Introduction
Recent estimates indicate that 32% of women in reproductive age (20–39 years) are obese.1 The prevalence of obesity in pregnancy has become a significant obstetrical challenge due to the increased risk of pregnancy complications in these women including gestational hypertension, pre-eclampsia, and gestational diabetes mellitus (GDM) as well as operative and postoperative complications following cesarean delivery.2 The fetus can also be negatively affected by high maternal adiposity with increased risk for stillbirth, prematurity, shoulder dystocia, and fetal overgrowth.3
Obese pregnant women often enter pregnancy with mild insulin resistance, which is associated with hyperinsulinemia. The incidence of GDM in obese mothers is nearly double compared with mothers of normal body mass index (BMI, kg/m2).4 Advances in detection and treatment of GDM in recent years have not alleviated the unfavorable intrauterine environment for the developing fetus, and fetal overgrowth continues to be a major problem in these pregnancies.5 ,6 Large-for-gestational-age children have a higher long-term risk for metabolic and cardiovascular disease.7 Pregnancy complicated by GDM also increases the risk for the mother as well as the fetus to develop metabolic and cardiovascular diseases later in life.8
Mexican-American women of reproductive age (20–39) have a greater prevalence of overweight and obesity (69%) than non-Hispanic White women (51%).1 The frequency of GDM has been reported to be 13% in obese Hispanic women compared with 7% for obese Caucasian women.4 ,9 Therefore, babies of Hispanic women are at particular risk of exposure to the adverse intrauterine metabolic environment associated with maternal obesity and GDM, which may predispose them for obesity and diabetes. This may contribute to the very high rate of childhood and adolescent obesity (21% with BMI >95th centile) in Hispanic children and adolescents.10
Insulin resistance has been identified as a common underlying factor for poor pregnancy outcomes.11 The ability to diagnose abnormal insulin resistance in pregnancy is complicated by the natural decrease in insulin responsiveness that occurs in all pregnant women. Adiponectin has well-established insulin sensitizing properties and circulating levels of adiponectin decrease with increasing BMI, contributing to insulin resistance in obese non-pregnant participants. In pregnancy, low maternal adiponectin levels have been reported in women diagnosed with GDM.12–23 However, maternal BMI was not consistently accounted for in these reports.
Adiponectin is found in multimeric forms in the circulation commonly known as high-molecular-weight (HMW), middle-molecular-weight, and low-molecular-weight forms. Most metabolic effects of adiponectin can be attributed to HMW forms24 and the strongest predictor of insulin sensitivity in non-pregnant individuals is the HMW adiponectin/total adiponectin ratio. In pregnancy, the relationship between HMW adiponectin and insulin sensitivity appears to be similar with HMW adiponectin being positively correlated with insulin sensitivity and HMW forms reported to be reduced in GDM mothers.18 ,25 Naruse et al26 observed a decline in HMW adiponectin as gestation progresses. In contrast, Mazaki-Tovi et al17 reported no change with gestation in any multimeric form. Low maternal levels of HMW adiponectin have been reported in GDM pregnancies12–23 as well as in pregnancies complicated by small-for-gestational-age fetuses.27 Maternal HMW adiponectin is increased in pre-eclampsia.28 Interestingly, cord serum HMW adiponectin levels are higher than in maternal serum and are positively correlated to birth weight29–31 in most but not all32 studies.
Maternal circulating levels of insulin-like growth factor I (IGF-I) and its binding proteins (IGFBP) increase over gestation. This is likely due to the effects of placental growth hormone on hepatic IGF-I release.33 Maternal IGF-I correlates positively with birth weight and placental weight, and maternal IGF-I is significantly higher in GDM pregnancies compared with non-diabetic pregnancies.34 ,35 Maternal IGF-I levels are positively correlated with pre-pregnancy BMI, fasting insulin, and the homeostasis model assessment of insulin resistance (HOMA-IR) in individuals with gestational diabetes but not in control pregnancies suggesting that elevated IGF-I may contribute to insulin resistance in women with GDM.34 One study suggested that early pregnancy IGF-I plasma levels may be predictive of GDM.36 The predominant IGFBP-isoform 3 is degraded in pregnancy resulting in increased IGF-I availability.37 This data suggests that IGFBP-1 plays an important role in modulating IGF-I bioavailability during pregnancy. IGFBP-1 is negatively correlated with birth size in normal and diabetic pregnancies.38 ,39
Our study was designed to examine maternal metabolic parameters (glucose and lipids), hormones (insulin, IGF-I, IGFBP-1), and adipokine levels (adiponectin, leptin, interleukin (IL)-6, and tumor necrosis factor (TNF) α) in obese pregnant women. This study was conducted at 24–28 weeks of gestation in predominantly Hispanic women with pre-pregnancy BMI >30 with or without recent diagnosis of GDM. We hypothesized that lower adiponectin, in particular the HMW form, and IGFBP-1 and higher IGF-I are associated with the diagnosis of GDM in pregnancies complicated by maternal obesity.