A 68-year-old homeless man with a history of hospitalization for alcohol intoxication is brought in confused. His serum glucose is 39mg/dl. Which of the following is likely true?
1.He has also been using cocaine
2.He has decreased activity of alcohol dehydrogenase
3.hepatic gluconeogenesis is elevated
4.The next step in management is glucose repletion
5.His hepatic NADH/NAD+ratio is high
The metabolism of alcohol involves the generation of NADH, leading to a high NADH/NAD+ ratio.
Alcohol metabolism is a two-step process involving the transformation of alcohol to acetaldehyde (catalyzed by alcohol dehydrogenase, and then subsequent conversion of the acetaldehyde to acetic acid by aldehyde dehydrogenase. Both of the these reactions are oxidation reactions and result in the generation of NADH, leading to an elevated NADH/NAD+ level. The elevated NADH/NAD+ ratio favors glycolytic reactions and decreased hepatic gluconeogenesis, contributing to the hypoglycemia that chronic alcohol users are often found to have.
Le and Bhushan review the mechanism of hypoglycemia after ethanol ingestion. They note that ethanol metabolism leads to an elevated NADH/NAD+ ratio which diverts pyruvate to lactate and oxaloacetate to malate. This leads to inhibited gluconeogenesis and the stimulation of fatty acid synthesis. The lactate production leads to lactic acidosis and the depletion of oxaloacetate shuts down the Kreb’s cycle.
Vatsalya et al. conducted a trial to examine the effects of intravenous alcohol on the growth-hormone-insulin-like growth factor-1 axis and gonadal hormones. Forty-eight volunteers were exposed to an infusion of alcohol and their blood was drawn post infusion to check for GH, IGF-1, free testosterone, and estradiol. They found that there was significant alcohol-induced suppression of testosterone in men, and there was alcohol-induced increases in estradiol in women. They found a trend for decreasing IGF-1 levels and a significant alcohol-induced GH decrease for individuals with high baseline GH levels. Men had significantly greater changes in GH compared with women.
Illustration A is a diagram of the metabolic steps involved in breaking down alcohol.