Implication of Pappalysins and Stanniocalcins in the Bioavailability of IGF-I in Children With Type 1 Diabetes Mellitus

Abstract

Introduction Anomalies in the growth hormone (GH) - insulin-like growth factor (IGF) axis, are common in children with type 1 diabetes mellitus (T1DM), even in those reaching a normal or near-normal final height. However, concentrations of the IGF bioavailability regulatory factors [pappalysins (PAPP-As) and stanniocalcins (STCs)] have not been reported in children with T1DM. Aims To determine serum concentrations of PAPP-As and STCs in children at diagnosis of T1DM and after insulin treatment and the correlation of these factors with other members of the GH/IGF, beta-cell insulin reserve, auxology and nutritional status. Methods A single-center prospective observational study including 47 patients (59.5% males), with T1DM onset at median age of 9.2 (IQR: 6.3, 11.9) years was performed. Blood and anthropometric data were collected at diagnosis and after 6 and 12 months of treatment. Results At 6 and 12 months after T1DM diagnosis, there was improvement in the metabolic control [decrease in HbA1c at 12 months -3.66 CI95% (-4.81, -2.05), p=0.001], as well as in body mass index SD and height SD (not statistically significant). STC2 increased (p<0.001) and PAPP-A2 decreased (p<0.001) at 6 and 12 months of treatment onset (p<0.001), which was concurrent with increased total IGF-I as well and IGFBP concentrations, with no significant modification in free IGF-I concentrations. HbA1c correlated with PAPPA-2 (r: +0.41; P<0.05) and STC2 (r: -0.32; P<0.05). Conclusions Implementation of insulin treatment after T1DM onset modifies various components of the circulating IGF system, including PAPP-A2 and STC2. How these modifications modulate linear growth remains unknown.