Diabetes: Pathogenesis and Metabolic Abnormalities Flashcards
is insulin an anabolic or catabolic hormone
anabolic - storage hormone
what effect does insulin have on fat and protein breakdown
it inhibits it
what is the most predominant cell in the pancreatic islet
beta cells
what do delta cells secrete
somatostatin (GHIH)
describe the structure of the pancreatic islet
from outside in
exocrine acinus
layer or two of alpha cells
beta cells
delta cells dotted around
what do F cells secrete
pancreatic polypeptide
what is the structure of insulin
alpha and beta chains linked by a c peptide
how is insulin secreted and what happens after secretion
secreted as a prohormone
b-cell peptidases cleave off c -peptide
this makes active insulin
how is insulin secretion controlled
- beta cells allow glucose in freely (through GLUT2 channels)
this is allows glucose uptake to be proportional to levels in the blood - glucose is metabolised by the glucokinase enzyme
- the ATP which is produced inhibits the opening of the K+ channel on the cell membrane
- this results in an increase in K+ levels in the cell
- this causes membrane depolarisation
- this triggers Ca2+ channels to open
- calcium influx triggers exocytosis of vesicles containing insulin
why are there two peaks of insulin release
the first peak is the release of stored insulin from cells
the second peak is the newly synthesised insulin
what is c-peptide useful for
it can be measured to show endogenous secretion of insulin in people with diabetes
where does insulin go when it is secreted from the pancreas
secreted into portal vein
so acts on liver first
then passes into systemic circulation
then acts on muscle and fat
where is glycogen stored
liver and muscle
what effect does insulin have on amino acids uptake and protein synthesis
increases aa uptake and causes protein synthesis
does insulin increase or decrease cell proliferation and apoptosis
increase proliferation
decrease apoptosis
how does insulin work in cells
insulin binds to receptor
triggers complicated cascade
eventually this triggers GLUT4 vesicles to translocate to the surface
this allows glucose uptake
what allows for insulin dependent glucose uptake into cells
GLUT4 only moves to membrane in response to insulin
what four substances can be broken down into glucose
alanine
pyruvate
lactate
glycerol
what hormones cause quick release of insulin
fight or flight hormone (e.g. cortiosl, adrenaline and noradenaline)
name 3 severe insulin resistance syndromes
leprechaunism
rabson-mendenhall syndrome
type a insulin resistance
is visceral or subcutaneous fat more metabolically active
visceral
three hormonal disorders which cause insulin resistance and name what hormone is primarily effected
acromegaly (growth hormone)
pheochromocytomas (tumour of adrenal glands - adrenaline)
cushing’s disease (pituitary tumour)
what fasting blood glucose levels are normal, prediabetic and diabetic
<6 - normal
6-7 - prediabetic
>7 - diabetic
what fasting blood glucose levels make macro and microvascular complications more likely
macro - >6mmol/l
micro - >7mmol/l
what tests can be used to diagnose diabetes
fasting plasma glucose
2h glucose tolerance test
random plasma glucose
HbA1c
diabetes diagnosis
any of the following
fasting plasma glucose >7.0mmol/l
2h plasma glucose in OGTT >11.1mmol/l
random plasma glucose >11.1 mmol/l
HbA1c > 48 mmol/mol
what is required for diabetes diagnosis is a patient is asymptomatic
repetition of the same test
if someone has a random plasma glucose of <11.1mmol/l are they diabetic
they could be - it depends on when they’ve eaten
what is HbA1c
glycated haemoglobin
why is HbA1c useful (3 points)
it is formed at a directly proportional rate to the blood glucose concentration
it reflects blood glucose concentration during the 120 days of the erythrocyte
blood sample can be taken any time of day and is not affected by food consumption
what HbA1c is normal
<41mmol/mol
when should HbA1c not be used
rapid onset of diabetes (e.g. suspected type 1)
pregnancy
conditions where red blood cell survival may be reduced or increased
renal dialysis
iron and vitamin B12 deficiency
how does HbA1c change in pregnancy
it is lower
what does HbA1c allow monitoring of
efficacy of treatment
adherence to treatment
risk of developing complications
describe glucose tolerance test
fast overnight
in morning given 75g glucose orally
plasma glucose measured at 0h and 2h
what is impaired glucose tolerance
fasting plasma glucose <7mmol/l
plasma 2h after GTT 7.8-11mmol/l
prognosis for impaired glucose tolerance
15% develop diabetes in 5 years
15% return to normal
increased risk of CVD death
how is impaired glucose tolerance managed
annual monitoring of glucose tolerance
what is impaired fating glucose
fasting plasma glucose >6mmol/l but <6.9mmol/l
is impaired glucose tolerance always associated with impaired fasting glucose
not always but often
definition of pre-diabetic state
fasting blood glucose - 6-6.9
HbA1c - 42-47
OGTT after 2h - 7.8-11
