11. Effects of Acute and Chronic Hyperglycaemia Flashcards
What are normal glucose levels before meals?
4-5.9 mmol/L
What are normal glucose levels 2hr after meals?
Under 7.8mmol/L
What glucose levels are considered diabetic in a fasting state?
> 7.1mmol/L
What glucose levels are considered diabetic 2 hrs after a meal?
> 11.1mmol/L
What are the symptoms of acute hyperglycaemia?
Glycosuria
Dehydrating osmotic diuresis (polyuria, polydipsia, hypokalemia, hyponatraemia)
Polyphagia (increased appetite)
Metabolism of protein and fat (weight loss and protein deficiency)
What is a resulting marker for an episode of acute hyperglycaemia?
Leave increased HbA1c
What hormones cause a change from glucose to lipid metabolism in diabetic ketoacidosis?
Glucagon, catecholamines, cortisol, GH
What exasperates hyperglycaemia in diabetic ketoacidosis?
Free fatty acids and AAs from lipolysis and proteolysis are used to increase gluconeogenesis
Why does ketogenesis increase in diabetic ketoacidosis?
Increase in free FAs which are broken down to produce ketones
Acetone produced a sweet smell on the breath
What are the symptoms of DKA?
Dehydration Fruity smelling breath Increased respiration (increased blood acidity) Nausea and vomiting Abdominal pain Lethargy, coma, shock
What is needed to diagnose DKA?
Hyperglycaemia, >11mM
Ketonaemia
Acidaemia, pH <7.3, anion gap> 12mmol/L
What is the treatment for DKA?
IV fluid replacement
IV insulin
K+ replacement
What is microvascular damage caused by?
Prolonged hyperglycaemia produces Advanced Glycation End Products
How do AGEs affect protein function?
Denaturation and functional decline
Alter enzyme activity
Interfere with receptor recognition
Organopathy (accumulation in tissue)
What happens when AGEs interact with RAGEs?
Alter gene expression
Induce pro-inflammatory status
What is non-proliferative diabetic retinopathy?
Caused by AGE build up
Micro-aneurysms
Haemorrhages
Exudates (lipoprotein leaks from vessels)
What is proliferative diabetic retinopathy?
Development of new blood vessels
Debilitating loss of vision
More haemorrhages
Local ischaemia triggers transcription factors eg. Hypoxia-inducible factor (HIF)
HIF expression induces the formation of new blood vessels
What are the symptoms of diabetic retinopathy?
Discoloured spots Blurred vision Vision blocked by patches or streaks Decreased night vision Sudden vision loss
What is peripheral diabetic neuropathy characterised by?
Numbness in toes, feet, fingers, arms Burning and pain Loss of sensation Decreased circulation Ulcer and gangrene leading to amputation
What is autonomic diabetic neuropathy characterised by?
Damage of nerves involved in regulation of BP, cardiac function, respiration, GIT, urinary systems
Gastroparesis (unable to empty stomach), diarrhoea, constipation, weight loss
Erectile disfunction
Incontinence
No chest pain during MI
What is diabetic nephropathy?
Thickening of glomerulus and basement membrane Microalbuminaemia Increased destruction of glomeruli Albumin in urine Chronic kidney failure
What is the treatment of diabetic nephropathy?
ACE inhibitors
AT receptor blockers
Dialysis and transplant
What results from diabetic macrovascular disease?
Heart disease, stroke, peripheral vascular disease
What effects does hyperglycaemia have on macrovascular disease?
Damages vascular endothelium
Increased platelet aggregation
Decreased thrombolysis
Promotes inflammatory responses
