A Screening Approach for Mitochondrial tRNALeu(UUR) A3243G Mutation in a Hospital-Based Population with Diabetes

To the Editor: Diabetes caused by mitochondrial tRNALeu(UUR) A3243G mutation is one of the most common types of mitochondrial diabetes mellitus (MDM). Seventeen years ago, we reported that the prevalence of MDM was 0.4% in clinically diagnosed type 2 diabetes mellitus (T2DM) patients (n = 716).[1] Recently, we reviewed all the studies reporting MDM cases from grade three and first‐class hospitals in China (unpublished) and found that the prevalence of MDM in a pooled randomly selected T2DM population was 0.64%. MDM patients are usually characterized by early age at diagnosis, low beta‐cell function, and lack of obesity, insulin resistance, and autoantibodies associated with type 1 diabetes mellitus (T1DM). Owing to the mitochondrial DNA heteroplasmy, there is a great variation in clinical presentation and severity of affected organ impairment among MDM patients. Furthermore, because of a poor response to oral hypoglycemic agents and increased lactate levels, MDM patients usually need insulin therapy, but not metformin. However, according to previous reports, not all MDM patients present with typical clinical features, especially at an early stage, and sometimes they are misdiagnosed as T1DM or T2DM and receive incorrect treatment. Currently, the correct diagnosis of MDM depends on DNA sequencing. However, because of the low prevalence of MDM and the complexity of genetic testing, it is not practical for every patient with diabetes to be sequenced. In this study, based on a review of all the reports of MDM in China, we established a scoring system for screening MDM patients (MDM‐score) based on multiple clinical indices and determined its effectiveness in identifying MDM patients from a hospitalized diabetes population.