing insulin production and reduces glucagon secretion from alpha cells
What is peripheral vascular disease?
Occlusion of arteries supplying blood to the extremities by atherosclerosis leading to reduced perfusion (From femoral artery down = peripheral)
What are the risk factors for peripheral vascular disease?
Advanced age (≥60yo)
Smoking
Diabetes
Hypertension
Dyslipidaemia
Family history/genetic predisposition
Obesity/Sedentary lifestyle
What are signs and symptoms of peripheral vascular disease?
Claudication
- Pain, aching or fatigue in working skeletal muscles (supply/demand of O2)
Pain at rest
Loss of hair on legs
- Redirection of limited blood from the skin
Ischaemic pain
Skin changes
- Shiny due to lack of skin perfusion
- Colour change (not normal/healthy)
Ulceration
Gangrene formation
What are the signs and symptoms of acute limb Ischaemia?
Pain
Pallor
Pulselessness
Poikilothermic (Coldness)
Paralysis
Paraesthesia
What are some diagnostic investigations for peripheral vascular disease?
Blood tests
Ankle Brachial Pressure Index (Looking at circulation)
Duplex ultrasound
MRA (Magnetic resonance angiography)
CT scan
Angiogram
What is the treatment for peripheral vascular disease?
Lifestyle changes
- Increase activity/lose weight
- Healthy diet
- No smoking
- Reduce Alcohol intake
Pharmacotherapy
Angioplasty
Stenting
Surgical revascularization surgery
Amputation (If it’s really, really bad)
