DKA, HHS and Hypoglycaemia

Question 1

How is insulin produced?

Answer 1

• GLUT2 transporters mediate the entry of glucose into beta cells.
• Glucose is phosphorylated by the rate limiting enzyme glucokinase.
• This modified glucose becomes is further metabolised to create ATP.
• This increased ATP:ADP ratio causes the ATP-gated potassium channels in the cellular membrane to close, preventing K⁺ from being shunted across the cell membrane.
• The ensuing rise in positive charge inside the cell, due to the increased concentration of K⁺, leads to depolarisation of the cell.
• The net effect is activation of voltage-gated calcium channels, which transport Ca²⁺ into the cell.
• The brisk increase in intracellular Ca²⁺ concentrations triggers export of the insulin-storing granules by a process known as exocytosis.
• The ultimate result is the export of insulin from beta cells and its diffusion into nearby blood vessels.
• Insulin release is a biphasic process (stored released and then produced released)

Question 2

What is Whipple’s triad of hypoglycaemia?

Answer 2

• Symptoms of low blood glucose, autonomic and neuroglycopaenic
• Measured blood glucose <2.8mmol, <4mmol

Question 3

What are the features of the Edinburgh Hypoglycaemic Scale?

Answer 3

• 3.0mmol/l – autonomic (sweating, palpitations, shaking, hunger, may have no symptoms at this level)
• 2.5mmol/l – neuroglycopaenic (confusion, drowsiness, od behaviour, speech difficulty, incoordination)
• General malaise (headache, nausea)

Question 4

How is hypoglycaemia treated?

Answer 4

• Mild (4-7 dextrose tablets to get blood glucose above 4.0mmol)
• Moderate (if able treat as mild, if not give tubes of gluco/dextrogel to get blood glucose above 4.0mmol)
• Severe (ABCDE, stop IV insulin, give IV glucose 100mls 20% detrose or 150-200mls 10% glucose to get blood glucose above 4.0mmol)

Question 5

What are the DVLA requirements for diabetes?

Answer 5

• BM >5mmol/l before driving, carry CHO and identifiers
• If between 4-5mmol/l eat before driving
• 2hrs at a time
• Do not drive if feeling hypoglycaemic or BM <4mmol/l
• If hypoglycaemic give 45mins to 1hr before driving again
• Group 1 (no more than 1 severe hypo in 12 months, adequate hypoglycaemic awareness)
• Group 2 (no severe hypos in last 12 months, full hypoglycaemic awareness)

Question 6

What is the pathophysiology of DKA?

Answer 6

• Ketoacidosis
  
  • Insulin deficiency leads to increased lipolysis of adipose tissue, broken down to FFAs which go the liver and undergo ketogenesis and form ketone bodies (beta-hydroxybutyrate and acetoacetate).
  • This causes ketonemia/ketonuria as ketones are acidic and so increase the pH of the blood and urine.
• Dehydration
  
  • Osmotic diuresis as glucose in the urine draws water out with it.
• Potassium imbalance
  
  • Insulin drives potassium into cells but without insulin potassium cannot be stored in cells.
  • Serum concentration may be normal but total body potassium will be low.

Question 7

What are the clinical features of DKA?

Answer 7

• Plasma glucose <13.9mmol/l
• Urinary/plasma ketones ≥2+ urinary/>3mmol/L
• Metabolic acidosis
• Potassium imbalance
• Polyuria
• Polydipsia
• Nausea and vomiting
• Acetone smell to their breath
• Dehydration and subsequent hypotension
• Altered Consciousness

NB - Triggered by infection, intoxication, inappropriate withdrawal of insulin, infarction and intercurrent illness.

Question 8

How is DKA treated? (remember FIG-PICK)

Answer 8

• Diagnosis
  
  • Hyperglycaemia (i.e. blood glucose > 11 mmol/l)
  • Ketosis (i.e. blood ketones > 3 mmol/l)
  • Acidosis (i.e. pH < 7.3)
• Management (FIG-PICK) - refer to DKA pathway
  
  • Fluids – IV fluid resuscitation with normal saline (e.g. 1 litre stat, then 4 litres with added potassium over the next 12 hours)
  • Insulin – Add an insulin infusion (e.g. Actrapid at 0.1 Unit/kg/hour)
  • Glucose – Closely monitor blood glucose and add a dextrose infusion if below a certain level (e.g. 14 mmol/l)
  • Potassium – Closely monitor serum potassium (e.g. 4 hourly) and correct as required
  • Infection – Treat underlying triggers such as infection
  • Chart fluid balance
  • Ketones – Monitor blood ketones (or bicarbonate if ketone monitoring is unavailable)

NB - Establish the patient on their normal subcutaneous insulin regime prior to stopping the insulin and fluid infusion.

NB - Also remember children are at risk of cerebral oedema from fluid replacement so correct dehydration evenly over 48 hours - avoid fluid boluses. This will correct the dehydration and dilute the hyperglycaemia and the ketones. Correcting it faster increases the risk of cerebral oedema. Management options for cerebral oedema are slowing IV fluids, IV mannitol and IV hypertonic saline.

Question 9

What is the pathophysiology of hyperglycaemic hyperosmolar state (HHS)?

Answer 9

• Characterised by extreme elevations in serum glucose concentrations and hyperosmolality without significant ketosis.
• Measurable insulin concentration is believed to be sufficient to suppress lipolysis and ketogenesis but inadequate to regulate hepatic glucose production and promote glucose utilisation.
• Continued osmotic diuresis leads to hypernatraemia.
• This, alongside hyperglycaemia and inadequate water intake/increased water loss result in profound volume contraction.
• Hypovolaemia leads to progressive decline of GFR which aggravates the hyperglycaemic state.

Question 10

What are the clinical features of HHS?

Answer 10

• Hypovolaemia
• Very high blood glucose >30mmol/L
• Serum osmolality >320mOsmol/L (osmolality = 2x (Na+K)+Urea+Glucose
• Bicarbonate usually >15mmol/L
• Absence of significant ketones

Question 11

How is HHS treated?

Answer 11

• Treat the precipitant
• Fluids (0.9% NaCl, aim for 3-6L by 12hrs, switch to 0.45% NaCl if osmolality not falling dispite positive fluid balance, rate of Na fall should not exceed 10mmol in 24hrs)
• Insulin (rate of fall no more than 5mmol/L/hr, only start when glucose not falling with fluid alone, low dose insuling 0.05 units/kg/hr)
• Other (LMWH, foot protection)