diabetes mellitus Flashcards
1
Q
what is type 1 diabetes mellitus? 6
A
- patients who lack insulin
- treatment= insulin injections
- juvenile onset
- results from autoimmune destruction of the beta cells of the islets of langerhans
- sometimes follows viral infection such as mumps, rubella or measles
- as there is no feedback inhibition by insulin on alpha cells, glucagon levels remain high, therefore also a disease of glucagon excess
2
Q
what are the metabolic consequences of type 1 diabetes? 4
A
- blood insulin levels are low despite high blood glucose. whereas glucagon levels are raised
- insulin: glucagon ratio cannot increase even when dietary glucose enters from the gut
- metabolism is stuck in the starved phase
- low insulin: glucagon ration leads to the induction of catabolic enzymes and repression of anabolic enzymes
3
Q
describe the type 1 diabetic state? 5
A
- despite high blood glucose, the liver remains gluconeogenic because of high glucagon
- lactate and amino acids such as alanine from protein breakdown are the main substances for glucose production which causes muscle wasting
- glycogen synthesis and glycolysis are also inhibited; therefore, the liver cannot adequately buffer blood glucose
- fatty acids from lipolysis enter the liver and provide energy to support gluconeogenesis while in excess fatty acids are converted to TAGs and VLDL
- excess acetyl CoA from fatty acid oxidation converted to ketone bodies and if not used sufficiently can lead to ketoacidosis due to the accumulation of ketone bodies and H+ ions in the blood
4
Q
what are ketone bodies? 3
A
- occurs normally under all conditions but increases dramatically during starvation
- prolonged low insulin: glucagon ratio results in:
- increased metabolism of fatty acids from the adipose tissue
- increased amounts of the enzymes required to synthesise and utilise ketone bodies
5
Q
why does lipid mobilisation stimulate ketone body formation? 3
A
- in the liver, the increased demand for gluconeogenesis results in the depletion of oxaloaxcetate
- this decreases the capacity of the TCA cycle which increases the levels of acetyl-CoA present
- acetyl-CoA is the substrate for the production of ketone bodies
6
Q
how are ketone formed? 2
A
- condensation of 2 molecules of acetyl-CoA (catalysed by thiolase)
- acetoacetate and D-beta-hydroxybutryrate can be converted back to acetyl-CoA in peripheral tissues for use in the TCA cycle
7
Q
describe the type 1 diabetic state in the muscle? 3
A
- relatively little glucose entry into muscle and peripheral tissues because of insulin lack. this contributes to hyperglycaemia
- fatty acids and ketone body oxidation used as the major source for fuel
- proteolysis occurs to provide carbon skeletons for gluconeogenesis leading to muscle wasting
8
Q
describe the type 1 diabetic state of adipose tissue? 2
A
- despite the high glucose concentrations in the plasma, uptake of glucose is diminished by loss of insulin
- low insulin:glucagon ratio enhances lipolysis leading to the continuous breakdown of tricylglycerol and release of fatty acids and glycerol into the bloodstream to support energy production in the peripheral tissues and gluconeogenesis in the liver
9
Q
describe the type 1 diabetic state of plasma and urine? 4
A
- constant production of excess glucose while utilising less leads to hyperglycaemia
- glucose concentration exceeds the renal threshold and is excreted in the urine (glycosuria) with loss of water and development of thirst
- fatty acids synthesis greatly diminished in the diabetic state; VLDL is secreted by the liver and chylomicrons entering from the gut cannot be metabolism properly as the expression of lipoprotein lipase is regulated by insulin
- this results in hypertriglyceridemia and hyperchylomicroaemia and susceptibility to cardiovascular events
10
Q
what are the short term life threatening consequences diabetes? 2
A
- hyperglycaemia and ketoacidosis (type 1)
- hyperosmolar hyperglycaemia state (non-ketotic hyperosmolar coma ) (type 2)
11
Q
what are the long term life threatening consequences of diabetes? 4
A
- predisposition to CV disease and organ damage
- retinopathy- cataracts, glaucoma, blindness
- nephropathy
- neuropathy
12
Q
what does a high blood concentration of glucose result in? 4
A
- generation of ROS
- osmotic damage to cells
- glycosylation leading to alterations in protein function
- formation of advanced glycation end products (AGE) which increases ROS and inflammatory proteins
13
Q
what are the two major tests for diagnosing diabetes?
A
- Fasting blood glucose levels:
- After an overnight fast, a blood glucose level of 126mg/dl and above on at least 2 occasions indicates diabetes
- Glucose tolerance test:
- Performed in the morning after an overnight fast
- Fasting blood sample is removed and subject drinks a glucola drink containing 75g of glucose. Blood glucose is then samples at 20min, 1hr and 2hr
14
Q
describe HbA1c- glycated haemoglobin? 2
A
- Lifespan of RBCs is 8-12 weeks so HbA1c measurements can be used to reflect average blood glucose levels over that duration, providing a useful longer-term gauge for blood glucose control
- Target for diabetics= 44mmol/mol
15
Q
how do we treat type 1 diabetes? 2
A
- mimic daily insulin secretion
- endogenous insulin secretion normally peaks within one hour after a meal with insulin secretion and plasma glucose levels returning to basal levels within two hours of the end of the meal induced hyperglycaemia
