Screening for glucose intolerance during pregnancy provides an opportunity to offer management to those women diagnosed with gestational diabetes mellitus. However, there is a need to diagnose gestational diabetes early to minimize exposure of the developing fetus to suboptimal conditions and prevent perinatal complications and their sequelae. The purpose of this study was to identify potential biomarkers for impending gestational diabetes that appear in the plasma before impaired glucose tolerance. Pregnant women were prospectively recruited to the study and blood was collected at the first antenatal visit and at the time of routine oral glucose tolerance test. Women diagnosed with gestational diabetes were matched with an equal number of normal pregnant (control) women. Biomarkers under investigation included endocrine and metabolic hormones, cytokines and chemokines, and surrogate markers of oxidative stress. Compared to controls, women with gestational diabetes exhibited elevated plasma insulin and reduced plasma adiponectin concentrations at 28 weeks gestation. Significant differences in insulin and adiponectin concentrations were also observed in plasma at 11 weeks gestation. Bivariate logistic regression analysis showed that both insulin and adiponectin are associated with subsequent development of gestational diabetes. Plasma insulin and adiponectin concentrations, when measured at 11 weeks, may be predictive of impending gestational diabetes. Further studies are warranted to determine the reliability of these biomarkers.