Combined Glucose and Thiamine Treatment for Sepsis

The current consensus model of sepsis is that it is a dysregulated host response to infection associated with severe organ dysfunction and failure. In 2023 the author proposed a new model of sepsis in that it was a physiological response and defence to infection that failed or became “dysregulated” particularly if the infection was overwhelming or there was a deficiency of thiamine and/or intracellular glucose to provide ongoing fuel for the immune response and/or mitochondrial production of adenosine triphosphate (ATP).This new model proposed that during sepsis, the immune system received priority access to available glucose, prompting insulin resistance that minimised glucose utilisation by less essential tissues. Concurrently, mitochondrial ATP production via oxidative phosphorylation (OXPHOS) was deprioritised, with the immune system relying on anaerobic glycolysis for ATP generation. This suppression of OXPHOS was only a temporary measure; mitochondrial ATP production had to be resumed for complete recovery. Its persistent suppression could culminate in critical ATP deficits and cell death.This paper reviews the consensus model of sepsis and evidence for the new model.It also reviews glucose, thiamine and insulin metabolism in sepsis and concludes that administering high-dose insulin alongside mild hyperglycaemia and intravenous thiamine—a pyruvate dehydrogenase kinase (PDK) inhibitor—may help restore physiological mitochondrial ATP production when administered during a crucial window in the sepsis process, potentially improving survival outcomes.The thrust of this new model may have been validated by a recent experiment on sepsis in mice that found superior survival following treatment with combined glucose and thiamine compared to antibiotics.