[A case of familial insulin resistance due to type A insulin receptor disorder]

We report a case of familial insulin resistance due to Type A insulin receptor disorder. The patient, a product of consanguineous marriage, was a 34-year-old man who had had diabetes mellitus since the age of 14 years. He was treated by insulin therapy but became blind due to diabetic retinopathy at the age of 25 years. He was 154 cm tall and weighed 41kg. He had hirsutism and acanthosis nigricans. Laboratory data revealed hyperinsulinemia (140-350 microU/ml), and glucose clamp study showed insulin resistance, i.e. decreased glucose metabolic clearance rate, 20% of normal. Insulin binding was decreased to 10.7-16.6% of normal in erythrocytes, cultured fibroblasts and transformed lymphocytes. Glucagon stimulated C-peptide levels decreased gradually during a 3 year follow-up period. Homologous missense mutation from Proline193 to Leucine193 was found in this patient. Heterologous mutation was found in his mother who showed mild diabetes but did not show hirsutism or acanthosis nigricans. These findings suggested that the patient's father had this mutation in his insulin receptor gene and that the homologous mutation gene provoked more severe diabetes mellitus than heterologous mutation in this case. The efficacy of sulfonylurea agents was seen in this patient. Furthermore, sulfonyl urea agents may be indicated for treating these patients, probably by increasing insulin sensitivity.