Are pappalysins and stanniocalcins involved in modifying the bioavailability of IGF-I in children with onset of type 1 diabetes mellitus?

Maria Güemes; Sandra Canelles; Álvaro Martín-Rivada; Beatriz Corredor; Vicente Barrios; Jesús Argente

Introduction: Both poor and optimal metabolic control of type 1 diabetes mellitus (T1DM) in children can impact longitudinal growth. A decrease in insulin-like growth factor (IGF)-I and its binding protein 3 (IGFBP3) has been described in these patients. New growth regulatory factors [pappalysins (PAPP-As) and stanniocalcins (STCs)] could modulate the bioavailability of IGFs by regulating the concentrations of intact and free IGFBPs.

Aims: To study the effect of insulin treatment on serum concentrations of pappalysins and stanniocalcins and the possible correlation with markers of the growth axis, beta-cell insulin reserve, auxology and nutrition in children with T1DM.

Methods: 47 patients were included (59.5% females), with diabetes onset at age 9.08 +/- 5.8 years (median +/- interquartile range). Blood was extracted and anthropometric data collected at onset, 6 and 12 months. Serum concentrations were obtained using ELISAs, except PAPP-A2 (chemiluminescence immunoassay); all were standardized for age, sex, and pubertal development.

Results: Table 1 shows the results of the serum concentrations. At 6 and 12 months after T1DM onset, there was improvement in the metabolic control [decrease in HbA1c at 12 months -3.66 IC95%(-4.81,-2.05), P=0.001], certain nutritional markers [30.91 IC95%(0.36,61.47) P<0.05 for transferrin], body mass index SDS and height SDS (not statistically significant).


Analyte (SD)	Onset [median (IQR)]	6 months [median (IQR)]	12 months [median (IQR)]
Total IGF-I	-1.20 (-1.56,-0.50)	-0.04 (-0.77,0.3)***	-0.53 (-0.89,0.25)^#
Free IGF-I	-1.59 (-1.78,-1.18)	-1.56 (-1.8-0.97)	-1.29 (-1.8,0.65)
Total IGF-II	0.54 (0.01,1.68)	1.08 (0.39,1.63)	1.71 (1.08,2.41)^#
ALS	-0.94 (-1.59, 0.15)	0.53 (-0.24,1.18)***	0.41 (0.11,1.01)^##
IGFBP-2	-0.48 (-1.42,0.49)	-0.83 (-1.43,-0.07)	-0.47 (-1.19,0.12)
Total IGFBP3	0.15 (-0.71,0.88)	0.24 (-0.32,0.44)	0.34 (-0.13,0.73)
Intact IGFBP3	-1.07 (-1.89,-0.62)	-0.22 (-0.97,0.11)***	-0.09 (-1.01,0.15)^##
Total IGFBP4	-0.24 (-0.64,0.24)	-0.16 (-0.58,0.97)	0.98 (0.45,1.32)^###
Intact IGFBP4	-0.72 (-1.04,-0.23)	-0.47(-0.73,0.45)	-0.13 (-0.47,0.65)
IGFBP5	-0.93 (-1.35,-0.03)	0.45 (-1.8,-0.97)***	1.95 (0.72,2.42)^###
STC1	-1.23 (-1.56,-0.84)	-1.19 (-1.37,-0.94)	-1.26 (-1.35,-0.85)
STC2	-1.31 (-1.97,-0.39)	0.07 (-0.37,0.69)***	0.52 (-0.76,0.90)^###
PAPP-A	0.63 (-0.08,1.33)	0.80 (-0.3,1.27)	0.93 (0.76,1.92)
PAPPA-A2	1.05 (0.68,1.63)	0.49 (-0.07,0.92)***	0.13 (-0.16,0.52)^###
ANOVA p value of onset versus 6 months (P<0.05, * P<0.01, ***P<0.001) and onset versus 12 months (#P<0.05, ## P<0.01, ###P<0.001)

Conclusions: Our preliminary results indicate that implementation of insulin treatment after T1DM onset modifies various members of the circulating IGF system, including those of PAPPA-A2 and STC2. How these modifications correlate with linear growth are under investigation.

ESPE Abstracts

RFC11.2