Endocrine Abstracts

Introduction: In metformin-associated lactic acidosis with renal dysfunction inhibition of hepatic gluconeogenesis by drug accumulation may aggravate fasting induced-ketoacidosis. We report the occurrence of metformin-associated lactic acidosis with concurrent euglycemic ketoacidosis in three patients with renal failure.

Cases: The first patient was a 79-year-old woman who suffered from chronic kidney disease stage IIIa after traumatic uninephrectomy, and had been on metformin therapy for over 10 years. She had been vomiting for 2 days, and was admitted to our intensive care unit with acute renal failure (serum creatinine 9.0 mg/dl) and lactic acidosis (pH=6.89, lactic acid 22 mmol/l). The patient also displayed elevated serum ketoacids of 7.4 mmol/l at blood glucose level of 63 mg/dl. Euglycaemic ketoacidosis receded under treatment with intravenous glucose infusions.

The second patient was a 78-year-old woman who had been treated with metformin for T2DM and presented to our hospital with acute gastroenteritis. She displayed acute on chronic renal failure (serum creatinine 9.0 mg/dl) and lactic acidosis (pH=6.80, lactic acid 14.7 mmol/l). Again we detected elevated serum ketoacids (6.4 mmol/l), even though blood glucose was in normal range (76 mg/dl). Ketoacidosis abated after infusion of glucose.

The third patient was a 71-year-old man who had been treated with metformin, canagliflozin and liraglutide for T2DM and presented with acute gastroenteritis. He displayed acute renal failure (serum creatinine 13.6 mg/dl) and lactic acidosis (pH=7.21, lacitic acid 5.9 mmol/l). The patient also displayed elevated serum ketoacids of 16 mmol/l and blood glucose of 152 mg/dl. Ketoacidosis receded with intravenous glucose infusions.

Discussion: The concurrent occurrence of euglycaemic ketoacidosis in patients suffering from metformin-associated lactic acidosis poses a peculiar diagnostic and therapeutic challenge. This case series highlights the parallel occurrence of metformin-associated lactic acidosis and euglycemic ketoacidosis, the latter exceeding ketosis due to starvation, suggesting a metformin-triggered inhibition of gluconeogenesis. Affected patients benefit from glucose infusion counteracting suppressed hepatic gluconeogenesis.