1136-P: Type A Insulin Resistance Masquerading as Type 1 Diabetes Mellitus

Abstract

More than 150 mutations in the INSR gene encoding the insulin receptor have been identified causing a spectrum of insulin resistance syndromes from mild (type A insulin resistance) to more severe (Rabson-Mendenhall syndrome, Donahue syndrome). Type A insulin resistance typically presents in childhood or early adulthood. We describe a 19-year-old male with type A insulin resistance due to heterozygous INSR gene mutation, c.3470A>G (His1157Arg). This mutation has previously been identified in female patients with hyperglycemia, insulin resistance. The patient presented at age 14 with polyuria, polydipsia, hyperglycemia (glucose 200s) without acidosis, and normal BMI (50th%) and was presumed to have type 1 diabetes. He was treated with insulin though required escalating doses to 2-2.5 units/kg/day and was started on metformin to improve insulin sensitivity which had a minor effect on total daily insulin requirements. HbA1c was typically 7-9% for several years with this treatment plan and BMI remained near 50th%. The patient was subsequently lost to follow-up and after self-discontinuing insulin for approximately 1 year, re-presented with hyperglycemia, the absence of ketonuria or acidosis, elevated insulin level (92.2 μIU/ml), negative islet cell antibodies, HbA1c 10.9%. Notably, he did not have acanthosis nigricans. Subsequent genetic testing revealed a mutation in the INSR gene consistent with type A insulin resistance. This case highlights the importance of considering monogenic forms of diabetes and insulin resistance syndromes in lean patients who require higher-than-expected insulin doses with presumed type 1 diabetes. Disclosure E.A.Los: Other Relationship; Medtronic. K.Wirthwein: None.