Introduction
Gestational diabetes (GD) is a common metabolic disorder of pregnancy characterized by insulin resistance and altered glucose-lipid metabolism.1 The offspring of GD mothers are at elevated risk of obesity and impaired glucose tolerance during adolescence, and increased risk of diabetes in later life.2 3 How this increased susceptibility to metabolic dysfunctional disorders is developed in early life remains unclear. Impaired insulin sensitivity has been observed in the newborns of mothers with GD,4 and in large for gestational age (often a suspected consequence of varying degrees of hyperglycemia in pregnancy) newborns,5 Plausibly, altered levels of insulin sensitivity regulation adipokines may be involved.
Leptin and adiponectin are important adipokines in regulating insulin sensitivity.6 Adiponectin exists in low, medium and high molecular weight (HMW) forms, and HMW adiponectin is recognized as the most bioactive form of adiponectin as related to its insulin-sensitizing property.6 Studies have reported elevated cord blood leptin and decreased adiponectin levels in GD,7–9 but no significant differences have also been observed in some studies.10 Retinol-binding protein 4 (RBP-4) is an adipokine implicated in insulin resistance.11 Circulating RBP-4 concentration was positively correlated with insulin resistance in subjects with obesity and type 2 diabetes.12 There have been inconsistent data concerning whether there are significant changes in maternal circulating RBP-4 levels in GD.13–17 We are aware of only one study on cord blood RBP-4 levels in GD pregnancies.9
Studies have demonstrated that females are more insulin resistant than males in utero,18 19 and more likely to develop diabetes at young ages.20 21 It is unclear whether the early life origins of such elevated vulnerability in females may be related to any alterations in insulin sensitivity regulating adipokines such as leptin, adiponectin and RBP-4. Sex dimorphisms in cord blood leptin and adiponectin concentrations have been reported, possibly attributable to the effects of body fat.7 22 It is unknown whether GD may affect any sex dimorphism in fetal (cord) blood levels of leptin, adiponectin and RBP-4.
In view of the above-described knowledge gaps, the present study sought to determine whether there are alterations in cord blood leptin, adiponectin and RBP-4 levels in GD, and assess whether there is sex dimorphism in the associations of GD with cord blood RBP-4, leptin and adiponectin levels in a large birth cohort.