Endocrine Abstracts

Introduction: Primary mitochondrial disease is a heterogeneous group of disorders of mitochondrial energy metabolism. Neuromuscular symptoms are the main features, but diabetes mellitus (DM) is present in many patients. DM is related to a deficient energy production, which leads to decreased insulin secretion and ultimately to β-cell apoptosis. In most cases, DM has an insidious onset with requirement of insulin 2-4 years after diagnosis. About 20% of cases present with acute symptoms. We present two cases of patients with mitochondrial disorders, who developed DM.

Case 1: 36-year-old male, with mitochondrial encephalomyopathy, lactic acidosis, and stroke like episodes syndrome (MELAS) diagnosed at the age of 29, carrier of mtDNA mutation A3243G, with grade 4 tetraparesis, bilateral ptosis, cognitive impairment and epilepsy. He was under carbamazepine, valproic acid, idebenone, mirtazapine, riboflavin and a multivitamin supplement. He was admitted at the emergency department with symptoms of polyuria, polydipsia, dizziness and prostration. Blood tests revealed hyperosmolar hyperglycaemic syndrome, with venous glycaemia 989 mg/dL, plasma osmolality 325 mOsm/Kg, sodium 153 mmol/L, creatinine 1.1 mg/dL, normal pH and negative ketones. He started intravenous insulin and was admitted to the ward. He weighed 40Kg, with BMI 14.8Kg/m². Complementary investigation showed A1C 14.9%, C-peptide 0.1 ng/mL (1.0–7.6) and negative islet autoantibodies. He had improvement of clinical status and was discharged home with intensive insulin therapy, with total daily dose of 32U.

Case 2: 52-year-old female, with mitochondrial myopathy with Kearns-Sayre phenotype, with grade 4 tetraparesis, bilateral ptosis, external ophthalmoplegia, atrioventricular block (with pacemaker) and chronic respiratory failure. She had past history of papillary thyroid carcinoma (total thyroidectomy at the age of 46), DM diagnosed at the age of 48, hypertension, dyslipidaemia and depression. She was under metformin plus sitagliptin, levothyroxine, telmisartan plus hydrochlorothiazide, bisoprolol, omeprazole, fenofibrate, fluoxetine and valproic acid. She was admitted at Endocrinology department due to uncontrolled diabetes, to start insulin. She weighed 51Kg, with BMI 21.8Kg/m². Complementary investigation revealed A1C 10.7%, C-peptide 1.4ng/mL (1.0–7.6) and negative islet autoantibodies. Metformin was suspended due to hyperlactacidaemia and insulin glargine was started. She was discharged home with glargine 18U and sitagliptin 100 mg.

Conclusion: These cases show the heterogeneity of DM in mitochondrial disorders. Differential diagnosis with other forms of DM is challenging, because mitochondrial disorders are rare and present with very different phenotypes. DM treatment at initial stages, before insulin deficiency, is controversial.