Diabetes Flashcards
Microvascular complications of Diabetes
Retinopathy
Neuropathy
Nephropathy
Macrovascular complications of Diabetes
Ischaemic heart disease
Coronary heart disease
Peripheral vascular disease
Presentation of microvascular disease
5yrs after T1DM
May be presentation for T2DM
Diabetic eye disease
Diabetic retinopathy
Macular oedema
Cataract
Glaucoma
Diabetic retinopathy
Damage to retinal capillaries in retina due to high glucose levels in the blood
2nd commonest cause of blindness
When looking at the retina, hard exudate, blot haemorrhages and microaneurysms may develop
Pathological findings for diabetic retinopathy
Loss of pericytes therefore reduced regulation of blood flow to retina
Thickening of basement membrane
Ischaemia - VEGF production and increased capillary permeability to promote angiogenesis
Capillary closure
Clinical stages of retinopathy
Non-proliferative (mild, moderate, severe) - ischaemia
Proliferative - angiogenesis
Macular oedema
Treatment of retinopathy
Diabetic control and blood pressure control
Panretinal photocoagulation
Focal laser treatment
Intravitreal anti-VEGF antibodies
Panretinal photocoagulation
Laser treatment used to prevent new blood vessels from forming in ischaemic areas and causes old blood vessels to scar up –> reduces oxygen demand to reduce angiogenic factors
Prevents vitreous haemorrhage and neovascular glaucoma
Used to treat diabetic retinopathy
Side effect: peripheral visual field constraints
Focal laser treat
A laser is used to burn areas of retinal leakage to slow leakage and reduce the amount of fluid in the retina
Used to treat diabetic retinopathy
Intravitreal anti-VEGF antibodies
Antibodies target VEGF to reduce angiogenesis and improve diabetic retinopathy
Diabetic neuropathy
High blood glucose causes damage to the small blood vessels which supply the nerves therefore the nerve fibres are damaged or disappear
Only symptom relief available, and improve blood glucose control
Types of neuropathy
Mononeuropathy - affects a single nerve or group of nerves e.g. carpal tunnel syndrome
Peripheral neuropathy - damage to nerves of the extremities e.g. charcot foot, neuropathic ulcer and callus
Entrapment neuropathy/nerve compression syndrome
Peripheral neuropathy
Divided into:
Autonomic neuropathy - nerves to organs affected so can cause gastroparesis, postural hypotension, erectile dysfunction, etc.
Motor neuropathy
Sensory neuropathy
Charcot foot
Bones in foot are weakened and repeated use causes fractures but neuropathy causes loss of sensation (including touch and pain) and results in further damage causing distortion of the shape of the foot
Nephropathy
Common cause of end-stage renal failure requiring dialysis
High blood glucose causes damage to the glomerular basement membrane and results in leakage of proteins and glucose into the urine (albuminuria and glycosuria)
Pathological findings of the diabetic nephropathy
Basement membrane thickening - due to ROS and proteins accumulating
Loss of glomerular podocytes - loss of filtration barrier
Glomerular sclerosis - scarring of the glomerular capillaries
Mesangial expansion to clear the ROS and proteins accumulating on the basement membrane of the glomerulus
Management of diabetic nephropathy
Blood pressure control Blood glucose control RAS system blocker Reduce CVD risk Possible renal transplant
Preventing macrovascular complications
Address modifiable risk factors e.g. blood pressure, lipids/cholesterol, smoking, glucose control
Metabolic syndrome
Central/visceral obesity Insulin resistance (pathophysiological mechanism) BMI>30kg/m2 Dyslipidaemia Hyperglycaemia Hypertension
Complications associated with obesity
Increased blood volume, viscosity and vascular resistance
Hypertension, Left ventricular hypertrophy, Coronary artery disease, Stroke
Obstructive sleep apnoea, hypercapnia/hypoxia, pulmonary hypertension
Non-alcoholic fatty liver disease (steatohepatitis/NASH), cirrhosis, portal hypertension, hepatocellular cancer, gallstones, reflux
Breast, endometrial, oesophageal, colon, gallbladder, renal and thyroid cancer
PCOS, male hypogonadism, subfertility
Osteoarthritis, gout
Depression and eating disorders
Genes associated with T1DM
HLA DR3-DQ2 and HLA DR4-DQ8
Foetal programming
Epigenetic modification of gene expression in response to stimuli or insult during critical periods resulting in persistent biological effects
Slow-acting hormones regulating body weight
Insulin and Leptin
Rapid-acting hormones regulating meal size
Cholecystokinin - stop eating
Ghrelin - increase eating/hunger
PYY hormone - sateity
roux-en-Y gastric bypass
A small pouch is created at the top of the stomach with staples and this is attached to the intestines lower down to bypass the rest of the stomach
Limits the amount eaten by altering hormone levels produced by the gut
May lead to micronutrient deficiencies, irreversible
Laparascopic adjustable banding
A balloon and soft silicone ring with saline fluid are used to create a smaller top part of the stomach to limit the amount of food eaten
Reversible
Physiological changes seen in T2DM
Increased levels of leptin and leptin resistance resulting reduced satiety and increased feeding
Gut microbiota changes - possible reduction in bacterial variety
Type 1 Diabetes
Reduced secretion of insulin or absence of insulin secretion due to autoimmune destruction
Type 2 Diabetes
Insulin resistance with a lack of beta cell reserve
Pt may initially appear hyperinsulinaemic and euglycaemic as there is a rise in insulin production initially when resistance develops but, as resistance continues, the beta cells are unable to keep up resulting in hyperglycaemia
Absence of insulin
Body enters starvation state to cause: Gluconeogenesis Reduced glycogenesis Increased glycolysis Increased lipolysis Ketogenesis in liver
How to the typical symptoms of Diabetes present?
High levels of glucose exceeds renal threshold (10mM) so glycosuria occurs which draws water as well causing polyuria with large volumes of urine passing during the day and night
Polyuria leads to polydipsia
Diabetic ketoacidosis
Occurs in T1DM
Starvation state due to absence or low insulin causes ketogenesis which accumulate to cause ketoacidosis
A&E presentation of patient with T1DM
Confusion and apparent breathlessness due to ketoacidosis
Pt is breathing deeper and faster (tachypnoea) to reverse the metabolic acidosis
Treating DKA
Rehydrate to correct dehydration due to polyuria
Insulin to stop ketogenesis and cause GLUT4 translocation
Hyperosmolar Hyperglycaemic State
Severe hyperglycaemia occurring in T2DM
High glucose takes water with it causing more sodium retention (hypernatraemia) leading to high osmolality
Can cause confusion or coma
Normal fasting plasma glucose level
4.0 to 5.4 mmol/L
Diabetic plasma glucose
Fasting plasma glucose >7.0mmol/L
HbA1c > 6.5% or 48mmol/L
GTT > 11.1mmol/L
Impaired fasting glucose
Fasting plasma glucose between 6.0-7.0mmol/L
Hypoglycaemic stress
Glucose falls to between 2mM and 4mM
Patients develop symptoms of sympathetic overactivity e.g. increased heart rate, sweating
Neuroglycopenia
Blood glucose falls below 1.5mM so there is not enough glucose provision for the brain so the patient becomes unconscious
Treating hypoglycaemia
Intravenous insulin and subcutaneous glucagon
Glycation
Bonding of glucose to proteins or lipids e.g. glycated Hb (used to detect levels of glucose)
Glycation of endothelial proteins results in micro- and macrovascular complications
