Diabetes: Pathogenesis and Metabolic Abnormalities

Question 1

is insulin an anabolic or catabolic hormone

Answer 1

anabolic - storage hormone

Question 2

what effect does insulin have on fat and protein breakdown

Answer 2

it inhibits it

Question 3

what is the most predominant cell in the pancreatic islet

Answer 3

beta cells

Question 4

what do delta cells secrete

Answer 4

somatostatin (GHIH)

Question 5

describe the structure of the pancreatic islet

Answer 5

from outside in

exocrine acinus
layer or two of alpha cells
beta cells

delta cells dotted around

Question 6

what do F cells secrete

Answer 6

pancreatic polypeptide

Question 7

what is the structure of insulin

Answer 7

alpha and beta chains linked by a c peptide

Question 8

how is insulin secreted and what happens after secretion

Answer 8

secreted as a prohormone
b-cell peptidases cleave off c -peptide
this makes active insulin

Question 9

how is insulin secretion controlled

Answer 9

1. beta cells allow glucose in freely (through GLUT2 channels)
   this is allows glucose uptake to be proportional to levels in the blood
2. glucose is metabolised by the glucokinase enzyme
3. the ATP which is produced inhibits the opening of the K+ channel on the cell membrane
4. this results in an increase in K+ levels in the cell
5. this causes membrane depolarisation
6. this triggers Ca2+ channels to open
7. calcium influx triggers exocytosis of vesicles containing insulin

Question 10

why are there two peaks of insulin release

Answer 10

the first peak is the release of stored insulin from cells
the second peak is the newly synthesised insulin

Question 11

what is c-peptide useful for

Answer 11

it can be measured to show endogenous secretion of insulin in people with diabetes

Question 12

where does insulin go when it is secreted from the pancreas

Answer 12

secreted into portal vein
so acts on liver first
then passes into systemic circulation
then acts on muscle and fat

Question 13

where is glycogen stored

Answer 13

liver and muscle

Question 14

what effect does insulin have on amino acids uptake and protein synthesis

Answer 14

increases aa uptake and causes protein synthesis

Question 15

does insulin increase or decrease cell proliferation and apoptosis

Answer 15

increase proliferation
decrease apoptosis

Question 16

how does insulin work in cells

Answer 16

insulin binds to receptor
triggers complicated cascade
eventually this triggers GLUT4 vesicles to translocate to the surface
this allows glucose uptake

Question 17

what allows for insulin dependent glucose uptake into cells

Answer 17

GLUT4 only moves to membrane in response to insulin

Question 18

what four substances can be broken down into glucose

Answer 18

alanine
pyruvate
lactate
glycerol

Question 19

what hormones cause quick release of insulin

Answer 19

fight or flight hormone (e.g. cortiosl, adrenaline and noradenaline)

Question 20

name 3 severe insulin resistance syndromes

Answer 20

leprechaunism
rabson-mendenhall syndrome
type a insulin resistance

Question 21

is visceral or subcutaneous fat more metabolically active

Answer 21

visceral

Question 22

three hormonal disorders which cause insulin resistance and name what hormone is primarily effected

Answer 22

acromegaly (growth hormone)
pheochromocytomas (tumour of adrenal glands - adrenaline)
cushing’s disease (pituitary tumour)

Question 23

what fasting blood glucose levels are normal, prediabetic and diabetic

Answer 23

<6 - normal
6-7 - prediabetic
>7 - diabetic

Question 24

what fasting blood glucose levels make macro and microvascular complications more likely

Answer 24

macro - >6mmol/l
micro - >7mmol/l

Question 25

what tests can be used to diagnose diabetes

Answer 25

fasting plasma glucose

2h glucose tolerance test
random plasma glucose

HbA1c

Question 26

diabetes diagnosis

Answer 26

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

Question 27

what is required for diabetes diagnosis is a patient is asymptomatic

Answer 27

repetition of the same test

Question 28

if someone has a random plasma glucose of <11.1mmol/l are they diabetic

Answer 28

they could be - it depends on when they’ve eaten

Question 29

what is HbA1c

Answer 29

glycated haemoglobin

Question 30

why is HbA1c useful (3 points)

Answer 30

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

Question 31

what HbA1c is normal

Answer 31

<41mmol/mol

Question 32

when should HbA1c not be used

Answer 32

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

Question 33

how does HbA1c change in pregnancy

Answer 33

it is lower

Question 34

what does HbA1c allow monitoring of

Answer 34

efficacy of treatment
adherence to treatment
risk of developing complications

Question 35

describe glucose tolerance test

Answer 35

fast overnight
in morning given 75g glucose orally
plasma glucose measured at 0h and 2h

Question 36

what is impaired glucose tolerance

Answer 36

fasting plasma glucose <7mmol/l
plasma 2h after GTT 7.8-11mmol/l

Question 37

prognosis for impaired glucose tolerance

Answer 37

15% develop diabetes in 5 years
15% return to normal
increased risk of CVD death

Question 38

how is impaired glucose tolerance managed

Answer 38

annual monitoring of glucose tolerance

Question 39

what is impaired fating glucose

Answer 39

fasting plasma glucose >6mmol/l but <6.9mmol/l

Question 40

is impaired glucose tolerance always associated with impaired fasting glucose

Answer 40

not always but often

Question 41

definition of pre-diabetic state

Answer 41

fasting blood glucose - 6-6.9
HbA1c - 42-47
OGTT after 2h - 7.8-11