diabetes Flashcards
which 2 tissues does insulin act on via GLUT-4?
striated skeletal muscle (including heart)
adipose tissue
how does glucose transport occur?
facilitated diffusion via glucose transporters
cell membrane is impermeable to glucose
what effect does insulin have on processes in the liver?
increased glucose uptake, glycogenesis
decreased glycogenolysis, gluconeogenesis, lipolysis
what effect does insulin have on processes in the fat?
increased glucose uptake, lipogenesis
decreased lipolysis
what effect does insulin have on processes in the muscle?
increased glucose uptake, glycogenesis, protein synthesis
decreased protein catabolism
what is the difference between GLUT-4 and other glucose transporters and why is this relevant?
GLUT-4 is insulin regulated
GLUT-1 - 3 are insulin independent
if excess glucose is present in the blood and insulin is not responding properly then tissues supplied by GLUT 1-3 will still take up some glucose
what is the overall effect of insulin resistance and T2DM on liver, fat and muscle tissues?
increased blood glucose (hyperglycaemia)
free fatty acids
(theoretically more amino acids since less protein synthesis)
describe the glucose metabolism pathway to produce ATP.
glucose enters cell via GLUT-4 (insulin regulated) from bloodstream
glucose to pyruvate (glycolysis)
pyruvate to acetyl CoA (link reaction)
acetyl CoA undergoes TCA cycle (Krebs) to produce 30 molecules of ATP per glucose molecule
what happens in T2DM (in terms of insulin)?
insulin resistance
insufficient insulin produced to a degree, maybe in later stages
what is the body’s initial reaction to insulin resistance?
increased production of insulin to try and counteract
eventually β cells cannot produce enough insulin to meet requirements caused
what are the 2 main pathophysiological problems in T2DM?
insulin resistance
impaired β cell function
what causes increased risk of diabetes?
diabetes susceptibility genes (family history)
visceral fat especially resistant to insulin
diet
adipokines
- generally upregulate and downregulate insulin, adipose cells in obese people are dysfunctional and adipokines that reduce insulin sensitivity
- reduce insulin sensitivity by causing hyperplasia and hypertrophy in β cells
- amyloid clogs β cells and leads to hypertrophy
ethnicity (south Asian, African Caribbean)
sex
age
what are the symptoms of diabetes?
thirst
unintended weight loss
increased urination
what is impaired fasting glucose?
predominantly hepatic insulin resistance leads to continuous glucose output from the liver
what is impaired glucose tolerance?
predominantly muscle insulin resistance plus impaired post prandial insulin release results in poor cellular glucose uptake
what is pre diabetes?
impaired fasting glucose AND impaired glucose tolerance
state of impaired glucose metabolism that doesn’t quite meet diabetes criteria
what is HbA1C? how can it be used to diagnose and monitor diabetes?
glycosylated haemoglobin
non enzymatic process to form, can occur with monosaccharides glucose, fructose and galactose (glucose less easily)
formation of HbA1C occurs proportionately to plasma glucose levels
what are the advantages of an HbA1C test?
no need to fast and take a sugary drink beforehand (no prep - blood glucose taken 2 hours after 75g oral glucose load)
RBC life span is around 120 days therefore results show glucose levels over 3 months
what are the disadvantages of an HbA1C test?
if RBCs die young results will be falsely low
co morbidity may interfere with the test
- pregnancy
- advanced kidney disease
- anaemia
what are the fasting ranges of glucose in normal metabolism?
<5.5 mmol/L
what are the ranges of post prandial glucose in both normal metabolism and impaired fasting glucose?
<7.8 mmol/L
what is the range in a random test in normal metabolism, impaired fasting glucose and impaired glucose tolerance?
<11.1 mmol/L
what are the impaired fasting glucose ranges for fasting glucose?
5.5 - 6.9 mmol/L
what are the impaired glucose tolerance fasting glucose ranges?
<7 mmol/L
