Effects of chlorpropamide and alcohol on aldehyde dehydrogenase activity and blood acetaldehyde concentration

Aldehyde dehydrogenase (ALDH) activity is increased in Type 2 diabetics with macrovascular disease, and is a critical factor determining the chlorpropamide-alcohol flush (CPAF), a phenomenon possibly related to diabetic complications. To evaluate the possible effects of chlorpropamide (CP) on ALDH activity we studied 8 Type 1 and 20 Type 2 diabetics. Blood acetaldehyde concentration after intake of CP and alcohol was higher in patients with CPAF than in those without CPAF (p less than 0.005), and in those with low basal erythrocyte ALDH activity than in those with high basal enzyme activity (p less than 0.05). Administration of CP reduced ALDH activity in 20 of 26 patients (p less than 0.05). Alcohol intake was observed to have an additional inhibitory effect on ALDH activity. Accordingly, a combination of CP and alcohol decreases the activity of erythrocyte ALDH which might explain the CPAF phenomenon. Absent correlation between CP level and reduction of ALDH activity indicates a major role for alcohol in CPAF. A therapeutic dose of CP or a small amount of alcohol might be used when a reduction of ALDH activity is considered.