Association of insulin receptor substrate-1 G972R variant with baseline characteristics of the patients with gestational diabetes mellitus Ekrem C. Tok, MD, a Devrim Ertunc, MD, a Ozlem Bilgin, MD, a Emin M. Erdal, MD, b Mustafa Kaplanoglu, MD, a Saffet Dilek, MD a Departments of Obstetrics and Gynecology a and Genetics, b Mersin University School of Medicine, Mersin, Turkey Received for publication July 5, 2005; revised August 17, 2005; accepted August 24, 2005 KEY WORDS Gestational diabetes mellitus Insulin receptor substrate-1 G972R polymorphism Objective: Insulin receptor substrate-1 (IRS-1) expression and tyrosine phosphorylation is decreased during pregnancy. Pregnancy may be a suitable condition to detect any abnormalities related to IRS-1 polymorphisms. Therefore, we aimed to investigate the prevalence and metabolic impacts of IRS-1 G972R polymorphism in patients with gestational diabetes mellitus (GDM). Study design: Anthropometric and metabolic variables of 62 women who were diagnosed as having GDM according to 100 g oral glucose tolerance test were compared on the basis of IRS-1 polymorphism by univariate analysis of covariance. Results: Patients with IRS-1 G972R were more obese at the beginning of pregnancy, had higher serum fasting insulin and glucose levels. Weight gain during pregnancy and insulin and glucose levels after glucose ingestion was comparable between groups. Conclusion: IRS-1 G972R was associated with the baseline characteristics of the patients with GDM, and might be related to insulin resistance that is seen in obese patients with GDM. Ó 2006 Mosby, Inc. All rights reserved. Normal human pregnancy is characterized with hy- perinsulinemia and a progressive decline in insulin sen- sitivity. Studies using hyperinsulinemic euglycemic clamp technique showed a 40% to 60% reduction in whole body glucose disposal from early to late pregnancy. 1 Although most pregnant women maintain normal glu- cose tolerance by a compensatory increase in insulin secretion, 3% to 5% of pregnancies are complicated with gestational diabetes mellitus (GDM). 2 Even though the precise mechanisms that lead to occurrence of GDM is unkown yet, defects involving glucose transport in muscle and adipose tissue are likely responsible. 3 Sus- ceptibility to GDM has been suggested to have genetic determinants. 4 Accordingly, considerable effort has been devoted to identify genes that contribute to this genetic predisposition, and several authors have screened for the presence of mutations in candidate genes encoding pro- teins involving in insulin actions 5 or insulin secretion. 6 Insulin initiates a wide variety of growth and meta- bolic effects by binding to the insulin receptor and activating its tyrosine kinase. This event leads to phopshorylation on tyrosine residues of a variety of docking proteins, including insulin receptor substrate (IRS) proteins. Phosphorylated IRS proteins, in turn, activate various molecules possessing src homology 2 Reprints not available from the authors. 0002-9378/$ - see front matter Ó 2006 Mosby, Inc. All rights reserved. doi:10.1016/j.ajog.2005.08.067 American Journal of Obstetrics and Gynecology (2006) 194, 868–72 www.ajog.org