Ethanol can cause hypoglycaemia when taken in combination with fasting or physical exercise (1). If no insulin has been administered, other causes may be endogen hyperinsulinemia, peroral antidiabetics, trimethoprim sulfa, beta blockers, antiarrhythmics, adrenal gland failure, sepsis and liver failure (2).
One study found that 4 % of ethanol intoxicated patients suffered from hypoglycaemia (3). The same study referred to another American study which suggested that 14 % of 1,418 drug and alcohol-induced episodes of hypoglycaemia were caused by ethanol (2). These percentages may well be too high. Others have found an incidence of 0.9 % (4). Of 2,348 patients treated for acute poisoning in Oslo, 21 suffered from hypoglycaemia. Ethanol was the agent in 1,018 of these cases, but no potential correlation was discussed (5). A large university hospital in New York found that ethanol was the cause in 45 of 125 patients admitted with hypoglycaemia. Hospitalisation was necessary in 31 of the 45 cases (6).
However, another study has shown that the blood alcohol concentration of approximately half the patients with ethanol-induced hypoglycaemia may be so low at the time of testing that many are excluded from the statistics; the incidence is therefore similarly uncertain (7). The same authors maintain that alcohol-induced hypoglycaemia has received much less attention in Europe than in the USA (7).
In children, even small amounts of unintentionally administered or ingested ethanol will result in hypoglycaemia. Hypoglycaemia has been described after the washing of feverous skin with alcohol, and after ingestion of alcohol-containing mouthwash (7). In small case report studies, the hypoglycaemia incidence in children intoxicated by ethanol has been stipulated to between 10 % and 24 % (8), while another retrospective study found an incidence of 3.4 % (9). Again, it is difficult to compare these studies, since by the time the patients have been admitted to hospital their ethanol concentration may have fallen to a level below that which would suggest ethanol as the cause of the hypoglycaemia.
In adults, the dominating combination is one of depleted glycogen stores and ethanol ingestion (2). It is probable that this combination also features prominently in young children, whose glycogen stores empty much faster than in adults.
In adults, glycogen stores can be depleted after approx. 12 hours of fasting, but considerably sooner with increased consumption, as in the case of strenuous physical exercise. Our patient had been cross-country skiing for seven hours, a physically demanding hike involving a lot of up-hill climbing and down-hill snowboarding.
The mechanism has been known for a long time. Ethanol inhibits the gluconeogenesis (1). For the alcohol dehydrogenase enzyme in the liver cells to be able to convert ethanol, an array of electron transport molecules is required, as well as the coenzyme nicotinamide adenine dinucleotide (NAD+). As long as there is ethanol to be metabolised, the reduced NADH (nicotinamide adenine dinucleotide)/NAD+ ratio will be considerably raised. Consequently, there is insufficient NAD+ available for other reactions, such as in the gluconeogenesis.
One of the roles of NAD+ is to be used by the lactate dehydrogenase enzyme for the conversion of lactate to pyruvate. If the NAD+ level is low, the pyruvate concentration will fall and the formation of sugar from pyruvate will be impaired to the extent that the blood glucose level falls. The use of fat and amino acids in the gluconeogenesis also requires NAD+, and this process becomes less effective when the ethanol conversion appropriates so much of this coenzyme (10). This mechanism works even at low ethanol concentrations (fig 1). In animal studies, 47 % of the gluconeogenesis is inhibited at a blood ethanol concentration of 0.1 (11). This matches the findings of a more recent study of five healthy male volunteers, whose gluconeogenesis was reduced by 45 % (12).
Another mechanism that may result in hypoglycaemia is that ethanol also increases the level of a substance that inhibits the reading of a number of genes that are of particular importance to the gluconeogenesis (13). A third cause is that ethanol increases the circulation of blood through the islets of Langerhans in the pancreas, at the expense of the exocrine part, which may lead to increased insulin secretion (14). We are not aware of anyone having attempted to identify which of these factors is the greatest contributor to alcohol-induced hypoglycaemia.
Our patient’s lactic acidosis was striking with readings that are normally encountered only in cases of serious septic shock or other serious circulation failure. Such patients generally suffer from tissue hypoperfusion, which results in type A lactic acidosis. Any lactic acidosis which is not caused by tissue hypoperfusion is referred to as type B lactic acidosis, and is often caused by deficient intracellular conversion of lactate. Type B lactic acidosis also occurs in connection with Metformin treatment, vitamin B1 deficiency and malign hematologic diseases (15). Alcohol-induced hypoglycaemia is yet another example of a type B lactic acidosis. If there is insufficient NAD+, the lactate dehydrogenase enzyme will not be able to convert lactate to pyruvate fast enough, thus resulting in lactate accumulation (1).
Because the lactate levels were measured on a small acid-base apparatus, it may have been the glycolic acid level that was measured, because these devices incorrectly interpret glycolic acid as lactate. Although we have previously discussed this «lactic gap», ethylene glycol poisoning did not form part of this patient’s assessment (16). Methanol poisoning should also be considered in metabolic acidosis patients intoxicated by alcohol.
So far, we have been talking exclusively about ethanol-induced hypoglycaemia. It is an interesting question whether intoxication from other types of alcohol, e.g. ethylene glycol or methanol, will also appropriate NAD+, inhibit the gluconeogenesis and induce hypoglycaemia while causing lactic acidosis. If so, this is yet another matter for consideration when exploring metabolic acid-base imbalance, which is often difficult (16).
Several of the American articles on alcohol-induced hypoglycaemia assume that the condition is often not acknowledged, and may therefore be underreported (3, 7). Although our patient’s combination of fasting, vodka and a long cross-country skiing hike cannot be considered a common combination, it is nevertheless not uncommon for alcohol consumption to be accompanied by minimal or no consumption of food. Perhaps hypoglycaemia is the root cause of more instances of atypical intoxication, aggression and impaired consciousness than reported?
The ABC acronym of emergency medicine is well known. For some, its continuation – DEFG – Dont Ever Forget Glucose – has been an equally important mnemonic, ensuring that blood sugar measurements are never forgotten about for patients with reduced consciousness. It is easy to overlook this simple test, particularly when there are obvious factors that more readily present themselves as probable causes. We now know that the combination of fasting and alcohol may cause serious hypoglycaemia with cerebral symptoms, which should never be confused with alcohol intoxication.
It is therefore always important to establish whether hypoglycaemia is the cause of any consciousness impairment.