Comprehensive Phenotype and Treatment Description of Mitochondrial Diabetes: Insights from a Large Cohort Study.

OBJECTIVE Mitochondrial diabetes (mtDB) is a rare form of diabetes with limited information regarding its clinical spectrum, and long-term outcomes. This study aimed to describe the glycemic control, treatment patterns, and associated comorbidities among patients with mtDB.

METHODS We identified 30 patients with diabetes and confirmed mitochondrial mutations, predominantly the MT-TL1 m.3243A>G variant (n=28). Monogenic diabetes genes, including MODY-associated variants, were not evaluated. Statistical analyses were performed using BlueSky Statistics (v10.3.4). Categorical variables were assessed using Fisher's exact and ANOVA tests, and continuous variables using univariate analysis.

RESULTS The cohort was 63.3% female, with a mean age at diabetes diagnosis of 38.0 (±13.0) years for females and 34.6 (±13.7) years for males. More than 70% were initially misdiagnosed with type 2 diabetes (T2D), resulting in an average diagnosis delay of 9.3 years from the date of their diabetes diagnosis. Mean BMI at diagnosis was 25 kg/m2 (±11.3). The cohort demonstrated a high burden of comorbidities-including retinopathy, neurological disease, cardiac arrhythmias, nephropathy, and gastrointestinal disorders-many of which preceded diabetes onset. Glycemic control remained stable, with more than 90% maintaining HbA1c <8%. Treatment modality (insulin vs. non-insulin) did not significantly impact HbA1c levels (mean 6.85%) though the study's descriptive design and small sample size may limit interpretability. Mean survival after mtDB diagnosis was 8 years (±10.3), and four patients died from mitochondrial disorder-related complications.

CONCLUSION mtDB is frequently misdiagnosed as T2D and is associated with multisystem comorbidities. Earlier recognition and individualized management strategies are essential to improve outcomes.