ALDH 2 Gene Mutation and Glycemic Control in Type-2 Diabetes

The mitochondrial enzyme aldehyde dehydrogenase 2 (ALDH 2) plays the major role in acetaldehyde detoxification after alcohol ingestion. To determine the gene effect on the glycemic state, we investigated the ALDH 2 genotype in 163 male type-2 diabetes patients randomly screened in our out-patient clinic. Female patients were excluded because few were in the habit of consuming alcohol. The results showed that in the group of alcohol drinkers the HbA1C level in the inactive ALDH 2 group (8.1 ± 1.3 n=38) was higher than in the active ALDH 2 group (7.5 ± 0.9 n=70) (p=0.017, student's t test), suggesting the deleterious effect of ALDH 2 mutation on glycemic control in diabetes. We speculate that, acetaldehyde accumulation in patients with inactive ALDH 2 worsens hyperglycemia, because acetaldehyde reduces glucose-induced insulin secretion by β-cell and inhibits insulin action.