Background: Low-carbohydrate ketogenic diet (LCKD) has become increasingly popular over the past decades. We describe a case of LCKD-associated severe ketoacidosis in an adult with normal glucose metabolism.
Case: A 37-year-old woman with a BMI of 28.0kg/m2 presented with three days of persistent vomiting and epigastric pain without symptomatic hyperglycaemia. She had started on a LCKD with ketone supplements for weight loss two weeks prior, with an estimated daily carbohydrate intake of <20g. She had no history of diabetes, took no regular medications and reported no alcohol consumption or toxin ingestion. She had a previous history of anorexia nervosa with a nadir weight of 27 kg. Investigations revealed severe ketoacidosis: pH, 7.09; pCO2, 19mmHg; bicarbonate, 6mmol/L; point-of-care ketone, 7.0mmol/L; glucose, 23.2mmol/L; anion gap 39mmol/L; and lactate, 3.7mmol/L. She was treated for presumed diabetic ketoacidosis with insulin and glucose infusion, achieving swift biochemical resolution. HbA1c was normal, with no beta-cell dysfunction or autoimmunity. She remained euglycaemic without any glucose-lowering therapy. The patient was discharged with dietary advice to avoid LCKD and ketone supplements.
Discussion: LCKD induces ketosis via various mechanisms. In carbohydrate-rich states, citrate produced by glycolysis inhibits carnitine palmitoyltransferase complex-1 (CPT-1), limiting the beta-oxidation of fatty acids and thereby reducing ketogenesis.1 However, the opposite occurs in low-carbohydrate states. LCKD enhances alpha cell secretion of glucagon and lower insulin concentrations, resulting in a high glucagon-to-insulin ratio which promotes ketosis. Lactate—which increases during starvation—induces hepatic ketogenesis. The ketotic state progresses to ketoacidosis once usual physiologic-buffering mechanisms are exceeded (figure). Carbohydrate-restricted ketogenic diet stimulates release of counterregulatory hormones, promoting hepatic gluconeogenesis and glycogenolysis and subsequent hyperglycaemia.2,3 Severe carbohydrate-restricted diets with ketone supplements may induce ketoacidosis with hyperglycaemia in predisposed individuals, highlighting the importance of taking a detailed dietary history during an atypical presentation of what is thought to be diabetic ketoacidosis.