(18.03) Hyper Warburg Effect and Hypoglycemia

In the 1920’s Warburg and Cori described how cancer cells’ energy generation is different from that of normal cells.  They observed high glucose consumption and large amount of lactate excretion from cancer cells compared with normal cells which oxidize glucose utilizing mitochondria.  At that time, it was assumed that the cancer cells were generating energy using glycolysis rather than mitochondrial oxidative phosphorylation. Differing tumor types have different alterations to meet their high energy requirements.  The Warburg effect is the increased uptake of glucose with lactic acid production in cancer cells in states of oxygen (1). There is an upregulation of major glycolytic enzymes.  The upregulation of hexokinase activity catalyzes the phosphorylation of glucose to glucose-6-phosphate in glycolysis. There is CNS reliance on lactate for energy instead of glucose. 

Case(s) Description :

We report a 79-year-old male who was in his normal state of health until 1/2021 when he became fatigued, weak, had abdominal pain, and started to lose weight.  He was found to have elevated liver function tests and abdominal lymphadenopathy on an outside CT scan and underwent excisional lymph node biopsy revealing mantle cell lymphoma.  Flow cytometry showed monoclonal kappa B cell population with aberrant CD5 expression. 
He continued with abdominal pain and presented to the Emergency Department.  Once abdominal pain improved, his hypoglycemia continued.  Blood sugars ranged from 51 mg/dL-max of 96 mg/dL.  Lactate level was 16 mmol/l and increased to 26 mmol/l. He was started on a clinical trial for treatment of his mantle cell lymphoma and his lactate improved.  He continued to have hypoglycemia despite attempts to increase glucose uptake.  The patient was asymptomatic and lacked any neuroglycopenic symptoms. As his primary cancer improved, his lactate decreased.  When his lactate decreased to 4.7 mmol/l--3 months later, his glucose level normalized.  His PET CT during the time of hypoglycemia and high lactate showed no physiologic brain uptake while repeat PET CT 3 months later showed normal physiologic uptake in the brain. This PET scan supports the hypothesis that lactate served as a fuel for the brain, thus protecting against hypoglycemia.

Discussion : This along with his clinical picture display an exaggerated Warburg effect or “hyper-Warburgism”.