T2 L10 Diabetes Flashcards
What is type 1 insulin-dependent diabetes?
Patients can’t survive without insulin
Mainly starts when young but can be observed in later life
Ketosis may lead to death
No feedback inhibition by insulin on alpha cells so glucagon levels remain high
Treatment is insulin injections
What is IDDM caused by?
Autoimmune destruction of beta cells of the islets of Langerhans
Sometimes follows a viral infection such as measles, mumps or rubella.
What are the symptoms of IDDM?
Thirst Tiredness Weight loss Polyuria Hyperglycaemic coma
Why does insulin deficiency cause weight loss, weakness & fatigue?
A low insulin:glucagon ratio Increased protein breakdown Increased plasma amino acid levels Loss of muscle mass Weight loss, weakness & fatigue
What happens to the liver in IDDM?
Liver remains gluconeogenic because of the high glucagon regardless of high blood glucose
Lactate & amino acids such as alanine from protein breakdown are the main substrates for glucose production which leads to muscle wasting.
Glycogen synthesis & glycolysis are inhibited so the liver can’t adequately buffer blood glucose.
Fatty acids from lipolysis enter the liver & provide energy to support gluconeogenesis. Excess fatty acids are converted to TAG & VLDL
Excess acetyl CoA from fatty acid oxidation is converted to ketone bodies
What happens if the ketone bodies from the liver aren’t used rapidly?
Accumulation of ketone bodies & H+ in the blood can lead to ketoacidosis
What happens to the muscle in IDDM?
Relatively little glucose entry into the muscle & peripheral tissue due to the lack of insulin - contributes to hyperglycaemia
Fatty acid & ketone body oxidation are the major source of fuel
Proteolysis occurs to provide carbon skeletons for gluconeogenesis which leads to muscle wasting.
What happens to the adipose tissue in IDDM?
Despite high glucose concentration in the plasma the uptake of glucose is diminished by the loss of insulin.
A low insulin : glucagon ratio enhances lipolysis & leads to continuous breakdown of TAG & release of fatty acids & glycerol into the bloodstream.
What happens to the plasma & urine in IDDM?
Constant production of excess glucose leads to hyperglycaemia
Glucose concentration exceeds renal threshold & is excreted into the urine - causes loss of water & thirst
Fatty acid synthesis is decreased - VLDL secreted by the liver & chylomicrons entering the gut can’t be properly metabolised due to the expression of lipoprotein lipase being regulated by insulin.
Results in hypertriglyceridaemia & hyperchylomicronaemia & susceptibility to CVD.
What are the short term consequences of diabetes?
Hyperglycaemia & ketoacidosis (type I diabetes)
Hyperosmolar hyperglycaemic state (type II diabetes)
What are the long term consequences of diabetes?
Predisposition to CVD & organ damage
Retinopathy - cataracts, glaucome & blindness
Nephropathy
Neuropathy
What does excess glucose result it?
Generation of ROS
Osmotic damage to cells
Glycosylation leading to alterations in protein function
Formation of advanced glycation end products which increase ROS & inflammatory proteins
What are the 2 major tests to diagnose diabetes?
Fasting blood glucose levels
Glucose tolerance test
Describing the fasting blood glucose levels test
Overnight fast
Blood glucose value of 126mg/dL & above on 2 separate occasions.
Normal ranges are 70-110mg/dL
Describe the glucose tolerance test
Performed in the morning after an overnight fast
Fasting blood sample is removed. Individual drinks glycols drink containing 75g of glucose.
Blood glucose is sampled at 20min, 1 hour & 2 hour
