(3.01) Persistent lactic acidosis following the resolution of diabetic ketoacidosis (DKA) in a young individual with poorly managed Type 1 Diabetes Mellitus (T1DM)

Lactic acidosis (LA) is frequently observed in critically ill patients. In patients with diabetic ketoacidosis (DKA), multiple pathophysiological mechanisms are accountable for the elevated lactate concentrations. The precise mechanism is uncertain, but the compromised tissue perfusion due to hypovolemia, an epinephrine-driven response due to insulin insufficiency, the impact of stress status, and glycogenic hepatopathy (GH) are involved. GH can cause lactic acidosis, a rare condition due to excessive glycogen accumulation in the hepatocytes, and also an uncommon complication from poorly managed diabetes mellitus (DM), characterized by hepatomegaly and temporary elevation in serum aminotransferase enzyme levels. The diagnosis is challenging, as it necessitates excluding other conditions, e.g., metabolic dysfunction-associated steatohepatitis (MASH). GH is more prevalent in young individuals with poorly controlled T1DM. In contrast, MASH is frequently observed in obese individuals with type 2 diabetes.

Case(s) Description : A 28-year-old female with a history of uncontrolled T1DM was diagnosed a decade ago. HbA1c was 10.8, and her BMI was 21.43. Over the past 6 months, she experienced 3 admissions to the Intensive Care Unit (ICU) due to DKA. She was noncompliant with treatment due to low health literacy. She frequently practiced fasting and consumed low-quality food. Her average blood glucose (BG) at home was 200 mg/dL. Her initial laboratory findings indicated an anion gap of 33, bicarbonate levels at 5 mEq/L, a BG of 540 mg/dL, B-hydroxybutyrate at 8.7 mmol/L, and lactic acid at 9.6 mmol/L. Liver function tests were unremarkable. DKA was successfully resolved within 7 hours. However, her ICU stay was prolonged due to the persistent elevation of lactic acid levels for 6 days. Liver enzyme levels escalated to AST 360 and ALT 69 after the resolution of DKA. An abdominal ultrasound (US) examination revealed hepatomegaly, with the liver measuring 22 cm in size and displaying normal echogenicity. A liver biopsy to confirm the diagnosis of GH was not performed. Sepsis was ruled out. Importantly, it was observed that lactic acid levels increased once BG dropped below 200 mg/dL. Conversely, lactic acid levels decreased when the BG exceeded 200 mg/dL.

Discussion : The atypical correlation between BG and lactic acid levels merits attention. The patient received continuous insulin infusion at a fixed dose of 2 units/hour and a 5% dextrose infusion for 3 days, in conjunction with SQ insulin. This treatment improved lactic acid and liver enzyme levels by the end of her hospitalization. GH should be considered a potential diagnosis in individuals with poorly managed T1DM, often intertwined with inadequate health literacy, who exhibit heightened liver enzyme levels, hepatomegaly, and ongoing lactic acidosis even after DKA has been resolved. A few cases in the literature have reported similar findings.  Diagnosing GH can be challenging since the definitive diagnosis of GH is established through biopsy. It is crucial to differentiate GH from MASH, as GH does not progress to cirrhosis and is a reversible condition achievable through strict glucose control.