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Aims
> Summarise the complications of diabetes mellitus. > Describe pathophysiology of select complications. > Describe some treatments available.
Patient D
White, Elderly female Initial Diagnosis 1985 Type II Diabetes Poorly controlled:
PERIPHERAL VASCULAR DISEASE Peripheral neuropathy & vagal nerve damage Strokes & TIAs (Cerebellar focus Loss of Balance) Retinopathy & Cataracts Silent heart attacks
Treatments
Leg stenting Hypertensive drugs Retinal LASER surgery damage control Cataract surgery Endarterectomy Metformin;
Formerly Tolbutamide
Diabetic Retinopathy
Damage to the retina of the eye. On-going inflammation and vascular remodelling may occur over periods of time where the patient is not fully aware of the extent of the disease.
Almost invariably asymptomatic until patient has catastrophic intraocular sightthreatening haemorrhage.
Retinopathy is treatable.
IRMA
CARDIOVASCULAR COMPLICATIONS
> Coronary heart disease is recognized to be the cause of death for 80% of people with diabetes, however, the NHS states that heart attacks are largely preventable. > Both type 1 and type 2 diabetics are at greater risk of developing heart disease. > Serious cardiovascular disease may develop in diabetics before the age of 30 (does NOT only affect the middle-aged and elderly).
Symptoms include: Pain in the chest Shortness of breath Arrythmias Swelling of ankles
Ischaemic heart disease Stroke Peripheral Vascular Disease Hypertension Myocardial Infarctions
There are several ways in which cardiovascular complications can be increased by diabetes.
1)
2) Impaired Endothelial Function Effects: Reduced release of NO, therefore greater arterial contraction and reduced blood flow. Increased platelet aggregation due to lack of NO. May be caused by: Effects of increased VLDL s Osmotic effects of glucose Modification of LDL s
Macrophages in atherosclerotic plaque accumulate lipids as they can recognize modified lipoproteins: They have receptors for AGEPs called RAGE
Activation of macrophages (which take up LDLs) Release of chemokines and growth factors from macrophages
5) Hyperinsulinaemia In some Type 2 diabetics this may also have independent effects which enhance atherosclerosis.
People with diabetes and signs of coronary heart disease will be advised to make lifestyle changes such as stopping smoking, eating a healthy, balanced diet and incorporating physical activity into their lives. In general, severity can be controlled by tight control of blood glucose. Medication may also be prescribed. Common medications for treating heart disease include:
Neuropathy
Cause: - pressure; ischemia; metabolic abnormalities Types: -pressure palsy; mononeuropathies; diffuse sensory and autonomic polyneuropathy Mechanisms: - polyol pathway; protein glycation; altered intracellular redox potential
AGE in endothelial cells of endoneural micro vessels Decrease cytoskeletal activity, induced protein aggregation in cytoplasm, alter ligands for cell surface receptors AGE modified peripheral nerve myelin susceptible to phagocytosis leading to demyelination Glycation of extracellular matrix proteins impairs regeneration Oxidative stress compounds actions
Sorbitol and fructose accumulate in cells with increased glucose Sorbitol and fructose diffuse slowly Osmotic effects damage nerve cells
Effects
Distal symmetrical sensory and autonomic neuropathy Disabling pain from paraesthesia Focal neuropathies Autonomic neuropathy: Gustatory
Diarrhoea/gastroparesis Postural hypotension Respiratory arrest Cardiovascular (early vagal; later sympathetic denervation) sweating Urinary retention Impotence
Umbrella term for. Diabetic foot ulceration Diabetic foot infections Neuropathic osteoarthropathy of the foot
PVD + neuropathy + developing infections + decreased ability to clear infections = severe foot problems (e.g. infection, gangrene, amputation)
Aetiology
Foot ulcers due to ischemia &/or neuropathy Sensory deficits and application of abnormal forces Initiating injury (e.g. thermal trauma, ill fitting shoes) Weak skin Defective healing
Charcot foot
A neuro-arthropathic process withosteoporosis, fracture, acute inflammation and disorganisation of foot architecture Slight trauma fracture of a weakened bone increased on adjacent bones gross destruction persisting deformity increased risk of secondary ulceration.
Summary
Multiple complications arise from poorly controlled diabetes mellitus. Pre-dominantly PVD Micro/Macrovascular Disease Co-morbidities Controlled, reduced morbidity and mortality, but not to level of normal population (Type II) Prevention of complications lower blood glucose.
Any Questions?