Endocrine Abstracts

Background: Maternally inherited diabetes and deafness (MIDD) is a rare disease affecting approximately 1% of all diabetics. The most common mutation involved is a single base mutation (A-G) at position 3243 within the tRNA^LEU(UUR) gene. The clinical characteristics normally associated with this disease include sensorineural hearing loss, macular pattern dystrophy, cardiomyopathy, and diabetes. This study aims to identify clinical phenotype and insulin secretory response to glucose.

Methods: We prospectively studied 33 patients from 23 different pedigrees with MIDD, all of which were identified from the Mater-MODY cohort database. Audiograms, ECHO’s and biochemical markers including Hba1c, Lactate, Creatinine Kinase (CK) were performed. 2-hr OGTT’s were performed to determine the degree of glucose tolerance, C-peptide and insulin secretory response. Clinical and metabolic data outcomes were analysed.

Results: 23 (72%) patients have diabetes with 1 pre-diabetic and 9 non-diabetics. The mean age was 49.7(±12.8)y/o and BMI is 23.5(±3.2)kg/m². 6 (18.2%)patients were misidentified as Type 1 Diabetics while 14 (42.4%) as type 2 Diabetics. 31 patients (93.9%) had the mtDNA 3243A>G mutation. 1 had Kearns-Sayre syndrome. 1 had the m.12258C>A mutation. Heteroplasmy was determined in 24 patients (69.7%) using blood leucocytes with ranges of 3–41%. 28 patients (84.8%) were found to have sensorineural hearing loss. 8 patients (24.2%) developed cardiomyopathy. Only 1 (3.0%) patient had maculopathy and 5 patients (16.1%) developed MELAS. 8 (24.2%) patients had ophthalmopathy. 14 (42.4%) patients had 2-hr OGTT’s which showed glucose (mmol/L), insulin (pmol/L) and C peptide (pmol/L) mean level at baseline/120 mins as follows: 7.8 (±4.3)/13.3 (±7.7), 63.3 (±25.8)/297.3 (±170.8), and 570.6 (±201.4)/2318.7 (±1224.8). 31 (93.9%) patients had HBa1c with mean of 66.4 (±18.6) mmol/mol. 13(39%) patients had metformin discontinued. 14(42.4%) patients are on insulin alone. 5(35.7%) are on insulin and OHA’s. 4 (12.1%) are on sulphonylurea alone.

Conclusion: There is a wide phenotypic variability seen in MIDD which can lead to misdiagnosis and induction of inappropriate therapy. Patients with diabetes and deafness should arouse suspicion of mitochondrial diabetes as well as those who are young and lean diabetics with rapid progression to insulin. These patients also have a good insulin secretory response seen on OGTT. However, 54% of patients have ended up on insulin with mean HBa1c of 66.4 mmol/mol indicating diabetic control remains brittle.