W7 Pathophysiology of T2DM (SM) Flashcards
Pathophysiology of T2DM:
What is the definition of T2DM?
Type 2 diabetes mellitus is a metabolic disorder in which persistent hyperglycaemia is caused by a combination of deficient insulin secretion (β-cell dysfunction) and resistance to insulin action (impaired insulin-mediated glucose utilisation in the liver, adipose, muscle and others)
= Impaired Insulin secretion and Impaired Insulin action
What are the primary causes of T2DM?
- Non-modifiable: Genetic predisposition/family history
and ethnicity (Asian, African and Afro-Caribbean)
• Modifiable: Obesity, sedentary lifestyle and overnutrition
(high-calorie intake and less-calorie expenditure)
What are the secondary causes of T2DM?
• Drugs (long-term use of corticosteroids, thiazide diuretics,
β-blockers, statins)
• Hormones (high cortisol in Cushing’s, high growth
hormone in acromegaly)
• Pancreatic disease (chronic pancreatitis, surgery, cystic
fibrosis, tumour)
• Genetic conditions (Prader-Willi and others)
• Some secondary complications at the time of diagnosis, often overweight (but not always)
• Onset at any age (usually >40 years; >25 years in Asian and African ethnics)
• gradual onset
• Lead to long-term secondary complications
Acute complication of T2DM
Hyperosmolar hyperglycaemic state (HHS):
What is it?
What are the symptoms?
- Severe hyperglycaemia (often over 40 mmol/L).
• It can develop over weeks through a combination of illness (e.g.infection) and dehydration in people with type 2 diabetes (stopping diabetes medication during illness)
• HHS does not lead to diabetic ketoacidosis (presence of ketone bodies in urine) and hence previously known as hyperglycaemic hyperosmolar non-ketotic coma, HONK
Dehydration
(polyuria, polydipsia,
glucosuria)
low cerebral blood flow
Low renal flow
= Diabetic coma medical emergency
= manage glycemic control and restore fluid homeostasis
Peripheral circulatory failure
What are the Secondary (long-term) complications of DM?
Microvascular
• Visual Impairment (Retinopathy)
• Nerve Damage (Peripheral Neuropathy)
• Renal Disease (Nephropathy
Pathophysiology of Microvascular disease in DM:
Chronic hyperglycaemia (uncontrolled)
Endothelial damage, oxidative stress, inflammation
Altered blood flow, endothelial dysfunctions, extra vascular protein aggregation, coagulation, ischémie and organ dysfunction
= visual impairment (retinopathy)
= nerve damage (peripheral neuropathy)
= renal disease (nephropathy)
What are the 2 stages of diabetic retinopathy?
Most common cause of vision impairment in individuals with diabetes mellitus
2 stages: non-proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR).
What are the 2 stages of diabetic retinopathy?
Most common cause of vision impairment in individuals with diabetes mellitus
2 stages: non-proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR).
What is Diabetic Nephropathy?
- Occurs in 30–40% of patients within 25 years.
- The combination of hyperglycaemia and hypertension drives glomerular damage, including thickening of the basement membrane, atrophy, interstitial fibrosis and arteriosclerosis/glomerulosclerosis.
- These changes initially result in glomerular hyperfiltration and subsequently, progressive loss of renal function.
- Optic disc, where the optic nerve and blood
vessels exit the eye - Fovea, the region of sharpest vision
- Macula, the central area of the retina
- Retinal microvasculature damage causes basement membrane thickening,
increased capillary permeability, and microaneurysms formation. - These changes lead to intravascular coagulation, resulting in retinal ischaemia
(cotton wool spots), which drives the formation of new vessels within the retina
(neovascularisation). These new vessels are fragile and may rupture, causing
retinal bleeds (vitreous haemorrhage). - The lack of lymphatic drainage within the retina causes fluid accumulation in
the presence of hyperglycaemia resulting in macular oedema
What is Diabetic Nephropathy?
• Occurs in 30–40% of patients within 25 years.
• The combination of hyperglycaemia and hypertension drives glomerular damage, including thickening of the basement membrane, atrophy, interstitial fibrosis and arteriosclerosis/glomerulosclerosis.
• These changes initially result in glomerular hyperfiltration and subsequently, progressive loss of renal function.
What is Diabetic Neuropathy?
What are the 2 types?
- Progressive loss of nerve fibres (degeneration)
~25% of people with diabetes - Peripheral and Autonomic
What is Peripheral neuropathy? (sensory or motor neurones)
- Mainly in feet, progress to loss of sensation and increased risk of foot ulcers
- Symptoms include tingling and numbness, loss of ability to feel pain, loss of ability to feel changes in temperature, loss of coordination and burning or shooting pains.
What is Autonomic neuropathy?
- Gastroparesis –bloating, constipation or
diarrhoea. - Loss of bladder control, leading to incontinence
- Irregular heartbeats, problems with sweating
- Impotence
Macrovascular diseases
Peripheral Vascular Disease, Diabetic Foot Ulcer:
Due to persistent hyperglycaemia-induced micro and macrovascular damage, neuropathy, vascular insufficiency,
and secondary infection due to trauma of the foot
Neuropathic– Neuroischemic– Ischemic– Skin infection– Amputation
Diabetic foot ulcers are an injury to all layers of skin, necrosis or gangrene that usually occurs on the soles of the
feet of diabetic patients and are susceptible to bacterial invasion resulting in infection and decay.
Diabetic gangrene is a tissue death caused by a blockage of blood vessels (ischemic necrosis) due to microemboli atherothrombosis caused by occlusive peripheral vascular disease
What are the Secondary (long-term) complications of DM?
Microvascular and Macrovascular??
Microvascular:
* Visual Impairment (Retinopathy)
* Nerve Damage (Peripheral Neuropathy)
* Renal Disease (Nephropathy)
Macrovascular
o Cardiovascular disease
o Cerebral vascular disease (stroke)
o Peripheral vascular disease (diabetic foot)
