Endocrine Abstracts

A 25-year-old female was referred to the diabetes service for specialist management of her type 2 diabetes. She was diagnosed with diabetes mellitus at 7 years and attended paediatric services. At diagnosis she was non-ketotic and did not behave as autoimmune mediated diabetes. She was treated as type 2 diabetes mellitus with diet and metformin. Throughout her childhood she was serially evaluated for alternative causes of this atypical diabetes presentation. Islet antigen autoantibodies were negative and so too was genetic testing for GCK and HNF1A mutations. During adolescence a hyperandrogenic phenotype emerged in keeping with polycystic ovarian syndrome, and she was considered to have an insulin resistance phenotype. On assuming care of this patient her assessment revealed acanthosis nigricans, hirsuitism and pseudoacromegalic features. There was no lipodystrophy. Triglyceride levels were normal indicating that the insulin resistance was arising at the level of the insulin receptor. There was an autosomal dominant pattern of diabetes in her family, however she was the only female in the pedigree impacted. Insulin levels confirmed hyperinsulinaemia at 4,991 pmol/l (18-173 pmol/l). A clinical diagnosis of type A insulin resistance was made, and genetic testing confirmed a heterozygous pathogenic missense variant in the insulin receptor gene (INSR). Type A insulin resistance is a rare inherited cause of diabetes. Recognition is essential to facilitate genetic counselling, family screening, and access to specialist care, while allowing consideration of emerging targeted therapies. Affected females experience additional challenges with hyperandrogenism and infertility. Tailored management involves prioritising insulin-sensitisation with pharmacotherapy and lifestyle modification.