The older of a pair of sisters experienced hypoglycemia after the start of thiamazole (MMI) treatment. Based on a high insulin antibody level, she was diagnosed with insulin autoimmune syndrome (IAS). HLA-DNA typing identified DRB1*04:06. Although a 75-g oral glucose tolerance test (OGTT) showed biphasic insulin secretion, the secretion pattern became monophasic after discontinuation of the MMI. The younger sister was diagnosed with IAS after the start of MMI treatment. HLA-DNA typing identified DRB1*04:06. The 75-g OGTT showed biphasic insulin secretion, but it became monophasic after discontinuation of the MMI. According to the similar insulin secretion kinetics in the two sisters with IAS, we suspect that a genetic predisposition may be associated with the features of anti-insulin antibodies.