Lecture 10: Diabetes 2 Flashcards
What are the acute complications of DM?
Hypoglycaemia
DKA
HHS (hyperosmolar hyperglycaemic state)
What are the chronic complications of DM?
Microvascular (eyes, kidneys and nerves)
Macrovascular (stroke, heart disease and peripheral vascular disease which can lead to diabetic foot disease)
Under what circumstances can hypoglycaemia occur in DM?
Taking too much insulin
True or false: patients with DKA have increased fluid (overhydrated)
False: they become very dehydrated
What is the pathogenesis of DKA?
deficiency of insulin but increase in counter regulatory hormones so:
- breakdown of protein for gluconeogenesis
- breakdown glycogen to produce glucose
–> both of which contribute to the hyperglycaemia (result in polyuria and dehydration)
- breakdown of triglycerides (lipolysis) increases free fatty acids that are converted to ketones to produce energy via the Krebs cycle
- accumulation of ketones results in ketoacidosis
What causes the chronic macrovascular complications of DM?
hyperlipidaemia
Hypertension
endothelial dysfunction caused by high blood pressure and high cholesterol and diabetes resulting in artery clogging heart disease and strokes
What causes the chronic microvascular complications of DM?
glycation of proteins
polyol production in the form of sorbitol
Protein kinase C activation
What factors can influence the development of chronic complications in DM?
- genetic susceptibility
- glycaemic control
- duration of DM
- blood pressure
- cholesterol
- medical care received
How does hyperglycaemia affect microvascular function?
Hyperglycaemia results in the formation of advanced glycation end (AGE) products formation that cause altered function of proteins and increase in pro-inflammatory cytokines that change blood flow, coagulation, vascular cell growth and endothelial permeability
–> causes inflammation that can destroy nerves and small arteries
Why do 50% of newly presenting patients with T2DM already have one or more chronic complications at diagnosis?
on day of diagnosis, patients have lost 50% of beta cell mass so damage has been going on for a long time
What are the stages of diabetic nephropathy leading to renal failure?
normal renal function
–> microalbuminuria
–> overt proteinuria
–> glomerular destruction (increased serum creatinine, decreased eGFR)
–> renal failure
What occurs in diabetic retinopathy?
intraretinal haemorrhages (dot and blot haemorrhages)
- can result in formation of new blood vessels that encroach on the retina and block the retina (these blood vessels may be more susceptible to haemorrhage contributing to blindness)
What occurs in diabetic neuropahy?
- peripheral neuropathy (numbness and tingling in hands and feet - eventually all sensation can be lost)
- loss of sensation results in formation of pressure ulcers and poor arterial supply results in poor healing of ulcers
–> become easily infected and can lead to amputations
How is glycaemic control monitored?
- symptoms
- urinalysis (redundant)
- capillary glucose (finger prick)
- HbA1c
- Interstitial glucose (continuous glucose monitoring (CGM), flash glucose monitoring)
What is flash glucose monitoring?
small needle remains in arm attached to sensor and can be worn for up to 14 days
- data transmitted to monitor when swiped over the sensor (flash)
–> now acts more like a CGM following updates and alarms to warn of hypoglycaemia
What is the difference between continuous glucose monitors and flash glucose monitors?
Sensor monitors interstitial glucose and the data can be wirelessly transmitted to insulin pumps to adjust the levels of insulin being secreted by the pump (artificial pancreas maintains good glycaemic control)
–> CGMs are more expensive than flash glucose monitors
What is the downside of HbA1c testing for monitoring of glycaemic control?
It is an average over 3 months and doesn’t give the extremes (E.g. person may have good glycaemic control and have the same average as a person with hypoglycaemia half the time and hyperglycaemia the other half)
What is more helpful in assessing glycaemic control?
Time in range (gives time patient was out of the normoglycaemic range and time in range) - can only happen with the newer glucose monitors
How is T1DM treated?
Glycaemic control: insulin and diet
Treat to prevent complications: antihypertensive drugs, ACE inhibitors (to treat nephropathy), statins (for hyperlipidaemia)
What future T1DM treatments are being looked into?
prevention of T1DM by immunotherapy (vaccinations) to prevent autoimmune disease
What insulin is typically received by DM patients?
Genetically engineered insulin analogues
What are the aims of DM treatment?
- avoid/reduce symptoms of hyperglycaemia
- avoid/reduce hypoglycaemia (make sure treatment doesn’t cause hypoglycaemia)
- restore metabolism and glucose homeostasis to as near normal as possible
- delay or prevent development of chronic complications
True or false: when fasting/not eating, insulin levels in the serum is zero until a meal is consumed?
False: there is always low level baseline secretion of insulin (has other roles in the body)
- rise in insulin with consumption of food
How is insulin given to diabetic patients to mimic physiological insulin concentrations in non-diabetics?
Basal-bolus regime
- one long term basal insulin injection to mimic low level continual insulin concentration
- one injection of prandial rapid insulin with consumption of food (adjusted according to carbohydrate content of meals and blood glucose levels)
