Diabetic ketoacidosis

Pathophysiology

• Caused by a relative lack of insulin; leading to high levels of glucagon, cortisol, and adrenaline; that stimulates lipolysis; leading to increased circulating free fatty acids, which are directed to the ketogenesis pathway in the liver
• Can occur in T2DM when patients are relatively insulin-deficient and there is intercurrent illness and dehydration which stimulates counter-regulatory hormone secretion (especially glucagon)
• Correction of hypovolaemia will often improve acidosis and hyperglycaemia, along with insulin infusion
• Abdominal pain is present in 46% of patients with DKA, but uncommon in HHS. It can be caused by ileus, gastroparesis and electrolyte abnormalities. Seek alternative aetiologies such as pancreatitis if pain persists after correction of DKA.

Triggers

• Non-compliance
• Infection
• Trauma
• Pregnancy
• Infarction
• Cocaine

Presentation

• Nausea/vomiting, thirst, dyspnoea
• Tachycardia, dehydration/hypotension, tachypnoea, abdominal tenderness, lethargy/obtundation/cerebral oedema/coma

Diagnosis

• Triad of hyperglycaemia, ketonaemia, and high anion gap metabolic acidosis (usually the major finding)
• Euglycaemic DKA can occur in starvation, pregnancy, pre-treatment with insulin, or SGLT-2 inhibitors

	DKA			HHS
	Mild	Moderate	Severe
Plasma glucose (mmol/L)	>13.9	>13.9	>13.9	>33.3
Arterial pH	7.25 to 7.30	7.00 to 7.24	<7.00	>7.30
Serum bicarbonate (mEq/L)	15 to 18	10 to <15	<10	>18
Urine ketones¶	Positive	Positive	Positive	Small
Serum ketones – Nitroprusside reaction	Positive	Positive	Positive	≤ Small
Serum ketones – Enzymatic assay of beta hydroxybutyrate (normal range <0.6 mmol/L)Δ	3 to 4 mmol/L	4 to 8 mmol/L	>8 mmol/L	<0.6 mmol/L
Effective serum osmolality (mOsm/kg)◊	Variable	Variable	Variable	>320
Anion gap§	>10	>12	>12	Variable
Alteration in sensoria or mental obtundation	Alert	Alert/drowsy	Stupor/coma	Stupor/coma

Differential diagnosis

• Alcoholic ketoacidosis: ketoacidosis without hyperglycaemia in a patient with chronic alcoholism is virtually diagnostic of AKA
• Fasting ketoacidosis: ketones usually only mildly elevated, with serum bicarb usually >17
• Other causes of anion-gap acidosis
• Euglycaemic DKA secondary to SGLT-2 inhibitors
  • See separate topic under 'peri-op diabetes'

Management

Resuscitate

• • 2-3L of 0.9% N/S over 1-3 hours, then run at 250ml/hr
  • Change to 5% dextrose at 150-250ml/hr when BSL < 13.9
  • K+ > 3.3
  • Review triggers, identify cause

Insulin infusion

• • Bolus of 0.1 U/kg IV short-acting insulin given immediately
  • 0.1 U/kg/hr by continuous infusion (once potassium ok)
  • Increase 2-3x if no response by 4 hours
  • Measure BSL hourly
  • VBG q4h, especially for K+
  • Cease when the patient is stable, BSL 8.3-11.1, and acidosis is resolved
  • Give long-acting insulin as soon as the patient is eating, then remove the insulin infusion 2-4 hours later