biostudies-literatureUnknown12(3)Gude MF<h4>Objective</h4>Physiologically, pregnancy-associated plasma protein-A (PAPP-A) serves to liberate bound IGF1 by enzymatic cleavage of IGF-binding proteins (IGFBPs), IGFBP4 in particular. Clinically, PAPP-A has been linked to cardiovascular disease (CVD). Stanniocalcin-2 (STC2) is a natural inhibitor of PAPP-A enzymatic activity, but its association with CVD is unsettled. Therefore, we examined associations between the STC2-PAPP-A-IGFBP4-IGF1 axis and all-cause mortality and CVD in patients with type 2 diabetes (T2D).<h4>Design</h4>We followed 1284 participants with T2D from the ADDITION trial for 5 years.<h4>Methods</h4>Circulating concentrations of STC2, PAPP-A, total and intact IGFBP4 and IGF1 and -2 were measured at inclusion. End-points were all-cause mortality and a composite CVD eEndocrine connectionse220451https://www.ebi.ac.uk/biostudies/studies/S-EPMC9986395biostudies-literatureThe STC2-PAPP-A-IGFBP4-IGF1 axis and its associations to mortality and CVD in T2D.PMC9986395Bjerre MHjortebjerg RSandbæk ACharles MHGude MFWitte DRFrystyk JfalseThe STC2-PAPP-A-IGFBP4-IGF1 axis and its associations to mortality and CVD in T2D.<h4>Objective</h4>Physiologically, pregnancy-associated plasma protein-A (PAPP-A) serves to liberate bound IGF1 by enzymatic cleavage of IGF-binding proteins (IGFBPs), IGFBP4 in particular. Clinically, PAPP-A has been linked to cardiovascular disease (CVD). Stanniocalcin-2 (STC2) is a natural inhibitor of PAPP-A enzymatic activity, but its association with CVD is unsettled. Therefore, we examined associations between the STC2-PAPP-A-IGFBP4-IGF1 axis and all-cause mortality and CVD in patients with type 2 diabetes (T2D).<h4>Design</h4>We followed 1284 participants with T2D from the ADDITION trial for 5 years.<h4>Methods</h4>Circulating concentrations of STC2, PAPP-A, total and intact IGFBP4 and IGF1 and -2 were measured at inclusion. End-points were all-cause mortality and a composite CVD e2023-01-01T00:00:00Z2023 Mar2025-04-21T19:51:13.189Z2025-02-18T23:26:15.906ZS-EPMC99863953660715410.1530/EC-22-0451