Euglycaemic ketoacidosis from an SGLT2 inhibitor exacerbated by a ketogenic diet

To the Editor: A 64‐year‐old woman presented to our emergency department with progressively reduced consciousness over 3 days. This was preceded by 2 days of vomiting and diarrhoea. She had been systemically well before this, with no acute medical issues. She had type 2 diabetes and had been commenced on combination 10 mg empagliflozin and 5 mg linagliptin a year ago after having experienced diarrhoea with metformin. Her most recent glycated haemoglobin level was 58 mmol/mol (reference interval [RI], 20–42 mmol/mol). She had also been trialling the Atkins diet for about 2 months before presentation.

Her initial blood tests demonstrated high anion gap metabolic acidosis, an initial blood sugar level of 10.3 mmol/L (RI, 3.2–5.4 mmol/L] and a serum ketone level of 4.7 mmol/L (RI, < 0.6 mmol/L). She was diagnosed as having euglycaemic ketoacidosis secondary to using a sodium–glucose cotransporter type 2 (SGLT2) inhibitor (empagliflozin) and precipitated by her diarrhoeal illness and her Atkins diet. After a dextrose and insulin infusion, the anion gap normalised within 4 hours of presentation. She became progressively more alert within 24 hours of presentation. She was discharged 2 days after presentation with directions never to recommence empagliflozin.

This case highlights the risks of combining ketogenic diets such as the Atkins diet with SGLT2 inhibitors, as outlined by Grammatiki and colleagues.1 SGLT2 inhibitors have a diuretic effect as they block the reabsorption of sodium as well as glucose.2 Hypovolaemia stimulates release of counter‐regulatory hormones such as glucagon, cortisol and adrenaline, which further increase insulin resistance, lipolysis and ketogenesis.

Our patient's diarrhoeal illness preceding presentation likely exacerbated this hypovolaemia and therefore ketogenesis. High protein, low carbohydrate ketogenic diets such as Atkins in isolation usually only result in a mild, temporary ketosis.3 In the setting of an SGLT2 inhibitor and infective illness, however, it increased our patient's susceptibility to ketosis.