Abstract
In 1978, Pyke and Leslie (1,2) first proposed the hypothesis that clinical pictures of patients with type 2 diabetes can be characterized by two clinical presentations in response to chlorpropamide use and tolerance to alcohol. Chlorpropamide alcohol flushing (CPAF) is often observed in diabetic patients with a family history of diabetes, but among those patients without CPAF, there is a high probability of developing severe diabetic retinopathy. Subsequently, Barnett et al. (3) has reported that persistent proteinuria is also more commonly observed in patients without CPAF. However, the role and significance of CPAF and diabetic vasculopathy still remains controversial. Aldehyde dehydrogenase-2 (ALDH2) and alcohol dehydrogenase-2 (ADH2) are the key enzymes for alcohol metabolism. Many Asians lack enzyme activity of ALDH2 and have superactive enzyme activity of ADH2, attributed to point mutations within both structural genes (4). Hence, the expression of these two enzyme mutations could determine the alcohol tolerance among the Japanese population. We have found an increase in the prevalence of nephropathy and advanced diabetic retinopathy among Japanese patients with diabetes and a specific ADH2 and ALDH2 genotype. …
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