Abstract. By biochemical and epidemiological similarity with type 2 diabetes mellitus (T2DM), gestational diabetes mellitus (GDM) has some overlap between prediction markers and risk factors of T2DM. The present study aimed to establish that secreted frizzled-related protein 4 (SFRP4) and ficolin-3 levels, which have been linked to insulin resistance and the development of T2DM, are elevated in GDM women. A longitudinal prospective cohort study of 86 GDM and 273 normal glucose tolerant (NGT) pregnant women was performed. The clinical parameters, lipid profiles, and serum SFRP4 and ficolin-3 levels were tested during the early and late second-trimester and third-trimester of pregnancy. Both SFRP4 and ficolin-3 levels were significantly higher in GDM women as compared to the NGT participants at three test points (p < 0.01). Spearman's correlation analysis showed that serum SFRP4 levels were significantly positively correlated with ficolin-3 during the early and late second-trimester and third-trimester of pregnancy. The elevated SFRP4 and ficolin-3 concentrations at 16-18 weeks gestation significantly associated with GDM were conformed using binary logistic regression analysis after controlling for other variables [odds ratios (OR) with 95% confidence intervals (CI) for SFRP4: 2.84 (1.78-4.53), p < 0.01; for ficolin-3: 2.45 (1.55-3.88), p < 0.01]. In Conclusions, increased SFRP4 and ficolin-3 levels are significantly associated with GDM development and might be important risk factors for this pregnancy complication.Key words: Gestational diabetes mellitus, Secreted frizzled-related protein 4, Ficolin-3 doi:10.1507/endocrj.EJ17-0508 GDM, a state of varying degree of carbohydrate intolerance with onset or first recognition during pregnancy, may result in a rapid global increase in T2DM [1]. This epidemic is associated with a high risk of developing T2DM in both GDM mothers and their children. Due to biochemical and epidemiological similarity with T2DM, GDM shows cross-talk with predictive markers and risk factors of T2DM [2]. A correlation between cytokine levels (adipokines and inflammatory markers) and the risk of T2DM is also extended to GDM [3].SFRP4 has recently been associated with insulin reSubmitted Dec. 1, 2017; Accepted Jan. 17, 2018 as EJ17-0508 Released online in J-STAGE as advance publication Feb. 27, 2018Correspondence to: Bin Yu, Department of Prenatal Diagnosis Laboratory, Changzhou Maternity and Child Health Hospital Affiliated to Nanjing Medical University, 26th Bo Ai Road, Changzhou, Jiangsu 213003, China. E-mail: ybcz0519@163.com sistance and the development of T2DM [4]. SFRP4 is one of the Wnt signaling antagonists, which has been newly described to be involved in lipid and glucose metabolism through interaction with the Wnt ligands. The elevated SFRP4 is associated with obesity, type 1 diabetes mellitus (T1DM) and T2DM as demonstrated in previous studies [5][6][7][8][9]. However, the correlations between the changes of soluble SFRP4 and GDM are unclear. Ficolin-3 is a circulating pattern recogn...