Gestational diabetes mellitus (GDM), defined by the occurrence or discovery of glucose intolerance during pregnancy is associated with higher risk of perinatal complications and long-term development of chronic diseases both in the mother and her child. Recent data suggest that women diagnosed earlier in pregnancy, even having more risk factors, develop fewer complications. The aim of the current study is to analyse biochemical markers that play a role in the pathophysiology of GDM and could lead to an early diagnosis. The authors performed a case-control study on 50 pregnant women that finally developed GDM and 50 pregnant women with risk factors for GDM which did non develop the disease. In all cases there were monitored a series of biochemical markers like glycated haemoglobin (HbA1c), sex hormone binding globulin (SHBG), magnesium (Mg), C-reactive protein (CRP), plasma insulin level, and pregnancy-associated plasma protein A (PAPP-A). All these factors were statistically analysed using univariate and multivariate tests in order to evaluate their predicting value. The combination of traditional risk factors with HBA1c, SHBG, PAPP-A and CRP proved significant prognosis value (75% sensitivity rate, 9% false positive rate) for GDM. In conclusion, these four biochemical markers available in early pregnancy have improved the performance of predicting models concerning the development of severe GDM needing insulin treatment and predisposing to maternal and foetal complications.