Diabetes Flashcards
What are examples of microvascular complications of diabetes in the long term?
- neuropathy
- retinopathy
- nephropathy
What is the aetiology of microvascular complications of diabetes?
glycosylation of basement membrane proteins leads to leaky capillaries
What are examples of macrovascular complications of diabetes?
- IHD
- CVA
- Peripheral gangrene
What is the aetiology of macrovascular complications of diabetes?
dyslipidaemia, hypertension, hypercholesterolaemia
What is the onset of type 2 diabetes?
insidious
What is the onset of Type 1 diabetes?
always present acutely with ketosis
What are the symptoms of diabetes?
- tiredness, lethargy
2. polyuria, polydipsia
How does the symptoms of diabetes lead to worsening conditions?
- often drink lucozade or coke because of thirst
- glucose slowly rises further
- with other co-morbidities it become difficult to drink enough
- osmotic diuresis causes loss of water and a rise in sodium
- Eventually the glucose is VERY high, as is the sodium
How do you calculate osmolality?
cations + anions + glucose + urea
What can you simplify the equation for osmolality to?
2(cations) + glucose + urea
What cations are mostly used?
Na + K
What anions are mostly used?
Cl + bicarb
Do most people with T2 diabetes not know they have it?
yes
Why is it hard to spot T2 diabetes?
- have hyperglycaemia but no acidosis
- intermittent polyuria and polydipsia
- assumed prostate trouble or UTI
Why do T2 diabetes patients first present with complication?
- slow damage to endothelium
- micro and macrovascular damage
- of patients ignore polyuria first time present may be with complication
What does background diabetic retinopathy lead to?
- hard exudate
- blot haemorrhages
- microaneurysms
How do you treat background diabetic retinopathy?
imporve blood glucose control
Why are cotton wool spots (pre-proliferative) bad?
cotton wool spots represent ischaemia and new vessels not good and ischaemia causes new vessels to grow
How do you treat cotton wool spots?
pan-retinal photocoagulation
How does pan-retinal photocoagulation work?
- laser burns
2. kill of 1/3 of retina need less blood so no longer ischaemic so cotton wool spots will not drive new vessel growt
What is the general management of diabetic retinopathy?
- improve control of glucose
2. warn patient that warning signs present
How long does it take to benefit from good control of diabetes?
- 15years (a while) in newly diagnosed T2 diabetes
- Remained better mortality LT - legacy effect
- UKPDS
- Good control now prevents heart disease in the future
What was the DCCT study?
type 1 diabetes, good control improves outcome
What was the UKPDS study?
- new T2 put onto good control
2. low mortality in both groups for 15 years, but then good control improved outcome, LEGACY EFFECT
What did the ACCORD study show?
take older ppl who had poor control for long time and suddenly massively tighten control, already had CAD so increased unexpected death as have more hypos and tachycardias
What are the general drugs to manage hyperglycaemia?
- Diet and exercise
- Biguanide (metformin)
- Sulphonylureas (e.g. gluclazide)
- Insulin sensititsers: thiozolidinediones such as rosigilitazone (banned) or pioglitazone
- Insulin itself - gain weight
- Incretins (GLP-1 analogues)
- Gliptins (Dipeptidyl peptidase 4 inhibitors)
How is insulin used in T2DM?
- long acting (depot) insulin, such as insulin Zinc suspension
- with short acting insulin such as normal soluble insulin with each meal
- “insulatard” and “actrapid”
What are c peptide levels like in T2 and T1
T2 high and T1 low
Why is natural insulin not that great?
- when soluble natural insulin given sc form a hexamer under skin, which delays release
- inject 30 mins before meals
What are examples of insulin analgoues?
- Lispro switch B28 to B29 (pro to Lys)
2. Apart (pro 28) to Asp29
What are adv and disadv of insulin analogues?
- analogue rapid acting so can inject and eat
2. twice the cost of soluble insulin
Why do you want to make long acting insulin analgoues?
different alterations in the molecule to try and attain a plateau like concentration over time
What is insulin glargine?
long acting insulin seems to give least variation in plasma insulin levels for 24h after injection
Why are long acting insulin analogues good?
- once daily insulin injection improves quality of life as lower risk of hypoglycaemia
- gives background concentration of insulin to suppress ketogenesis
- normal pancreas makes continuous secretion of insulin
What is insulin detemir?
- 14 carbon fatty acid chain attached to B29
- Delayed onset 7h
- Can be used as part of basal bolus
What are advantages of insulin?
- Can give best control of HbA1c when combined with diet an exercise
- No side effects unlike metformin (diarrhoea), SU (occasional reactions), thiazolidinediones (rare hepatic and oesteoperosis)
What are the disadvantages of insulin?
- If you drive HGV, cannot work
- Exenatide exempt
- Hypoglycaemia common with good control
- Weight gain
- Increased insulin as a consequence
- Huge doses required in patients with T2 diabetes
Why is there weight gain with insulin?
- If glucosuria stops, many calories saved
- Increased appetite
- Improved well being
- Set point of body weight (hypothalamic)
- Poor control enables one to lose weight
Where is GLP-1 secreted from?
gut
What does GLP-1 do?
- signals pancreas to make more insulin
- increased hypothalamic satiety
- reduces gastric emptying
Can GLP-1 make you loose weight?
yes
What are examples of incretins?
- GLP-1: endogenous
2. Exenatide: synthetic version of exendin 4
What do DPP-4 inhibitors do?
inhibits DPP-4 enzyme which rapidly degrades incretins so own GLP-1 lasts longer
Do DPP4 inhibitors cause weight gain or weight loss?
weight neutral
What are examples of incretins (GLP-1 analogues)?
- Exenatide: injection
- Liraglutife
- semaglutide
What are examples of gliptins (DDP4 inhibitors)?
- vildagliptin
2. stiagliptin
Can incretins and gliptins be used for T1?
no only T2 as T1 need insulin
How do SGLT2 inhibitors work?
increased glucose secretion
What is an example of an SGLT-2 inhibitor and what are the side effects?
thrush and hypoglycaemia (if take with insulin or SU) common side effect, constipation, thirst
How do SGLT-2 inhibitors help with HbA1c and EGFR?
- Down for HbA1c, weight, waist circumference, BP
- EMPA-REG outcome
- Helps with heart failure
- EGFR immediately decrease but stays on prevents fall again
Where do SGLT-1 inhibitors act?
proximal tubule
What is the preferred initial pharmacogenic agent for T2DM?
metformin
What do you do if non-insulin monotherapy at max tolerated dose does not achieve or maintain A1C target after 3 months?
add 2nd oral agent, as GLP-1 receptor agonist or basal insulin
What should you consider for patients with long-standing suboptimally controlled T2DM and established atherosclerotic cardiovascular disease?
empagliflozin or liraglutide
GLP-1, DPP4 and SGLT2 favoured
Which one better?
- if don’t mind injections GLP-1
- compare these 3
- SGLT-2 and GLP-1 have heart benefit