Type 2 Diabetes Flashcards
(81 cards)
1
Q
What age range do T2DM patients present?
A
Middle age +
2
Q
What is the BMI range in T2DM patients?
A
Normal-high (25+)
3
Q
What history of autoimmune disease do T2DM patients have?
A
No history usually
4
Q
Is there family history link with T2DM?
A
Yes, often have FHx
5
Q
What will ketones appear as on T2DM urinalysis?
A
0 to +
6
Q
Is HbA1c helpful at presentation?
A
No
7
Q
What are the glucose levels at presentation?
A
10-25
8
Q
How does T2DM present acutely?
A
Hyperglycaemic Hyperosmolar Syndrome
9
Q
What are the C-peptide levels at presentation?
A
normal-raised
10
Q
Are C-peptides present at 5 years post diagnosis?
A
Yes
11
Q
Do T2DM patients present with complications? If so, how many?
A
Yes, 30%
12
Q
What is the definition of T2DM?
A
Insulin resistance with relative insulin deficiency
13
Q
How can obesity cause insulin resistance?
A
Obesity + lack of activity
Adiposity (inc FFAs, inc Adipokines)
Insulin resistance
14
Q
How can obesity lead to relative insulin deficiency?
A
Obesisty + lack of activity
Adiposity (inc FFAs, inc Adipokines)
Lipotoxicity
Vulnerable beta cells (genetics) can’t respond and produce more insulin
15
Q
How do normal beta cells respond to obesity?
A
Compensatory increase in insulin production
Euglycaemia
16
Q
Why is T2DM a progressive disease?
A
Beta cells deteriorate
No change in insulin sensitivity
17
Q
What symptoms do T2DM patients present with?
A
Polyuria Polydipsia Blurred vision Tiredness Recurrent UTIs
18
Q
What is the typical underlying cause of HHS?
A
undiagnosed T2DM
T2DM treated with diet only
19
Q
What can trigger HHS?
A
CVS event (MI/Stroke) Steroid therapy Sepsis Diuretics High refined sugar intake
20
Q
What is the aetiology in HHS?
A
Older patient
T2DM
If young then non white
21
Q
What can precipitate HHS and why?
A
Frequent infection
Stress hormone release
(eg glucagon -> inc blood sugar)
22
Q
What is the median glucose in HHS?
A
60
23
Q
What will renal function be in HHS?
A
significant impairment
24
Q
How is Na+ affected in HHS?
A
Often raised
25
How is osmolality affected in HHS? To what value? Why?
Often raised
Around 400
Hyperglycaemia/Hypernatraemia (ie concentrated blood)
26
What are the biochemical differences in HHS and DKA?
HHS is less ketonaemic/acidotic
27
How do you treat HHS compared to DKA? Why?
Fluids: more slowly in HHS(risk cerebral oedema)
Insulin: more slowly in HHS (more sensitive)
Na+: avoid rapid fluctuations (0.45%saline maybe)
LMWH for all unless contraindicated
28
What conditions are associated with insulin resistance syndrome?
Hypertension
Hyperlipidaemia
Hyperglycaemia
29
How is metabolic syndrome defined?
```
Insulin resistance syndrome OR T2DM
With 2+ :
Microalbuminuria
BMI >30
Dislipidaemia (TG>1.7, HDL<1.0)
```
30
What are the aims of treatment in diabetes?
```
Manage hyperglycaemia symptoms
Improve glycaemic control
Minimise weight gain
Help with weight loss
Reduce Micro/Macro complications
```
31
What is the first line treatment of T2DM?
Metformin
32
What of drug is metformin?
biguinide
| insulin sensitizer
33
What is the action of metformin?
Reduces hepatic gluconeogenesis by stimulating AMPK
Increasing glucose uptake and utilization in skeletal muscle
Insulin signalling increased
Reduces CHO absorption
Increased fatty acid oxidation
34
What effect does metformin have on:
a) HbA1c
b) Weight
c) micro/macro complications
d) Lipid profile
a) lowers HbA1c by lowering insulin resistance
b) reduces weight
c) prevents Micro/Macro complications
d) reduces TG and LDL
35
Why is metformin used in pregnancy?
Safe in gestational diabetes
36
What effect does metformin have on hyper/hypoglycaemia?
reduces hyerglycaemia
| NO hypos
37
What are the adverse effects of metformin?
```
GI symptoms: nausea, vomiting, abdo pain, diarrhoea, taste disturbance.
Lactic acidosis
Liver failure
Rash
Anaemia (rare)
```
38
How do you try and prevent GI effects with metformin?
Start low, go slow
39
What are the risk factors for lactic acidosis when using metformin?
high pre-existing risk
| MI, HF etc
40
Why do you have to measure eGFR with metformin?
Risk of renal toxicity
41
What changes in metformin dose have to be made with a) eGFR 30-45
b) eGFR < 30?
a) half dose
| b) stop meds
42
What is the second line treatment in T2DM?
Sulphonylureas
43
What kind of drugs are SUs?
Insulin secretagogues
44
Give an example of 1st generation SUs
Tolbutamide
45
Give examples of 2nd generation SUs
Glicazide
| Glibemclamide (aka Glyburide)
46
Why are 2nd generation SUs used more frequently?
more potent
47
When are sulphonylureas used?
intolerant to metformin
| add on to metformin
48
What is the action of SUs?
Bind to SUR1 sub unit
close kATP channel
beta cell depolarisation
insulin released
49
Why is it important that SUs act independently of plasma glucose?
can cause insulin to be released even with normal-low glucose levels
causes hypo
50
What effect do sulphonylureas have on:
a) HbA1c
b) micro/macro complications
c) weight
a) reduces HbA1c by inc insulin secretion
b) reduces MICRO complications only
c) weight gain
51
What are the adverse effects of SUs?
```
Can cause hypos
Weight gain
Does not prevent MACRO complications
Hypersensitivity (rare)
Blood dyscrasias (rare)
Liver dysfunction (rare)
```
52
When would SUs be 1st line?
Underweight T2DM patients
53
What groups of patients should care be taken with SUs?
Elderly
HGV drivers
(risk hypos)
54
What is the aim of Thiazolodinediones in T2DM?
Increase action of insulin at target sites
55
What is the action of mechanism in TZDs?
PPARy agonist
Allows transcription of GLUT4, lipoprotein lipase and fatty acid transport protein
Increased fatty acid storage
Reduced hepatic gluconeogenesis
56
How does PPARy act?
binds with RXR
| PPARy-RXR = transcription factor
57
How do TZDs effect:
a) HbA1c
b) Hyper/hypoglycaemia
a) reduces HbA1c by inc insulin sensitivity
| b) Reduces hyper/ no hypos
58
What are the adverse effects of TZDs?
Weight gain
Fluid retention
Does not prevent micro/macro complications
Increased bone fractures
59
Why do you get weight gain with TZDs?
Subcutaneous fat and fluid retention
60
Why do you get fluid retention with TZDs?
Na+ reabsorption in the kidney
61
What patients should you be aware of when perscribing TZDs?
HF patients
| Fluid retention could worsen HF
62
What contraindications are there for TZDs?
patients over 65
63
Give examples of TZDs
Pioglitazone
Rosiglitazone
Troglitazone
64
Why is pioglitazone the only licensed TZD?
Rosiglitazone causes MI
| Troglitazone causes liver failure
65
What are incretins derived from?
intestinal secretion of insulin
66
What is GLP-1 and where is it secreted?
Glucagon like peptide
| secreted from L cells in ileum and colon
67
What is GIP and where is it secreted from?
Glucose dependent Insulinotropic peptide
| K cells in jejunum/duodenum
68
What action do GIP and GLP-1 carry out on pancreas and what is the effect?
increase insulin production
increase glucose uptake in skeletal muscle
Decrease blood glucose
69
What action do GLP-1 have on alpha cells?
Decreases glucagon release
reduces glucose release
decreased blood glucose
70
What enzyme terminates action of GLP-1 dnd GIP?
Dipeptidyl peptidase 4 (DPP4)
71
What are incretin analogues?
GLP-1 agonists
72
What are the effects of incretin analogues?
```
Promote insulin secretion
Reduces HbA1c
Suppresses glucagon
Increases weight loss
Reduces appetite
```
73
What are the adverse effects of incretin analogues?
nausea (resolves in 6-8weeks)
injections
pancreatitis?
74
What are examples of incretin analogues? What are their modes of administration? what are their half lives?
Exenatide-BD-subcut injection-60-90mins
Exendin LAR-once weekly
Liraglutide-OD-subcut injection-10-14hrs (DPP4 resistant)
Lixisenatide-OD- subcut injection
75
What is the action of DPP4 inhibitors?
inhibit action of DPP4
| prolongs action of GLP1 and GIP
76
What are examples of DPP4 inhibitors?
Sitagliptin
| Vildagliptin
77
What are the effects of DPP4 inhibitors?
Weight neutral
No hypos
Suppress glucagon
Promotes insulin secretion (reduces HbA1c)
78
What are the adverse effects of DPP4 inhibitors?
Not very potent
No weight loss
Pancreatits?
79
What is the action of SGLT2 inhibitors?
prevent glucose re-absorption in proximal tubule
Glucosuria
Reduce blood glucose
reduces calories
80
What are the effects of SGLT2 inhibitors?
Reduce HbA1c
| Weight loss
81
What are the adverse effects of SGLT2 inhibitors?
Thrush
UTIs
(sugary urine=breeding ground for bacteria)
