Lactic Acidosis and Hypoglycemia in Diabetes

Causes of Lactic Acidosis

The American Diabetes Association recommends considering SGLT2 inhibitors as a cause of euglycemic diabetic ketoacidosis with associated lactic acidosis in patients with diabetes 1
The National Kidney Foundation suggests that renal failure can impair both lactate clearance and gluconeogenesis, contributing to lactic acidosis 2
Liver failure can precipitate euglycemic diabetic ketoacidosis with lactic acidosis, according to the American Association of Clinical Endocrinologists 1

The American Journal of Kidney Diseases states that sulfonylureas or active metabolites accumulating in renal impairment can cause hypoglycemia 2
The National Kidney Foundation recommends avoiding first-generation sulfonylureas entirely in patients with chronic kidney disease (CKD) due to the risk of hypoglycemia 2
Nateglinide accumulates with decreased kidney function, increasing the risk of hypoglycemia, as reported by the American Journal of Kidney Diseases 2

The Genetics in Medicine journal reports that glucose-6-phosphatase deficiency (Type Ia) or glucose-6-phosphate transporter deficiency (Type Ib) can cause hypoglycemia and lactic acidosis in patients with glycogen storage disease type I (GSD I) 3, 4, 5
Fructose-1,6-bisphosphatase deficiency can cause hypoglycemia after prolonged fasting with reduced carbohydrate intake, according to the Genetics in Medicine journal 4, 6

The American Diabetes Association recommends considering euglycemic diabetic ketoacidosis (glucose <200 mg/dL) in patients with insulin deficiency, reduced food intake, pregnancy, alcohol use, liver failure, or SGLT2 inhibitor therapy 1
The Diabetes Care journal states that nausea and vomiting with hyperglycemia may indicate diabetic ketoacidosis (DKA), a life-threatening emergency requiring immediate medical care 7
Mixed acid-base disturbances can complicate diagnosis, particularly in pregnancy with hyperemesis, as reported by the Diabetes Care journal 1

The Genetics in Medicine journal recommends never performing glucagon stimulation testing in suspected GSD I as it worsens metabolic acidosis and causes acute decompensation 4, 6
The Praxis Medical Insights journal suggests stopping SGLT2 inhibitors immediately if DKA is suspected, as they increase euglycemic DKA risk 8

SGLT2‑inhibitor therapy, hepatic failure, pregnancy, alcohol consumption, and reduced oral intake can trigger euglycemic diabetic ketoacidosis (glucose < 200 mg/dL) with concurrent lactic acidosis in patients with insulin deficiency. 9

Clinicians should maintain a high index of suspicion for euglycemic DKA in individuals taking SGLT2 inhibitors, those with limited food intake, or pregnant patients who present with nausea, vomiting, metabolic acidosis, and a blood glucose level below 200 mg/dL. 9

Standard DKA treatment protocols—including continuous insulin infusion, appropriate fluid resuscitation, and electrolyte monitoring—should be applied in euglycemic DKA despite the lower glucose concentrations. 9, 10

Approximately 50 % of patients receiving therapy for hyperglycemic crises develop hypokalaemia; severe hypokalaemia (serum K⁺ < 2.5 mmol/L) is linked to increased mortality and therefore mandates vigilant potassium monitoring and replacement. 10