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

## TL;DR

This study examines how insulin treatment affects IGF-I bioavailability in children with type 1 diabetes by analyzing changes in PAPP-As and STCs over time.

## Contribution

The study reports for the first time serum concentrations of PAPP-As and STCs in children with T1DM and their changes during insulin treatment.

## Key findings

- Insulin treatment increased STC2 and decreased PAPP-A2 concentrations in children with T1DM.
- HbA1c correlated positively with PAPP-A2 and negatively with STC2.
- Metabolic control improved over 12 months of treatment, but changes in IGF bioavailability did not significantly affect free IGF-I levels.

## Abstract

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.

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 axis, beta-cell insulin reserve, auxology, and nutritional status.

A single-center prospective observational study including 47 patients (59.5% male), with T1DM onset at median age of 9.2 years (interquartile range: 6.3, 11.9) was performed. Blood and anthropometric data were collected at diagnosis and after 6 and 12 months of treatment.

At 6 and 12 months after T1DM diagnosis, there was improvement in the metabolic control (decrease in glycated hemoglobin [HbA1c] at 12 months −3.66 [95% CI: −4.81, −2.05], P = .001), as well as in body mass index SD and height SD (not statistically significant). STC2 increased (P < .001) and PAPP-A2 decreased (P < .001) at 6 and 12 months of treatment onset (P < .001), which was concurrent with increased total IGF-I and IGF-binding protein concentrations, with no significant modification in free IGF-I concentrations. HbA1c correlated with PAPP-A2 (r = +0.41; P < .05) and STC2 (r = −0.32; P < .05).

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.