337-OR: Intensive Insulin Treatment in a Patient with Type A Insulin Resistance Syndrome Associated with a Novel Heterozygous Mutation of Trp1120Gly in the Insulin Receptor Gene

Abstract

Background: Type A insulin resistance syndrome is a rare congenital severe insulin resistance syndrome resulting from mutations in the insulin receptor (IR) gene. We herein report a case treated with continuous subcutaneous insulin infusion (CSII) followed by insulin glargine and pioglitazone. Clinical Case: A 16 year-old girl with BMI of 19.1 kg/m2, complained of primary amenorrhea and elevated glucose for 2 years. She was diagnosed with precocious puberty at the age of 7, and treated with letrozole and triptorelin successively for 6.5 years. Hyperinsulinemia was noted but not ameliorated with metformin treatment. All the treatment was suspended for 2 years before referring to our department. Plasma glucose during OGTT showed fasting glucose was 8.4 mmol/L, and 2-hour post-load was 23.5 mmol/L. HbA1c was 10.8%. Markedly increased fasting (245μU/mL) and post-load serum insulin (628μU/mL) were observed. Next generation sequencing revealed a novel heterozygous missense mutation of Trp1120Gly in the IR gene. The patient received CSII with 0.8U/kg as the starting daily total, and titrated the dosage according to SMBG, followed by insulin glargine and pioglitazone treatment. Her glucose was well controlled, insulin glargine was down to 8U/d at the end of 3 months. Her HbA1c dropped to 7.9%, along with fasting plasma glucose (4.6mmol/L) and serum insulin (95.44μU/mL), while 2-hour postprandial glucose and insulin were still high. Her menarche occurred after one cycle of ethinylestradiol and cyproterone combo tablets. Conclusion: Improvement of glucose control with intensive insulin treatment was observed in a patient with type A insulin resistance syndrome. However, amelioration of insulin resistance was limited. No standard treatment was recommended for this rare syndrome. Thus, large-scale long-term studies assembled worldwide to optimize treatment strategy are needed. Disclosure Y. Yang: None. Z. Huang: None. G. Wei: None. Y. Li: None. W. Deng: None. Y. Li: None. Funding National Natural Science Foundation of China (82070918)