Unveiling the spectrum of mitochondrial diabetes - a single center, multidisciplinary case series analysis

Sherf Rutie Mamlok; Efrat Markus; Miriam Shtainsneider; Peretz Shlomi; Shlomit Koren

doi:10.1530/endoabs.110.P368

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Endocrine Abstracts (2025) 110 P368 | DOI: 10.1530/endoabs.110.P368

ECEESPE2025 Poster Presentations Diabetes and Insulin (143 abstracts)

Unveiling the spectrum of mitochondrial diabetes – a single center, multidisciplinary case series analysis

Rutie Mamlok Sherf¹, Efrat Markus¹, Miriam Shtainsneider^{1, 2}, Peretz Shlomi³ & Shlomit Koren^{1, 2}

Author affiliations

¹Shamir Medical Center, Endocrine and Diabetes Institute, Zerifin, Israel; ²Tel-Aviv University, Faculty of Medicine, Tel Aviv, Israel; ³Shamir Medical Center, Neurologic ward, Zerifin, Israel

JOINT2224

Introduction: Mitochondrial diabetes is a rare form of adult-onset diabetes mellitus (DM) caused by mutations in mitochondrial DNA, most commonly in the MT-TL1 (m. 3243ANG) genotype. It manifests clinically as Maternally Inherited Diabetes and Deafness (MIDD) or Mitochondrial Encephalopathy with Lactic Acidosis and Stroke-like episodes (MELAS). The primary abnormality causing DM is inefficient and suboptimal glucose-stimulated insulin secretion. Treatment strategies for mitochondrial diabetes remain unclear due to sparse published evidence. Metformin therapy is generally avoided due to the high risk of lactic acidosis in this population.

Aim: To better define and understand the natural history of mitochondrial diabetes.

Results: A case series analysis was conducted on 14 patients treated at a multidisciplinary MELAS clinic over the past two years. Among them, 7 patients exhibited glucose homeostasis abnormalities: 6 were diagnosed with DM and 1 with Impaired Fasting Glucose. The mean age at DM diagnosis was 36. 1 years, while MELAS was diagnosed at 44. 3 years. Two patients were primarily diagnosed as type 1 DM despite negative anti GAD antibodies, and four patients were classified as type 2 DM on presentation. Treatment regimens included Insulin therapy (via Insulin pump or injections), GLP-1 agonists, SGLT2 inhibitors, Sulfonylurea and lifestyle modifications. Two patients had a history of lactic acidosis secondary to Metformin use, and one patient reported a history of Diabetic Ketoacidosis. The mean HBA1C level is 7. 04%. Microvascular complication were observed in three patients and included nephropathy and neuropathy, while none developed macrovascular complications. Additional comorbidities included overweight, dyslipidemia and hypertension in 3/7 patients. Other MELAS manifestations were hearing loss, stroke like events and cardiac complications in 6/7, 1/7 and 3/7 patients respectively. When compared to the 7 MELAS patients with normal glucose homeostasis, the patients with DM tended to be older (47 vs 35 years), had higher BMI (23. 8 vs 17. 9) and more comorbidities.

Conclusion: Mitochondrial diabetes is underrecognized, often diagnosed before MELAS, leading to potential mismanagement and complications. A multidisciplinary approach is essential to improve diagnosis, treatment, and patient outcome. Our specialized MELAS clinic provides valuable insights into the natural history and therapeutic strategies for this rare condition.