10. Diabetes Flashcards
What is diabetes?
Metabolic disorder characterised by hyperglycaemia due to insulin deficiency, insulin resistance or both.
What is type 1 diabetes characterised by?
Progressive loss of all or most of the pancreatic beta cells due to autoimmune attack.
When is type 1 diabetes usually diagnosed?
Children and teenage years
How is type 1 diabetes treated?
Life-long insulin treatment (must be injected)
Dietary management and exercise also key components
What is the cause of hyperglycaemia in type 2 diabetes?
Progressive loss of beta cells along with disorders of insulin secretion and resistance.
When is type 2 diabetes usually diagnosed?
Older patients, may be present for a long time before diagnosed.
How is type 2 diabetes managed?
- Diet
- Oral hypoglycaemia drugs
- Eventually insulin as it progresses
List the classic triad of symptoms you would expect to see in a patient with Type 1 diabetes mellitus.
- Polyuria
- Polydipsia
- Weight loss
Why is polyuria a feature of diabetes?
Glucose levels exceed renal threshold, and some glucose is excreted. Less water is reabsorbed into the nephron to account for the increased osmotic load.
Why is polydipsia a feature of diabetes?
Excessive water loss from polyuria and osmotic effects of glucose on the thirst centre.
Why is weight loss a feature of type 1 diabetes?
Increased proteolysis and lipolysis
How is diabetes easily diagnosed?
Measuring plasma glucose levels
Urine ketone and glucose levels
What life threatening crisis can untreated type 1 diabetes lead to?
Diabetic ketoacidosis
What affect does insulin deficiency have on the metabolism?
Rapid lipolysis, excess FA converted to ketone bodies in the liver.
How can type 1 diabetes result in ketoacidosis?
Increased rate of lipolysis in adipose tissue which releases large amounts of fatty acids, the substrate for ketone body formation. H+ associated with the ketones produces a metabolic acidosis.
Activation of the ketogenic enzymes in the liver.
How can ketoacidosis be detected on the breath?
Acetone is a volatile ketone body that can be smelt on the patients breath
What are the symptoms of ketoacidosis?
Prostration - exhaustion Hyperventilation Nausea and vomiting Dehydration Abdo pain
Rather than the triad, which symptoms are patients with Type 2 diabetes more likely to be present with?
Lack of energy
Persistant infections (genital thrush)
Slow healing
Visual problems
If diet management fails, what oral hypoglycaemic drugs can be used to treat type 2 diabetes?
Sulphonylurea - increase insulin release from beta cells
Metformin - reduces gluconeogenesis
In which tissues is uptake of glucose determined purely by extracellular glucose concentration, what are the complications of this?
Peripheral nerves, eye and kidney.
During hyperglycaemia, the intracellular [glucose] increases and it metabolised by aldose reductase.
This reaction depletes NADH, increases disulphide bond formation in proteins, altering structure and function.
Accumulation of product sorbitol causes osmotic damage.
What changes to the plasma proteins occur in persistant hyperglycaemia?
Glycation of plasma proteins such as lipoproteins and haemoglobin.
How goes glycation of plasma proteins affect their function?
Forms stable covalent linkages, changing the charge and overall structure of the proteins, therefore affecting function.
What is HbA1c?
Glucose reacts with Hb to form glycated Hb.
How is HbA1c used clinically?
Percentage of Hb glycated is a good indicator of how effective glucose control has been.
What does HbA1c indicate?
The average blood glucose concentration over the preceding 2-3 months (RBC lifespan).
What percentage of Hb is glycated in normal healthy individuals?
4-6%
What macrovascular complications are associated with diabetes?
- Stroke risk
- MI risk
- Poor peripheral circulation - feet
What microvascular complications are associated with diabetes?
- Diabetic eye disease
- Diabetic nephropathy
- Diabetic neuropathy
- Diabetic feet
How does diabetes cause eye disease?
Retinopathy - damage to blood vessels in retina can lead to blindness
Glaucoma - osmotic effects of glucose can alter lens and cause visual problems
Cataracts
How does diabetes cause nephropathy?
Damage to glomeruli, poor blood supply due to changes in the kidney blood vessels, or damage from UTI’s which are more common in diabetics.
What is an early sign of nephropathy?
Increased protein in the urine - microalbuminuria
How does diabetes cause neuropathy?
Damage to peripheral nerves - loss/changes in sensation, alteration in function of ANS
What is diabetic feet?
Poor blood supply, damage to nerves and increased risk of infection make the feet vulnerable.
- Loss of feet through gangrene
What is metabolic syndrome?
The co-occurance of multiple CVD risk factors in the same individual.
Why are oral hyopglycaemic agents avoided in Type 1 diabetes?
Risk of hypoglycaemia
How can C peptide be used to differentiate between T1 and T2 diabetes?
Present in patients with T2 but absent in patients with T1
Which patients are at risk of spontaneous ketoacidosis?
Type 1
Why is metformin given to T2 diabetics?
Inhibits gluconeogenesis
Why are sulphonylureas given to T2 diabetics?
Binds directly to ATP sensitive K+ ATPase, causing it to close and triggering hyper polarisation and insulin release.
How does insulin deficiency lead to hyperglycaemia?
Glycogenolysis increases
Gluconeogenesis increases
Peripheral glucose uptake reduced
Briefly explain why insulin has to be injected and cannot be taken orally in pill form.
Insulin is a peptide hormone so would be broken down in the gastrointestinal tract to its consituent amino acids if it were to be taken orally.
Is the glycation of haemoglobin to form HbA1c catalysed by an enzyme?
No, glycation is non-enzymatic.
Name the two most significant factors underlying the aetiology of metabolic syndrome.
- Central obesity
2. Insulin resistance
Why is tiredness/weakness a symptom of T1 diabetes?
loss of muscle mass, dehydration
Outline the major ultrastructural features of the -cell that relate to the synthesis, storage and secretion of insulin
Many mitochondria – high energy requirement
Extensive RER
Extensive Golgi
Many storage vesicles
Many microtubules & microfilaments – active secretory tissue (exocytosis).
How does insulin lower blood glucose concentration?
Glucose uptake into muscle and adipose tissue
Stimulating glycogenesis in muscle and liver
Stimulating glucose oxidation in liver.
Stimulating lipogenesis in liver and adipose tissue.
Inhibits gluconeogenesis in liver.
What effect do catecholamines have on insulin secretion? Why is this beneficial?
Inhibit insulin secretion, enables a raise in blood glucose under stressful conditions
What effect do gut hormones have on insulin secretion?
Stimulate insulin secretion after a meal, so the digestion components can be absorbed quickly to avoid major increases in their concentration.
