Can Adrenaline Cause Euglycemic DKA?
Yes, adrenaline (epinephrine) can precipitate diabetic ketoacidosis, including euglycemic DKA, in patients with diabetes through direct suppression of insulin secretion, stimulation of lipolysis, and promotion of ketone body generation.
Mechanism of Epinephrine-Induced DKA
Epinephrine has multiple metabolic effects that can trigger ketoacidosis:
- Epinephrine increases glycogenolysis, reduces glucose uptake by tissues, and inhibits insulin release in the pancreas, resulting in hyperglycemia and increased blood lactic acid 1
- Epinephrine directly suppresses insulin secretion, stimulates lipolysis, and causes ketone body generation, creating the metabolic conditions necessary for DKA 2
- Sympathomimetic agents (including epinephrine, dobutamine, and terbutaline) are recognized precipitating factors that may trigger the development of DKA 3
Clinical Evidence and Case Reports
The risk is documented in real-world clinical scenarios:
- A case report demonstrated diabetic ketoacidosis in a young woman precipitated by epinephrine administration for anaphylaxis treatment, despite the patient having evidence of ongoing endogenous insulin production and having received long-acting insulin less than 24 hours prior 2
- High-dose catecholamine administration can cause unexpected diabetic ketoacidosis in patients with risk factors, and early administration of insulin may not protect patients from developing ketoacidosis in the setting of high-dose catecholamine administration 2
Euglycemic DKA Considerations
Epinephrine can contribute to euglycemic presentations:
- Euglycemic DKA is defined as ketoacidosis with blood glucose levels less than 200 mg/dL, despite meeting other DKA criteria (pH <7.3, bicarbonate <15 mEq/L, and ketosis) 4
- The combination of insulin deficiency and increased counter-regulatory hormones (including catecholamines) characterizes the metabolic derangements in DKA 5, 6
- Epinephrine's insulin-suppressing effects combined with its promotion of ketogenesis can create ketoacidosis even when glucose levels remain relatively normal 2
Clinical Implications and Risk Factors
The risk of diabetic ketoacidosis should be considered when administering epinephrine to patients with diabetes, even in the absence of complete insulin deficiency 2:
- Patients with diabetes and poor glycemic control are at highest risk 2
- The risk exists even in patients with type 2 diabetes under stressful conditions 7, 6
- Drugs affecting carbohydrate metabolism, including sympathomimetic agents, are established precipitating factors for both DKA and hyperosmolar hyperglycemic state 3
Critical Pitfalls to Avoid
- Don't assume that recent insulin administration protects against epinephrine-induced DKA—ketoacidosis can develop despite adequate baseline insulin coverage 2
- Don't overlook DKA in patients presenting with normal or near-normal glucose levels after epinephrine administration—check serum ketones and pH in any diabetic patient receiving catecholamines who develops symptoms 4
- Don't dismiss the possibility of infection as a co-precipitant, as patients can be normothermic or even hypothermic despite serious infection 3
Monitoring Recommendations
For diabetic patients receiving epinephrine:
- Monitor blood glucose, serum ketones (preferably β-hydroxybutyrate), and electrolytes closely 8, 9
- Maintain high clinical suspicion for DKA development, particularly with high-dose or prolonged catecholamine administration 2
- Consider early insulin therapy and dextrose-containing fluids if ketosis develops, as both insulin and glucose are needed to resolve ketonuria 9