E4 - Diabetes 2 Flashcards
(65 cards)
1
Q
What is the strategy/NICE guideline for treatment of T2DM?
A
1.) Diet/lifestyle interventions; trialled for 3 months. (w/regular GP meetings/testing)
2.) Monotherapy; anti-diabetic or hypoglycaemic agent.
> First-line: Metformin
> Second-line: SU (sulphonylureas), DDP-4i (DPP-4 inhibitors), pioglitazone.
3.) Dual therapy (after dose titrations tried); metformin + SU/DPP-4i/pioglitazone
4.) Triple therapy OR straight to insulin.
5.) Intensify insulin regime OR add drugs.
2
Q
What cautions are there for the first-line antidiabetic, Metformin?
A
Caution in renal impairment; may require dose adjustments, but cut off of renal impairment where Metformin not suitable.
3
Q
What is meant by the first/second intensification in relation to T2DM treatment?
A
First intensification: Dual therapy
Second intensification: Triple therapy
4
Q
What drug class is metformin and its therapeutic effect/consequences?
A
- Biguanide
- Increases glucose utilisation
- Decreases gluconeogenesis
(improves action of insulin)
5
Q
What is known about metformin’s mechanism of action/targets?
A
Not clear; thought to activate AMP kinase.
6
Q
What do sulphonylureas/prandial glucose regulators do and what is required?
A
- Stimulates insulin secretion
- Requires some functional β-cells; good for early stage T2DM.
7
Q
What is the mechanism of action for sulphonylureas/prandial glucose regulators?
A
Blockade of islet β-cell ATP-sensitive K+ channel; respectively bind at different sites within channel.
8
Q
What are prandial glucose regulators also known as? Give two examples.
A
Meglitinides:
- Repaglinide
- Nateglinide
9
Q
Name 3 sulphonylureas.
A
- Glicazide
- Tolbutamide
- Glibenclamide
10
Q
How does glucose-induced insulin release share similarities with the action of SUs/PGRs?
A
- Mimics increase of ATP:ADP ratio which results in K+ channel closing
- Blocking channel decreases K+ efflux, leads to accumulation of positive charge, membrane depolarisation, opening of VGCCs, exocytosis of insulin.
11
Q
What class of drugs does pioglitazone belong to and how does it work?
A
- Thiazolidinedione
- PPARγ-agonists ‘insulin sensitisers’
> Improved insulin action of insulin resistant cells etc
12
Q
What drug class does rosiglitazone belong to and why is it not used any more?
A
- Thiazolinediones
- License withdrawn as of 21/10/2010
13
Q
Name an α-glucosidase inhibitor and describe its mechanism of action.
A
- Acarbose
- Delays digestion & absorption of starch and sucrose; limiting breakdown hence limits absorption of glucose in the gut, dampening down peaks of glucose from a meal
- By inhibiting intestinal alpha glucosidases
14
Q
What is the issue with acarbose?
A
- Many GI side effects
- Reserved for later therapy
15
Q
What drug class do exenatide & liraglutide belong to?
A
GLP-1 mimetics/incretin mimetics
16
Q
What do DDP-4 inhibitors do and what are they also known as?
A
- Inhibits DPP-4; enzyme which normally degrades GLP1/incretin
- ‘Incretin enhancers’
- ‘Gliptins’
17
Q
What is the principle of incretin-based therapy?
A
- To push insulin-response curve back to the left
- To have the normal potentiating effect of incretins on insulin secretion
18
Q
Name 3 DPP-4 inhibitors.
A
- Sitagliptin
- Vildagliptin
- Saxagliptin
19
Q
What are the therapeutic effects of GLP-1 mimetics/DPP-4 inhibitors?
A
- Promote insulin secretion
- Reduce glucagon secretion (thus no increase in blood glucose)
- Reduce gastric emptying; allows much slower increase in blood glucose with meal absorption
- Promotes satiety (feeling of fullness; stop eating earlier)
- Reduces gluconeogenesis (hepatic glucose production, potentially inhibiting glycogen breakdown)
20
Q
What are the disadvantages with GLP-1 mimetics?
A
Administration via subcutaneous injection instead of PO.
21
Q
What is Bydureon and why is it preferable?
A
- Exenatide, a GLP-1 mimetic
- Weekly modified-release formulation (but still S.C. administration)
22
Q
What drug class do dapagliflozin, canagliflozin and empagliflozin belong to?
A
Sodium-glucose co-transporter 2 (SGLT-2) inhibitors
23
Q
What is the mechanism of action of sodium-glucose co-transporter 2 (SGLT-2) inhibitors?
A
- Inhibits renal glucose reabsorption
- Glucose normally filtered out of blood in the ultrafiltrate and then reabsorbed at PCT; mainly due to SGLT-2
- Reversibly inhibiting SGLT-2 in PCT reduces glucose reabsorption
- Glucose excreted in the urine (glycosuria); decrease in blood glucose
24
Q
What are the side effects with SGLT-2s?
A
Resulting glycosuria leads to:
- Polyuria
- Osmotic diuresis (glucose in urine increasing osmotic pressure and taking water with it)
- Polydipsia
- UTIs (prime environment for fungus/bacterial infections)
25
When is exogenous insulin required and what other drug therapies wouldn't be suitable at this point?
In advanced T2DM where:
- β-cell failure
- SUs ineffective as no insulin produced
- Combine insulin with other antidiabetic drugs
26
What are the acute complications associated with T2DM?
Extremes of glucose levels:
- Hypoglycaemia
- Hyperglycaemia; HHS
27
What is hypoglycaemia and how can it develop in T2DM?
- Low blood glucose;
28
What is hyperosmolar hyperglycaemic state (HHS) in T2DM? How does it present?
- Severe hyperglycaemia; > 40 mmol/L
- Hyperosmolar: glucose increases osmotic pressure in blood
- Without ketosis (unlike in DKA in T1DM; T2DM retains some β-cell function)
29
How is HHS treated?
- Managed as DKA
- Insulin given for hyperglycaemia (but much less insulin required than DKA; still have residual insulin production)
- Fluid/electrolyte correction for dehydration
30
Why are the long-term complications of T2DM noteworthy?
- Don't need to know
- Indicator of poor glycaemic control
- Major cause of morbidity and mortality
- Substantially impairs quality of life
- Cause of frequent hospitalisations
- Reduces life expectancy by 20 years in T1DM, 10 years in T2DM
- 80% of DM patients die from CV disease
- RIsk of stroke/heart attack increased by 2-3 fold
- Leading cause of blindness
- 1000 DM patients start dialysis every year in UK
- NHS spends 14 billion GBP PA on DM and its effects (10% of budget)
31
What is the difference between microvascular and macrovascular?
Microvacular; affect the small blood vessels (capiliaries)
Macrovascular; affect the larger blood vessels (medium-large arteries)
32
What are the 3 main microvascular complications of DM?
| Hint: well vascularised by capillaries/specific to DM
- Retinopathy (eye disease); high capillary network in the retina/back of the eye
- Nephropathy (kidney disease)
- Neuropathy (nerve damage); blood supply to nerves
33
What are the 3 main macrovascular complications of DM and why do they occur??
- Cardiovascular disease
- Cerebral vascular disease (stroke); large blood vessels affected in the brain
- Peripheral vascular disease
Accelerated atherosclerosis with DM; lipid deposits cause hardening.
34
What factors influence the development of secondary complications in DM?
- Duration of DM; longer you have the disease, the more likely the complications
- Glycaemic control
- Risk factors; smoking (increased CVD risk), genetics
35
What is the mechanism of microvascular complications (retino/nephro/neuropathy) in DM?
- Metabolites from elevated blood glucose e.g. sorbitol affecting protein function
- Glycation of proteins; attachment of glucose to protein can affect function
36
How prevalent in retinopathy in DM?
- Most common cause of blindness in
37
How can retinopathy be classified?
- Background (simple)
- Pre-proliferative
- Proliferative
- Maculopathy (when macula affected)
38
What does background (simple) retinopathy entail?
- Microaneurysm; tiny bulges in capillary network at the back of the eye (can rupture)
- Haemorrhages (bleeds)
- Exudates; leakages of lipoproteins from capillaries, harden to form deposits resulting in blurred/deteriorating vision
39
What does preproliferative retinopathy entail and how does it transition from background?
- Capillary network starts to fail
- Ischaemia of the retina; build-up of toxic metabolites = blurry vision
- Growth factors released to try and counter above and build new capillaries
40
What does proliferative retinopathy entail?
New capillaries formed from growth factors released during preproliferative stage; new blood vessels are prone to rupture (haemorrage); blindness v. likely.
41
Describe a patient's vision through the different stages of retinopathy.
- Background; normal
- Pre-proliferative; blurring of vision
- Proliferative; 'floaters', clouding, loss of vision
- Maculopathy; blurring/distortion of vision
- Advanced retinopathy; scarring can peel retina off the back of the eye; severe loss of vision
42
How can retinopathy be classified?
- Background (simple)
- Pre-proliferative
- Proliferative
- Maculopathy (when macula affected)
43
What defines each stage of diabetic nephropathy?
What is the timeline with regards to diagnosis of DM?
Early; microalbuminuria (albumin not being kept in blood)
Later; proteinuria, increased BP, decreased eGFR
Advanced; end-stage renal disease
Early; 5 - 10yrs (20 - 30%)
Later; 10 yrs
Advanced; 10 yrs
44
What does preproliferative retinopathy entail and how does it transition from background?
- Capillary network starts to fail
- Ischaemia of the retina; build-up of toxic metabolites = blurry vision
- Growth factors released to try and counter above and build new capillaries
45
What does proliferative retinopathy entail?
New capillaries formed from growth factors released during preproliferative stage; new blood vessels are prone to rupture (haemorrage) bleeding into the vitreous humor (viscous liquid that fills eyeball); blindness v. likely
46
Describe a patient's vision through the different stages of retinopathy.
- Background; normal
- Pre-proliferative; blurring of vision
- Proliferative; 'floaters', clouding, loss of vision
- Maculopathy; blurring/distortion of vision
- Advanced retinopathy; scarring can peel retina off the back of the eye; severe loss of vision
47
How are ACEis used in DM?
- Help limit diabetic nephropathy (renoprotective) even if BP is normal
48
What defines each stage of diabetic nephropathy?
What is the timeline with regards to diagnosis of DM?
Early; microalbuminuria (albumin not being kept in blood)
Later; proteinuria, increased BP, decreased eGFR
Advanced; end-stage renal disease
Early; 5 - 10yrs (20 - 30%)
Later; 10 yrs
Advanced; 10 yrs
49
What nerves can neuropathy affect?
- Cranial NS
- Autonomic NS
- Peripheral NS
50
What effects may arise from neuropathy?
- Erectile dysfunction
- Sweating
- Postural hypertension
- Bladder dysfunction
- Constipation
- Diarrhoea
51
Where does neuropathy most commonly effect?
Feet; increased risk of foot ulcers.
52
What are the symptoms of diabetic neuropathy?
- Loss of sensation
- Tingling
- Shooting pains
- Cramps
- Causalgia (burning sensation on touch w/o actual heat stimuli)
53
What is the aetiology (causation) of macrovascular complications in T1DM?
Glycaemic control
54
What is the aetiology of macrovascular complications in T2DM?
- Glycaemic control
- Genetic predisposition
- Metabolic syndrome
55
What is metabolic syndrome?
Cluster of risk factors associated with DM and vascular disease; much more common in overweight/obese:
- Glucose intolerance/DM
- Dyslipidaemia (high LDL, low HDL, high triglycerides)
- Hypertension
- Abdominal obesity
- Coagulation abnormalities
56
What is ischaemic heart disease and how does it relate to DM?
- Blockage (partial/full) of coronary artery with fatty depostits supplying the heart
- Can lead to MIs; carries increased risk of complications (heart failure, arrhythmias)
- Develops prematurely in DM, leading cause of death in DM.
57
How can the risk of ischaemic heart diseaes be mitigated in DM patients?
Management of risk factors:
- hypercholesterolaemia
- hypertension
- smoking cessation
58
How does stroke relate to DM?
- 10-fold increase in younger patients
- More likely to be fatal
- Less likely for TIAs; warnings of major stroke
- Hypertension control important
59
What characterises peripheral vascular disease?
- Intermittent claudication (cramping; ischaemia in muscles from blockage of larger vessels)
- Intermittent ulceration; poor blood supply = poor healing = poor supply of WBCs
- Hence risk of gangrene/amputation
- Risk of other vascular events; e.g. DVTs > pulmonary embolism
- Diabetic foot ulcers
60
What HCPs are involved in the hospital care DM team?
- Consultant/diabetologist
- Diabetes specialist nurse
- Ophthalmologist (eye doctor)
- Psychologist
- Medical specialists
61
What risk factors are important in preventing microvascular complications?
- Good glycaemic control
- Control of hypertension (ACEi - limit nephropathy even in normotensive (renoprotective), ATRA, CCB; different to A/C rule)
> Target: SYS
62
What risk factors are important in the management of macrovascular complications?
- Good glycaemic control
- Control of hypertension
- Control of dyslipidaemia (NICE guidelines = statins for all DM > 40 yrs)
- Use antiplatelet drugs (low dose aspirin, clopidogrel; lower CVD risk)
63
What does the annual assessment for DM complication risk involve?
- Blood tests; HbA1c, glucose, BP, lipids (higher risk of CVD in DM)
- Eye examination (retinopathy)
- Kidney function (nephropathy)
- Footcare (inc. podiatrist; foot consultant) DO NOT SELF-MEDICATE
- Review of care plan, other info, education, specialists
64
What HCPs are involved in the primary care DM team?
- GP & practice nurse
- Dietitian
- Optometrist
- Podiatrist/chiropodist
- Pharmacist
65
What HCPs are involved in the hospital care DM team?
- Consultant/diabetologist
- Diabetes specialist nurse
- Ophthalmologist (eye doctor)
- Psychologist
- Medical specialists
