Endocrine Abstracts

Case history: A 41-year-old lady referred to diabetes clinic due to chronic diarrhoea on Metformin and for consideration of any injectable treatment. HbA1c was 41 and BMI is 35. In 2007, OGTT during pregnancy showed fasting glucose of 4.1 mmol/l and 2 h glucose of 7.8 mmol/l. In 2013 her fasting glucose was 7.5 and HbA1c was elevated at 53 mmol/mol. Since July 2013 she has been diagnosed as type 2 DM and started on Metformin. In October 2013 HbA1c fell to 49. Over the succeeding years her HbA1c has never been greater than 41 mmol/l. She has a very strong family history of diabetes. Mother was diagnosed with diabetes in her early 30s and she had deafness. Her brother has been diagnosed with type 1 diabetes and he has deafness in both ears. Maternal grandmother and her brothers were also diagnosed with type 1 diabetes. Our patient is also suffering from deafness in her left ear.

Investigations: Diagnosis of maternally inherited diabetes and deafness (MIDD) is considered in our patient. Diabetes related antibodies (Anti GAD Antibodies, IA2 Antibodies and Znt8 Antibodies) were requested. A genetic test is requested for possible diagnosis of MIDD.

Results and treatment: All diabetes related antibodies came back negative. The pathogenic mitochondrial DNA (mtDNA) variant NC_012920.1:m.3243A>G was detected in patient’s urinary epithelial cell DNA sample (Royal Devon and Exeter NHS Foundation Trust, UK). The m.3243A>G mitochondrial variant is associated with MIDD (maternally inherited diabetes and deafness) and MELAS (mitochondrial encephalopathy, lactic acidosis and stroke-like episodes). The patient is correctly diagnosed with MIDD. Given her HbA1c of 41, diarrhoea and diagnosis of MIDD, metformin was stopped. She is appropriately screened for other associated conditions.

Discussion: •  To identify patients with MIDD is challenging but important as therapy is different from individuals with type1 and type 2 DM. Our patient and her brother were wrongly diagnosed as type 2 DM and type 1 DM respectively in this case. A very strong family history of DM and deafness should prompt an investigation for MIDD.

•  It should be noted that Metformin, the most commonly used first-line mediation for type 2 DM, may actually be harmful because of the increased risk of lactic acidosis in these individuals.

•  There are many reported clinical manifestations of m.3243A>G mutation. Individuals who are correctly diagnosed will be screened for those manifestations.

•  Genetic testing can be offered to maternal relatives and offspring.