Metabolism S8 - Diabetes Flashcards
Describe diabetes mellitus
A heterogenous group of multifactorial, polygenic syndromes characterised by chronic hyperglycaemia due to insulin deficiency, insulin resistance or both
How does ketoacidosis develop in a person with Type I diabetes?
- Acetyl CoA is at high concentrations due to increased fatty acid oxidation as glucose cannot be taken up by cells
- Noradrnaline, a stress hormone, is released stimulating hormone sensitive lipase to begin lipolysis
- Lack of insulin means that the enzyme lyase is no longer inhibited ao acidic ketone bodies are synthesised from the already high levels of Acetyl CoA
- Ketoacidosis occurs as concentration of ketone bodies exceeds buffering capacity
What is the typical presentation of a person with type I diabetes?
- Genetic markers (HLA DR3 & DR4) and auto-antibodies detected
- Impaired glucose tolerance
- Development of diabetes
- Total insulin dependence
What is the typical presentation of a person with type II diabetes?
- Insulin resistance
- Impaired glucose tolerance
- Diabetes
- Eventually become totally insulin dependant
What is Hba1c? Why is it used?
- Glycated haemoglobin
- Produced when glucose in blood reacts with a terminal valine
- A good marker of how well diabetes is being manages (120 days circulation of RBCs)
- Above 6.5 indicates poorly managed diabetes
List metabolic, microvascular and macrovascular long term side effects of diabetes
Metabolic - Polyuria, polydipsia
Microvascular - Retinopathy, neuropathy, nephropathy
Macrovascular - increased risk of stroke, myocardial infarction, poor circulation to the periphery
How is retinopathy caused in diabetic patients?
- Excess glucose is converted to sorbitol by aldose reductase
- This depletes NADPH reserves leading to increased disulphide bond formation whilst the accumulation of sorbitol causes osmotic damage to cells
Describe the structure of beta cells
- ATP sensitive potassium channels
- Voltage gated calcium channel
- GLUT 2 receptor
- Insulin secretory granules
- Large amounts of RER and golgi for insulin production
What stimulates insulin production?
- Glucose at high concentrations is transported into beta cells through GLUT 2 receptors by facilitated diffusion
- Glucose metabolised to ATP
- ATP blocks ATP sensitive potassium channels
- Prevents potassium moving out leading to depolarisation of the membrane
- Voltage gated calcium ion channels open and calcium ions move in to beta cells
- Stimulates release of insulin secretory granules by exocytosis
How can diabetes be diagnosed?
Triad of symptoms - Polyuria, polydipsia, unexplained weight loss
- Random venous plasma glucose concentration above 11.1mmol/l
- Fasting plasma glucose concentrations above 7 mol/L
- Plasma glucose concentration above 11.1mmol/L two hours after 75g anhydrous glucose in oral glucose tolerance test
TWO must be used to confirm diabetes if no symptoms present
How does polyuria occur?
- Glucose normally reabsorbed from blood at the proximal tubule with water following it
- The reabsorption here is isosmotic
- In diabetes mellitus, large quantities of glucose are filtered by the kidney and not all of it can be reabsorbed
- The extra glucose remains in the nephron tube
- This places an extra osmotic load on the nephron, and means less water is reabsorbed to maintain the isosmotic nature
What are the features of keto-acidosis?
Prostration, hyperventilation, nausea, vomiting, dehydration and abdominal pain
What symptoms do type I sufferers suffer from?
Triad of symptoms:
1) Polyuria
2) Polydipsia
3) Unexplained weight loss
What symptoms do type II sufferers suffer from?
- Triad of symptoms
- Lack of energy
- Persistent infections
- Slow healing of minor skin damage
- Visual problems
What is hypoglycaemia and what are its consequences?
- Blood glucose concentration less than 3mmol/L
- Acute effects include sweating, slurred speech, trembling, palpitations, headache, sickness and staggering
- Can rapidly lead to unconsciousness and death if untreated as CNS starved of oxygen
