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Flashcards in Type 2 Diabetes Deck (81):
1

What age range do T2DM patients present?

Middle age +

2

What is the BMI range in T2DM patients?

Normal-high (25+)

3

What history of autoimmune disease do T2DM patients have?

No history usually

4

Is there family history link with T2DM?

Yes, often have FHx

5

What will ketones appear as on T2DM urinalysis?

0 to +

6

Is HbA1c helpful at presentation?

No

7

What are the glucose levels at presentation?

10-25

8

How does T2DM present acutely?

Hyperglycaemic Hyperosmolar Syndrome

9

What are the C-peptide levels at presentation?

normal-raised

10

Are C-peptides present at 5 years post diagnosis?

Yes

11

Do T2DM patients present with complications? If so, how many?

Yes, 30%

12

What is the definition of T2DM?

Insulin resistance with relative insulin deficiency

13

How can obesity cause insulin resistance?

Obesity + lack of activity
Adiposity (inc FFAs, inc Adipokines)
Insulin resistance

14

How can obesity lead to relative insulin deficiency?

Obesisty + lack of activity
Adiposity (inc FFAs, inc Adipokines)
Lipotoxicity
Vulnerable beta cells (genetics) can't respond and produce more insulin

15

How do normal beta cells respond to obesity?

Compensatory increase in insulin production
Euglycaemia

16

Why is T2DM a progressive disease?

Beta cells deteriorate
No change in insulin sensitivity

17

What symptoms do T2DM patients present with?

Polyuria
Polydipsia
Blurred vision
Tiredness
Recurrent UTIs

18

What is the typical underlying cause of HHS?

undiagnosed T2DM
T2DM treated with diet only

19

What can trigger HHS?

CVS event (MI/Stroke)
Steroid therapy
Sepsis
Diuretics
High refined sugar intake

20

What is the aetiology in HHS?

Older patient
T2DM
If young then non white

21

What can precipitate HHS and why?

Frequent infection
Stress hormone release
(eg glucagon -> inc blood sugar)

22

What is the median glucose in HHS?

60

23

What will renal function be in HHS?

significant impairment

24

How is Na+ affected in HHS?

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)