Euglycemic ketoacidosis

Definition of diabetic ketoacidosis

  • Glucose > 14 mmol/L
  • Ketone bodies in urine or blood
  • Serum bicarb < 15 mmol/L

Euglycemic ketoacidosis requires the glucose to be normal (<11 mmol/L), or midly elevated.

  • Examples of ketoacidosis without insulin deficiency are alcoholic and starvation ketoacidosis.
  • Other possibilities include liver disorder or glycogen storage disorder.

Mechanism:

Ketone bodies formation are governed by a few factors

  • Insulin deficiency which leads to relative increase in glucagon and other stress hormones –> lipolysis to produce FFA as substrate for gluconeogenesis and ketone bodies synthesis
  • Starvation which leads to hypoglycemia –> increase in stress hormones –> lipolysis -> ketone bodies synthesis as body fuel
  • Excessive ethanol ingestion which leads to starvation (above) and metabolism into acetaldehyde which provides NADH for acetoacetate to be reduced to B-hydroxybutyrate
  • In glycogen storage disease or liver disease, glycogen storage is reduced –> in starvation state hypoglycemia can happen

– Note that diabetic patients could develop euglycemic ketoacidosis if they are starved but continue taking the insulin.
– Recently, use of SGLT2 inhibitors (glifozins) have also been proposed to be a mechanism of euglycemic ketoacidosis in diabetic patients.

  • Consider in diabetic patients taking SGLT2 inhibitors who present with abdo pain.
  • Mechanism: due to excessive glucosuria (which is not insulin dependant process) + insulin deficiency

NOT ALL KETOACIDOSIS IN DIABETES IS DKA !


Is it important to differentiate diabetic vs euglycemic ketoacidosis?

  • Yes, because treatment would differ somewhat.
  • In DKA, insulin+fluid would be the mainstay of the therapy. D5 is only required to maintain euglycemia.
  • In starvation or alcoholic ketoacidosis, patients are normally hypoglycemic, so hypoglycemia correction takes priority.
    – Once normal glucose level is restored, the body will shift from using ketone bodies to glucose as fuel.
    – Insulin is still needed as it promotes the conversion of acetoacetate to B-hydroxybutyrate which is then excreted in urine. D10 will be needed to faciliate the use of insulin in SKA/AKA.
  • Note that there can be a mixed of ketoacidosis due to insulin deficiency and starvation in diabetic patients.

Further management

  • Psychological management:
    – Find out why did they starve themselves? depression, anorexia etc
    – Also counselling for alcohol abuse problems if there is any.

Take home messages

  1. Euglycemic ketoacidosis: consider starvation, alcoholic or liver disease.
  2. Diabetic patients dont always have DIABETIC ketoacidosis. Consider starvation in state of insulin deficiency or use of SGLT2 inhibitors.
  3. Correction of hypoglycemia takes priority in treatment of euglycemic ketoacidosis. D10 maybe needed to facilitate the use of insulin.
  4. Psychological management: always ask why they starve/abuse alcohols ! As in DKA in which infection is the usual cause, depression/anorexia is common in patients with starvation ketoacidosis.

Reference:

Franklin Joseph1, Lydia Anderson1, Niru Goenka1, and Jiten Vora. Starvation-induced True Diabetic Euglycemic Ketoacidosis in Severe Depression. J Gen Intern Med 2008;24(1):129–31

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