Hypoglycaemia

Definition
  • Characterised by Whipple’s Triad:
    1. Low fasting plasma glucose (<3mM)
    2. Symptoms consistent with hypoglycaemia (see ‘Clinical Features’ below)
    3. Glucose administration immediately relieves symptoms
Aetiology/Causes
  • Most commonly iatrogenic due to excess insulin intake and sulphonylureas
    • However, it can also occur with normal/low insulin in causes that result in abnormal metabolism
  • There are both diabetic and non-diabetic causes (the EX-PLAIN mnemonic covers these)
  1. Diabetic causes:
    1. EXogenous Drugs (iatrogenic) which are mismatchedwith sugar intake are the most common
      • This is the most common cause
      1. Excess Insulin
      2. Sulphonylureas
      3. Other drugs can cause diabetic onset – e.g. post-transplant drugs, alcohol
    2. EXercise (without sufficient carbson board)
    3. Hot weather- insulin is more quickly absorbed
  1. Non-diabetic causes – typically cause hypoglycaemia through lack of antagonistic hormones- cortisol, catecholamines, thyroid hormone
    • Pituitary insufficiency causing a lack of cortisol/T3
      • Addisons is the main problem (there is insufficient cortisol which normally antagonises insulin)
    • Liver and renal failure
    • Alcohol
      • Alcohol is a key cause as it inhibits gluconeogenesis.
      • (It can also cause hyperglycaemia as it contains a lot of calories)
    • Insulinomas – tumours of islet B cells that present with hypoglycaemia
    • Immune disorders – antibodies to insulin receptor on tissues
      • E.g. Hodgkin’s
    • Non-pancreatic neoplasms

Clinical features
  1. Sympathetic overactivity occurs initially (at 2.5-3mM)- (PATHS)
    1. Pallor
    2. Anxiety
    3. Tachycardia
    4. Hunger
    5. Sweating
    6. Malaise and nausea also develops, later than the above symptoms
  1. Neuroglycopenia features(<2.5mM) typically develop later – these are similar to drunk patients. Confusingly, similar symptoms also occur with hyperglycaemia. The key symptoms are bolded here.
    • Drowsiness 
    • Confusion and loss of concentration
    • Incoordination and paraesthesia
    • Headaches
    • Personality changes
    • Later symptoms
      • Focal neurology
      • Collapse
      • Convulsions – hypoglycaemia is a key cause of seizures
      • Coma (<2.2mM)
Diabetic unawareness

Diabetic unawareness is a phenomenon where patients are unable to predict hypoglycaemia occurring as symptoms develop late

  • Occurs due to a lack of autonomic response
  • Presentation:
    • Do not have the early symptoms of sympathetic overactivity, weakness, malaise, nausea, and confusion
    • These patients therefore typically present with unheralded collapse or convulsions
  • Risk factors for diabetic unawareness:
    • Longstanding diabetes
    • Tight metabolic control (i.e. their baseline BGL is already low)
    • Elderly
    • Children
    • Alcoholics
    • Stress and depression
    • Nocturnalepisodes
  • Management of unawareness:
    • Improve hypo awareness
      • Education regarding warning symptoms and what to do when they develop
      • Increase capillary BGL measurement frequency
    • Relaxed glycaemic threshold – decreases the chance of hypo with the trade-off that a higher BGL is acceptable for the patient.

Diagnosis
  • Bedside
    • Obs
    • Capillary glucose – <3mM by definition
  • Blood tests are needed to determine the cause:
    • Blood Glucose Level (BGL)- will be low by definition
    • Insulin levels – refer back to EX-PLAIN for how this can exclude causes
      • High insulin is mainly due to exogenous drugs (insulin, sulphonylureas) or insulinomas
        • Distinguish with C-peptide – excludes endogenous insulin production (insulinomas)
      • Low insulin = look for other endogenous causes not related to insulin (assessing ketones can help further)
    • Ketones ketones increase when catabolic hormones are lost (and cause hypoglycaemia)
      • Low insulin/no ketones= paraneoplastic and immune causes
      • Low insulin/high ketones= pituitary insufficiency, Addison’s, or alcohol
        • Occurs as the anabolic effects of these hormones are lost resulting in ketosis

Management
  • There are 3 stages to the management of hypoglycaemia
    1. Resuscitation – i.e. treating the complications of hypoglycaemia including seizures and coma
    2. Glucose resuscitation (i.e. reversing hypoglycaemia)
    3. Secondary prevention of future episodes

Resuscitation

  • ABCDE approach is required in severe hypoglycaemia

Glucose resuscitation

  1. Administer 20mg of glucose – the method used depends on the patient’s consciousness
    • Delivery depends on whether patient is conscious or not (which indicates severity)
    • Alert patients – give PO 20mg glucose STAT
      • Can be in the form of buccal gel, juice, or tablet. Gel is preferred with impaired swallow
      • Reassess at 15 mins.
        • If this fails 3 times, give IV glucose or Glucagon
    • Unconscious patients
      1. IV Glucose (20mg) – 2 main options
        1. 10% 200ml glucose
        2. 20% 100ml glucose ran over 15 mins – less preferred because of a higher risk of thrombophlebitis but may be needed if the patient is volume overloaded (e.g. CCF)
  2. Glucagon 1mg IM can be given in severe hypoglycaemia instead of glucose (i.e. unconscious)
    • Antagonises insulin to reduce glucose uptake and increases glycogenolysis,  thus increasing BGL
    • NB two things:
      • Can only be used once
      • Glucagon is ineffective in 2 main situations:
        • Sulphonylurea-induced hypoglycaemia
        • Alcoholic hypoglycaemia
  • Monitor capillary BGL every 15 mins
    • Repeatedly administer glucose 20mg again every 15 mins until >4mmol
      • NB Glucagon can only be given once
  • Once BGL >4mmol/l , slow down delivery of glucose
    1. If patient has an intact swallow => Give starchy food
    2. Impaired swallow => Put patient on a slow glucose infusion
      • Give 510ml/hour of glucose
  • Aim for glucose at >6mmol/l before stopping a glucose infusion
    • This must be confirmed by 3 consecutive hourly reading

Secondary prevention

  1. Treat cause 
    • Reduce medication doses
    • Increase carb intake before exercise etc
    • Excise insulinoma
    • Manage Addison’s/hypothyroidism
  2. Manage diabetic unawareness
    • E.g. by using looser bgl controls or trying to stop alcohol abuse
  3. Review previous BGL readings 
  4. Driving advice is crucial in the UK
    • Ensure patient is recording their BGL before driving to ensure it is >5mmol
      • Take quick-acting snacks
    • If patient has 1 hypose s/he cannot drive for a year (DVLA must be notified)