Objectives: Evaluation of serum levels of visfatin, tumor necrosis factor-α (TNF-α), afamin, and fetuin-A in euglycemic
women at the time of pregnancy diagnosis (Booking time) as early discriminators for women vulnerable to develop gestational diabetes mellitus (GDM).  Patients and Methods: 150 euglycemic newly pregnant women were clinically evaluated and gave blood samples at booking time and at the 24th gestational week (GW). Glucose intolerance was diagnosed using the 75-gm oral glucose tolerance test (OGTT), glycemic control state was checked by the level of glycated hemoglobin (HbA1c), and insulin resistance (IR) was diagnosed using the homeostasis model assessment of IR (HOMA-IR) score. Serum levels of the studied biomarkers were estimated at-booking time and at the 24th GW. Group IR/GDM included women who developed IR and/or GDM, group IS/ NG included women who continued their pregnancy free of IR or GDM.  Results: At the 24-GW, all women had higher blood glucose (BG) and HbA1c levels, and HOMA-IR index in comparison to their booking levels, but the difference was significant for women of IR/GDM group and 22 women (14.7%) developed GDM, while 58 women (38.7%) developed IR. At the 24th GW, serum levels of the four biomarkers were significantly higher in blood samples of women of IR/GDM group in comparison to their at-booking levels and to corresponding levels of women of IS/NG group. Statistical analyses defined high at-booking serum TNF-α and afamin levels as early predictors for uncontrolled BG levels, while high TNF-α, visfatin, and afamin serum levels are the significant predictors for HOMA-IR of >2 at the 24th GW.  Conclusion: Elevated serum levels of the studied biomarkers early in pregnancy may play a role in the development of GDM. High serum TNF-α and afamin might be used as early discriminative biomarkers for women liable to develop GDM and/or IR later in pregnancy.