title: Successful pregnancy outcomes in a patient with type A insulin resistance syndrome.
abstract: BACKGROUND
  The management of severe insulin resistance during pregnancy is challenging because of the increased risk of perinatal complications for both mother and fetus. We describe two consecutive pregnancies in a patient with severe insulin resistance caused by a mutation in the β subunit of the insulin receptor.
  
  
  METHODS
  A non-obese Japanese woman was diagnosed as having diabetes mellitus during her first pregnancy at age 31 years. She presented at 6 weeks' gestation with a fasting plasma glucose concentration of 15.1 mmol/l and an HbA(1c) level of 95 mmol/mol (10.8%). Fasting insulin concentration was high at 68.8 μU/ml, suggesting severe insulin resistance. Anti-insulin and insulin-receptor antibodies were both negative. Genetic analysis revealed an in-frame heterozygous deletion mutation (∆Leu(999)) in the insulin receptor gene. Despite large daily doses (up to 480 units per day) of insulin aspart and isophane, the patient's postprandial plasma glucose level exceeded 11.1 mmol/l. In the patient's second pregnancy, the addition of metformin at a dose of 2250 mg per day achieved tighter glycaemic control, with lower doses of insulin lispro and isophane (up to 174 units/day). Both newborns, who were found to carry the same mutation, were small for gestational age and developed transient hypoglycaemia after birth.
  
  
  CONCLUSIONS
  Adding metformin to the conventional insulin regimen effectively achieved tight glycaemic control with a lower dose of insulin. The mutation of the insulin receptor gene might underlie the intrauterine growth retardation of the newborns. To our knowledge, this is the first report of successful management of diabetes mellitus in a pregnant woman with type A insulin resistance syndrome.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Shimotsuke, Tochigi, Japan.
authors.forename: B
authors.initials: B
authors.lastname: Enkhtuvshin
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Shimotsuke, Tochigi, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Nagashima
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Shimotsuke, Tochigi, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Saito
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Shimotsuke, Tochigi, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Wakabayashi
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Shimotsuke, Tochigi, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Ando
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Shimotsuke, Tochigi, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Shimotsuke, Tochigi, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Sakai
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Shimotsuke, Tochigi, Japan.
authors.forename: D
authors.initials: D
authors.lastname: Yamamuro
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Shimotsuke, Tochigi, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Nagasaka
authors.affiliation: Division of Medical Biochemistry, Department of Biochemistry, School of Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Tamemoto
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Shimotsuke, Tochigi, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Ishibashi
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000235:genetics*; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007333:Insulin Resistance / Q000235:genetics*; D008687:Metformin / Q000627:therapeutic use; D009154:Mutation; D010375:Pedigree; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D011256:Pregnancy Outcome; D011972:Receptor, Insulin / Q000235:genetics*; D013577:Syndrome
chemical_list: D015703:Antigens, CD; D007004:Hypoglycemic Agents; D008687:Metformin; C435941:INSR protein, human; D011972:Receptor, Insulin