Unrecognized mitochondrial diabetes cases in a group of patients with type 2 diabetes

Maternally Inherited Diabetes and Deafness (MIDD) is a unique form of diabetes caused by β-cell dysfunction. Due to the highly variable symptoms of MIDD, it can be misdiagnosed as either type 1 or type 2 diabetes (T2D). The aim of this study was to identify pathogenic mtDNA variants (m.3243 A > G, m.8344 A > G, m.3271T > C, and m.12278T > C) in patients with initially diagnosed T2D.

A total of 102 patients diagnosed with T2D with their mean age of 64 ± 12.5 years, and BMI (body mass index) of 29.1 ± 5.8 kg/m² were recruited. DNA was isolated from the urine sediment and analyzed using real-time PCR with TaqMan probes. Next, positive results were confirmed by next-generation sequencing (NGS).

The m.3243 A > G variant was detected in 3/102 patients, accounting for 2.94% of the cohort. Patients with MIDD had a lower BMI (median 19.3 vs. 29.1 kg/m²) and an earlier age at diabetes onset (median 26 vs. 50 years) than the non-carrier group. In addition, all MIDD patients exhibited hearing impairment and a positive maternal history of hyperglycemia/diabetes and hearing loss.

Urine sediment testing appears to be an effective and non-invasive method for identifying previously undiagnosed cases of MIDD in patients with type 2 diabetes. Key diagnostic indicators include early onset of diabetes (average age of onset around 27), low BMI, and accompanying hearing loss. These factors are combined with a maternal history of other symptoms, such as hyperglycemia/diabetes and hearing impairment.