A Patient with Acute Liver Failure and Extreme Hypoglycaemia with Lactic Acidosis who was not in Coma: Causes and Consequences of Lactate-Protected Hypoglycaemia

Abstract

Lactate can substitute for glucose as a metabolic substrate. We report a patient with acute liver failure who was awake despite a glucose level of 0.7 mmol/l with very high lactate level of 25 mmol/l. The hypoglycaemia+hyperlactataemia combination may be considered paradoxical since glucose is the main precursor of lactate and lactate is reconverted into glucose by the Cori cycle. Literature relevant to the underlying mechanism of combined deep hypoglycaemia and severe hyperlactataemia was assessed. We also assessed the literature for evidence of protection against deep hypoglycaemia by hyperlactataemia. Four syndromes demonstrating hypoglycaemia+hyperlactataemia were found: 1) paracetamol-induced acute liver failure, 2) severe malaria, 3) lymphoma and 4) glucose-6-phosphatase deficiency. An impaired Cori cycle is a key component in all of these metabolic states. Apparently the liver, after exhausting its glycogen stores, loses the gluconeogenic pathway to generate glucose and thereby its ability to remove lactate as well. Several patients with lactic acidosis and glucose levels below 1.7 mmol/l who were not in a coma have been reported. These observations and other data coherently indicate that lactate-protected hypoglycaemia is, at least transiently, a viable state under experimental and clinical conditions. Severe hypoglycaemia+hyperlactataemia reflects failure of the gluconeogenic pathway of lactate metabolism. The existence of lactate-protected hypoglycaemia implies that patients who present with this metabolic state should not automatically be considered to have sustained irreversible brain damage. Moreover, therapies that aim to achieve hypoglycaemia might be feasible with concomitant hyperlactataemia.

Retrospective evaluation of the association between admission blood glucose and l‐lactate concentrations in ponies and horses with gastrointestinal disease (2008‐2016): 545 cases

“…This association was independent of BG concentrations, although BG concentrations were also significantly associated with l ‐lactate concentrations. As the close correlation between the 2 parameters highlights, BG and L‐lactate concentrations are interconnected metabolites in the carbohydrate metabolism and each can lead to the generation of the other . Anaerobic glycolysis of glucose generates l ‐lactate as an end product while l ‐lactate, via generation of pyruvate, can initiate gluconeogenesis or glycogen formation .…”

“…As the close correlation between the 2 parameters highlights, BG and L-lactate concentrations are interconnected metabolites in the carbohydrate metabolism and each can lead to the generation of the other. 11,12 Anaerobic glycolysis of glucose generates L-lactate as an end product while L-lactate, via generation of pyruvate, can initiate gluconeogenesis or glycogen formation. 13 In septic human patients, 45% of L-lactate is converted into glucose either by gluconeogenesis or glycogen production.…”

The association of early combined lactate and glucose levels with subsequent renal and liver dysfunction and hospital mortality in critically ill patients

“…Lactate levels have been shown to be significantly higher in patients with early hepatic dysfunction in the setting of acute circulatory failure [ 31 ] and the a priori presence of liver dysfunction as defined by previous medical history or initial laboratory measurements at presentation is significantly associated with impaired lactate normalization during resuscitation of severe sepsis and septic shock [ 32 ]. During acute liver failure, such as after paracetamol intoxication, gluconeogenesis can be extremely impaired with very elevated lactate levels (>20 mmol/L) and deep hypoglycemia (<1 mmol/L) [ 33 ]. Our study showed that patients with discrepantly elevated lactate and decreased glucose subsequently developed higher bilirubin levels and liver enzymes (Additional file 2 : Figures S11 and S12) compared to patients with elevations of both lactate and glucose.…”

Oral lactate intensifies insulin toxicity during severe insulin-induced hypoglycemia in mice

“…When coupled with results from our previous study (Hartman et al, 2010;Rodrigues et al, 2011), this new concept concerning the role of lactate as a brain fuel (Pellerin, Magistretti, 2012;Proia et al, 2016;Smith et al, 2003), suggests the possibility of using lactate rather than glucose to treat insulin induced hypoglycemia (Chan et al, 2013;De Feyter et al, 2013;Herzog et al, 2013;Oldenbeuving et al, 2014;Rooijackers et al, 2016).…”