High prevalence of mitochondrial diabetes mellitus in Japanese patients with major risk factors.

To identify diabetes mellitus caused by the mitochondrial gene substitution at genomic nucleotide pair 3243 (M3243A-->G) we selected 87 diabetic patients with high risk factors such as maternal inheritance and hearing loss. Total DNA was extracted from peripheral leukocytes, and mitochondrial DNA fragments containing M3243A-->G were amplified by polymerase chain reaction (PCR). The amplified fragments were digested with a restriction endonuclease Apa1 and analyzed by agarose gel electrophoresis. The incidence of the M3243A-->G mutation was 4.6% (four of 87) in diabetic patients with maternal inheritance and/or hearing loss. In a subgroup with both maternal inheritance and hearing loss, the incidence of the mutation was as high as 21.4% (three of 14). Cardiac disorders were also present in all four diabetic patients with the mutation. This study suggests that maternal inheritance and hearing loss are useful clinical findings to identify diabetic patients with the mutation, and that cardiac involvement is a high risk factor for the M3243A-->G mutation.