Diabetes complications and medication

• Short term complications relate to immediate insulin and blood glucose management:

  • Hypoglycaemia
  • Hyperglycaemia and diabetic ketoacidosis
• Chronic high blood glucose levels cause damage to the endothelial cells of blood vessels

  Also causes immune system dysfunction
• Macrovascular complications:

  • Coronary artery disease
  • Peripheral ischaemia and diabetic foot ulcers
  • Stroke
  • Hypertension
• Microvascular complications:

  • Peripheral neuropathy
  • Retinopathy
  • Kidney disease
• Diabetic nephropathy is characterised by gradually increasing urinary albumin excretion and blood pressure as the glomerular filtration rate falls insidiously towards end-stage renal disease
• Investigations for kidney disease:

  • Early morning first void urine sample for albumin:creatinine ratio
  • Bloods for serum creatinine
• A diagnosis of diabetic kidney disease is made if there is a persistent reduction in kidney function (eGFR <60) or persistent proteinuria for 3 months or more
• ACE inhibitors are started in type 2 diabetics with chronic kidney disease

  SGLT-2 inhibitors can also be added
• Diabetics with chronic kidney disease need strict blood pressure control and should aim to keep their blood pressure below 130/80
• Diabetes and peripheral artery disease:

  • Atherosclerotic occlusive disease of lower extremities
  • Hyperglycaemia, dyslipidaemia and insulin resistance
  • Diabetes is associated with increased circulating levels of pro-inflammatory cytokines
• symptoms of PAD:

  • intermittent claudication
  • Skin pallor
  • Cyanosis
  • Reduced sensation
  • Dependent rubor - buerger's test
  • Muscle wasting
  • Hair loss
  • Poor wound healing - ulcers / gangrene
• Investigations for PAD:

  • Ankle-brachial pressure index <0.9 indicates PAD
  • <0.3 indicates severe disease to critical ischaemia
  • Duplex ultrasound
  • Angiography - contrast highlights the arterial circulation
• Management of PAD:

  • Life style changes - stop smoking
  • Optimise management of co-morbidities
  • Exercise training
  • Atorvastatin 80mg
  • Clopidogrel 75mg
  • Surgical options - angioplasty and stenting, bypass
• Acute limb ischaemia the 6 P’s:

  ·       Pain

  ·       Pallor

  ·       Pulseless

  ·       Paralysis

  ·       Paraesthesia

  ·       Perishing cold

  Needs urgent thrombolysis, thrombectomy or surgical intervention
• the prolonged hyperglycaemia in diabetics can lead to peripheral neuropathy

  Leads to a polyneuropathy with a glove and stocking distribution - almost always bilateral
• Patients with diabetic polyneuropathy experience numbness, burning, tingling and paraesthesia

  pain is usually worse at night

  Can be associated with motor neuropathy - weakness, wasting, cramps and twitching
• Pain relief for diabetic neuropathy:

  • Duloxetine
  • Gabapentin
  • Pregabalin
  • Amitriptyline
• Diabetes can cause autonomic neuropathy:

  • Postural hypotension
  • Gastroparesis
  • Excessive sweating
• Charcot neuroarthropathy is a complication of severe neuropathy

  Causes bony destruction of the foot and presents with acute swelling

  Immobilization in a non-weight bearing cast is the treatment of choice and should be continued until the swelling and temperature in the foot has resolved
• Diabetic retinopathy is the most common diabetic complication:

  • Non-proliferative retinopathy: early changes without vision loss
  • Proliferative retinopathy: sight threatening retinopathy
• Microaneurysms occur in the eyes of diabetics when there is damage to the capillaries

  Seen as small red dots in the back of the eye when the damaged vessels leak blood

  Damaged blood vessels leak fluid into the retina - macrophages enter- hard exudates seen

  Cotton wool spots are seen due to chronic ischaemia
• Chronic ischaemia of the eye in diabetics causes the release of vascular growth factors - causes new blood vessels to grow in the retina

  These new unsupported vessels give rise to haemorrhages - vitreous haemorrhage can cause sudden loss of vision
• Erectile dysfunction is common in diabetics

  Treatment is with phosphodiesterase type 5 inhibitors - enhance the effects of nitric oxide on smooth muscle and increase penile blood flow
• Metformin:

  • Increases insulin sensitivity and decreases glucose production by the liver
  • Does NOT cause hypoglycaemia
  • Does NOT cause weight gain
  • GI side effects - try modified release metformin
• SGLT-2 inhibitors:

  • dapagliflozin, empagliflozin
  • Block the action of SGLT-2 protein and cause more glucose to be excreted in the urine
  • Risk of hypoglycaemia if used with other antidiabetics
  • Reduce the risk of cardiovascular disease
  • Lowers blood pressure
  • Weight loss
  • Increased urine output and frequency - presence of glucose increases risk of genital and urinary infections
  • Increased risk of DKA
• Pioglitazone:

  • Increases insulin sensitivity and decreases liver production of glucose
  • does NOT cause hypoglycaemia
  • weight gain
• Sulfonylureas:

  • Gliclazide
  • Stimulate insulin release from the pancreas
  • High risk of hypoglycaemia - aim for HbA1c of 53
  • Weight gain
• GLP-1 is an incretin that is released from the GI tract and stimulates insulin secretion and slows absorption in the GI tract

  • Semaglutide
  • GLP-1 mimetics can be given in diabetics
  • Reduce appetite
  • Weight loss
  • Liraglutide can be used for weight loss in non-diabetic patients
  • Given by SC injection
• DPP-4 inhibitors:

  • Block the action of DPP-4 which allows increased incretin activity
  • Sitagliptin and alogliptin
  • Do NOT cause hypoglycaemia
  • Headaches
  • Low risk of acute pancreatitis
• Diabetic sick day rules:

  • ACE inhibitors - stop if risk of dehydration to reduce risk of AKI
  • Metformin - stop if risk of dehydration to reduce risk of AKI
  • GLP-1 mimics - stop if risk of dehydration to reduce risk of AKI
  • Sulfonylureas - high risk of hypoglycaemia if low oral intake
  • SGLT-2 inhibitors - stop if acutely unwell due to risk of DKA
• Antidiabetics can be started again once feeling better and eating/drinking for 24-48 hours
• Neuropathy:

  • Symmetrical polyneuropathy - loss of vibration, pain and temperature sensation
  • Mononeuropathy - damage to a single cranial or peripheral nerve e.g. third nerve palsy
  • Diabetic amyotrophy - affecting the lumbosacral plexus - symmetrical pain, weakness and wasting
  • Autonomic neuropathy