Diabetes: pancreas physiology and disease Flashcards
1
Q
is insulin an anabolic or catabolic hormone?
A
anabolic
2
Q
what does an anabolic hormone do?
A
it promotes the storage and synthesis of products
3
Q
how does insulin increase glucose absorption?
A
- it binds to receptors which trigger GLUT4 receptors to move from cytoplasm to cell membrane, allowing more glucose in the cell
4
Q
where is insulin produced, and by which cells?
A
beta cells in Islets of Langerhans, in the pancreas
5
Q
what class of hormone is insulin?
A
peptide hormone
6
Q
what are the properties of peptide hormones?
A
- can be stored in vesicles
- bind to membrane receptors
- water soluble
- short half-life
7
Q
which cellular steps occur for the release of insulin into the circulation?
A
- glucose binds to GLUT receptors on Beta cells
- metabolism increased, more ATP/K+ activity
- intracellular K+ rises and cell depolarises
- Ca2+ channels open and it flows into the cell
- vesicles merge with cell membrane and insulin flows out
8
Q
which hormones act as counter-regulatory mechanisms to insulin?
A
- glucagon
- adrenaline
- cortisol
- growth hormone
9
Q
list some of the actions of insulin
A
- increased glucose uptake through GLUT4 receptors
- increased glycogenesis/reduced glycogenolysis
- increased lipogenesis/reduced lypolysis
- increased protein synthesis/reduced gluconeogenesis
- increased K+ uptake into cells
10
Q
what stimuli trigger insulin release?
A
- high blood glucose
- amino acids in blood
- glucagon in blood
- vagus nerve stimulation
- incretin hormones acting on GI secretion/motility
11
Q
where is excess glucose stored in the body, and in what form?
A
- stored in muscle and liver as glycogen
- stored in liver and adipose tissue as TAG
12
Q
what is the term for the time period after meals during which insulin is most active?
A
Absorptive state
13
Q
which two tissues in the body are insulin-dependent?
A
muscle and adipose tissue
14
Q
what are the normal glucose levels in the blood?
A
around 5.5mM
15
Q
which specific glucose transporters are found in which body tissues?
A
GLUT 1 and 3 - kidneys, brain, RBC
GLUT 2 - liver, beta cells in pancreas
GLUT 4 - muscle and adipose tissue
16
Q
how does insulin act on liver cells?
A
- insulin binding to liver cell activates hexokinase, which causes glucose in the cell to be phosphorylated to G6P, trapping it in the liver cell and causing more glucose to flow in down concentration gradient
17
Q
why are insulin levels associated with hypo or hyperkalaemia?
A
- because insulin stimulates Na/K+ase pump, drawing more K+ into cells
18
Q
what kind of receptors does insulin bind to on the cell membrane?
A
tyrosine kinase receptors
19
Q
what reduces the secretion of insulin?
A
- low blood glucose
- somatostatin
- stress (eg hypoxia)
- sympathetic stimulation
20
Q
what class of hormone is glucagon?
A
a peptide hormone
21
Q
where is glucagon produced?
A
in alpha cells in pancreatic Islet of Langerhans cells
22
Q
what is the main purpose of glucagon?
A
to mobilise glucose into the circulation
23
Q
what are the actions of glucagon?
A
- increase gluconeogenesis
- increase lypolysis
- increase glycogenolysis
- increase ketogenesis
24
Q
on what kinds of receptors does glucagon act?
A
G-protein coupled receptors
25
on which cells do most of the actions of glucagon have effect?
liver cells
26
what effect do amino acids in the blood have on insulin and glucagon?
raise levels of insulin AND glucagon
27
what effect do high blood glucose levels have on insulin and glucagon?
high blood glucose - increase insulin and reduce glucagon
28
what effect do low blood glucose levels have on insulin and glucagon?
low blood glucose - reduce insulin and increase glucagon
29
what is thought to be the aetiology of diabetes type 1?
genetic predisposition
environmental triggers
autoimmunity
30
what is the pathology behind diabetes type 1?
lack of insulin secretion due to autoimmune destruction of islets of langerhans
31
which family member of a type 1 diabetic patient is most likely to also develop the disease?
an identical twin
32
which type of diabetes is most common worldwide?
type 2 diabetes
33
how do obesity and genetics possibly lead to DM2?
- obesity causes strain on adipocytes, which therefore release FFA. increase in FFA = reduced insulin sensitivity
- if genes aren't present that allow higher insulin amounts to be secreted to compensate, this leads to hyperglycaemia and DM2
34
how does diabetes affect the large arteries?
glucose binding to endothelium can precipitate atherosclerosis
35
how does diabetes affect arterioles and capillaries?
through glycosylation:
- plasma proteins get trapped under endothelium
- collagen is crosslinked by glucose and harder to remove
36
which version of MODY has a higher likelihood to develop complications?
MODY due to mutations in transcription factors
37
list some of the symptoms for diabetic ketoacidosis
```
nausea and vomiting
drowsiness
abdominal pain
ketones on breath
kussmaul breathing
coma
```
38
what are the 4 T's for diabetes diagnosis?
thirst
thinner
toilet
tired
39
what investigation should be done immediately when suspecting DKA and undiagnosed diabetes?
random blood glucose + ketones
40
what determines the speed of absorption of insulin once injected?
whether it aggregates into hexamers once it's injected
41
what is the difference in action between slow acting and fast acting insulin injections?
slow insulin aggregates in hexamers and needs to be broken down into monomers before it can enter the circulation
fast insulin doesn't form hexamers and is taken up by bloodstream faster
42
how much is one unit of insulin equivalent to in carbohydrates?
10g of carbohydrate
43
what should a diabetes patient with the flu do if they notice rising ketones in blood?
- drink water
- give correction dose insulin
- contact team
44
what is the level of blood ketones at which a diabetic patient should seek urgent medical attention?
>3mmol/mol
45
what level of blood glucose is classed as hypoglycaemia?
<4mmol/mol
46
list some symptoms associated with hypoglycaemia
```
sweating
palpitations
shaking
hunger
drowsiness
odd behaviour
incoordination
speech difficulties
headache
nausea
```
47
what may contribute to a lack of awareness of hypoglycaemia?
- overly tight glycaemic control
- common episodes of hypo's
- loss of sweating/tremor
- longstanding disease
- age (young or old)
- reduced cognitive ability
48
how is hypoglycaemia managed?
by administering 15-20g glucose
49
what investigations should be done if a patient presents with DKA?
```
bloods - FBC, U&E, glucose
blood and urine glucose + ketones
blood and urine culture
blood gas
ECG
CXR
```
50
name some complications of DKA
```
hyperkalaemia/hypokalaemia
hypoglycaemia
cerebral oedema
acute kidney injury
ARDS
aspiration pneumonia
thromboembolism
```
51
what is the mechanism of action of metformin? where does it act?
increases insulin sensitivity at liver and muscle
52
how do sulfonyureas increase insulin secretion?
by blocking potassium channels, causing cell depolarisation and exocitosis of insulin vesicles
53
list some side effects of metformin
```
nausea
diarrhoea
lactic acidosis
renal/hepatic failure
GI upset
vit b12 deficiency
```
54
list some side effects of sulfonyureas
hypoglycaemia
weight gain
renal/hepatic failure
55
list some side effects of glitazones
weight gain
fluid retention
risk of fractures
risk of bladder cancer
56
list the side effects shared by DPP4 inhibitors and GLP-1 analogues
increased risk of pancreatic ca/infection
| nausea/vomiting
57
which drugs for T2DM are contraindicated in pregnancy?
sulfonyureas
GLP-1 analogues
DPP4 antagonists
SGLT-2 antagonists
58
what is the mechanism of action of sulfonyureas? where do they act?
increase insulin secretion in pancreatic islets
59
what is the mechanism of action of glitazones? where do they act?
increase insulin sensitivity in liver, muscle and adipose tissue
60
what is the mechanism of action of DPP4 inhibitors? where do they act?
inhibit incretin breakdown, increasing its action on pancreas
61
what is the mechanism of action of GLP-1 analogues? where do they act?
mimic the action of incretin on the pancreas, increasing its effect because analogues are not broken down as quickly as incretin itself
62
out of the T2DM drugs, which ones are injectable?
GLP-1 analogues
| insulin
63
what is the mechanism of action of SGLT-2 antagonists? where do they act?
reduce glucose reabsorption in proximal convoluted tubule of nephrons
64
list some side effects of SGLT-2 antagonists
```
dehydration
hypotension
kidney damage
UTIs
risk of DKA
```
65
which type of insulin is normally indicated in patients with T2DM?
intermediate acting - once daily
66
what is the range of HbA1c that should be achieved for patients with T2DM
between 48 and 58mmol/mol
67
what determines whether metformin or sulfonyureas are used as 1st line treatment for T2DM? justify your answer
presence of symptoms.
metformin takes longer to stabilise, use if asymptomatic
sulfonylureas act quicker, use if symptomatic
68
what are the 5 concepts of T2DM treatment?
1. set HbA1c target
2. Take 5 - assess/treat other risk factors first
3. optimise current treatment
4. choose glucose lowering drug
5. set review date for HbA1c
69
what are the 5 risk factors to assess and treat prior to changing T2DM medication?
```
smoking
obesity
blood pressure
sedentary lifestyle
diet
```
70
how does diabetic neuropathy contribute to hypoglycaemia?
loss of autonomic regulation to counteract low blood glucose
71
what is the first sign of diabetic nephropathy?
microalbuminuria
72
list some signs of diabetic retinopathy that can be see in the back of the eye
microaneurysms (dots)
microhaemorrhages (blots)
cotton wool spots (infarcts)
lipid deposits (hard exudates)
73
what is a common consequence of diabetic neuropathy and peripheral vascular disease?
loss of sensation in foot and ulcer development
74
how is diabetic retinopathy managed?
with laser photocoagulation
75
how is diabetic nephropathy managed?
with blood pressure control
76
how is diabetic neuropathy managed?
foot care and antibiotics for osteomyelitis
77
how do fatty foods affect glucose absorption?
they slow down glucose absorption
78
what are the guidelines on diabetes and diet?
healthy and balanced diet
| plenty of fluids
79
what are the guidelines on diabetes and alcohol?
national guidelines, but more than 2-3 units at one time can cause hypos
80
what are the guidelines on diabetes and driving?
have to inform DVLA if on insulin
can drive HGV under strict medical surveillance
check BG two hours before long car journeys, every 2 hours during journey
have CHO in car
81
what are the guidelines on diabetes and travel?
always carry insulin with you
try to avoid gastroenteritis
adjust insulin with time differences
82
what are the guidelines on diabetes and exercise?
encourage exercise
reduce insulin before and after exercise to reduce risk of hypos
eat more CHO to match exercise
plenty of fluids
83
what are the guidelines on diabetes and work?
armed forces not possible
| oil workers/blue light drivers in some circumstances
