Jesper S Sorensen1, Niels H Birkebaek, Mette Bjerre, Flemming Pociot, Kurt Kristensen, Anne Soee Hoejberg, Jan Frystyk. 1. Departments of Pediatrics (J.S.S., N.H.B., K.K.) and Endocrinology and Internal Medicine (J.F.), Aarhus University Hospital, and The Medical Research Laboratory (M.B., J.F.), Department of Clinical Medicine, Faculty of Health, Aarhus University, DK-8000 Aarhus C, Denmark; Department of Pediatrics (J.S.S.), Randers Regional Hospital, DK-8930 Randers, Denmark; Department of Pediatrics E (F.P.), Herlev University Hospital, DK-2730 Herlev, Denmark; and Department of Pediatrics (A.S.H.), Aalborg University Hospital, DK-9000 Aalborg, Denmark.
Abstract
CONTEXT: C-peptide-positive adults with type 1 diabetes (T1D) have higher circulating total and free IGF-1 and lower IGF binding protein 1 (IGFBP-1) than C-peptide-negative patients. Whether this is also the case in children remains unknown. OBJECTIVE: The objective of the study was to examine the IGF system in children/adolescents with and without residual β-cell function (RBF). DESIGN AND PATIENTS: This was a cross-sectional study containing 136 prepubertal (hereof 15 RBF positive) and 206 pubertal (hereof 42 RBF positive) children/adolescents with T1D for 3-6 years as well as 40 prepubertal and 30 pubertal healthy controls. RBF was evaluated by meal-stimulated C-peptide. MAIN OUTCOME MEASURES: Fasting serum levels of bioactive IGF (ie, the ability of serum to activate the IGF-1 receptor in vitro), total IGF-1, total IGF-2, and IGFBP-1 and -3. RESULTS: Irrespective of pubertal status, patients with T1D showed lower bioactive IGF and total IGF-1, but higher IGFBP-1 as compared with controls (P < .05). When stratified according to RBF status, a positive RBF was associated with normalization of all IGF-related peptides but IGFBP-1 in prepubertal children (P < .05), whereas none of the IGF components were normalized in prepubertal, RBF-negative children. In pubertal children, total IGF-1 and bioactive IGF remained subnormal and IGFBP-1 supranormal, irrespective of RBF status (P < .05). CONCLUSION: Independent of pubertal status, T1D was associated with an abnormal IGF system. However, a positive RBF status appeared important but only in prepubertal children, in whom all IGF components but IGFBP-1 were normalized. We speculate that the pubertal GH surge induces insulin resistance, which overrides the stimulatory effect that an RBF may exert on the liver-derived IGF system.
CONTEXT: C-peptide-positive adults with type 1 diabetes (T1D) have higher circulating total and free IGF-1 and lower IGF binding protein 1 (IGFBP-1) than C-peptide-negative patients. Whether this is also the case in children remains unknown. OBJECTIVE: The objective of the study was to examine the IGF system in children/adolescents with and without residual β-cell function (RBF). DESIGN AND PATIENTS: This was a cross-sectional study containing 136 prepubertal (hereof 15 RBF positive) and 206 pubertal (hereof 42 RBF positive) children/adolescents with T1D for 3-6 years as well as 40 prepubertal and 30 pubertal healthy controls. RBF was evaluated by meal-stimulated C-peptide. MAIN OUTCOME MEASURES: Fasting serum levels of bioactive IGF (ie, the ability of serum to activate the IGF-1 receptor in vitro), total IGF-1, total IGF-2, and IGFBP-1 and -3. RESULTS: Irrespective of pubertal status, patients with T1D showed lower bioactive IGF and total IGF-1, but higher IGFBP-1 as compared with controls (P < .05). When stratified according to RBF status, a positive RBF was associated with normalization of all IGF-related peptides but IGFBP-1 in prepubertal children (P < .05), whereas none of the IGF components were normalized in prepubertal, RBF-negative children. In pubertal children, total IGF-1 and bioactive IGF remained subnormal and IGFBP-1 supranormal, irrespective of RBF status (P < .05). CONCLUSION: Independent of pubertal status, T1D was associated with an abnormal IGF system. However, a positive RBF status appeared important but only in prepubertal children, in whom all IGF components but IGFBP-1 were normalized. We speculate that the pubertal GH surge induces insulin resistance, which overrides the stimulatory effect that an RBF may exert on the liver-derived IGF system.
Authors: Andrew Dauber; María T Muñoz-Calvo; Vicente Barrios; Horacio M Domené; Soren Kloverpris; Clara Serra-Juhé; Vardhini Desikan; Jesús Pozo; Radhika Muzumdar; Gabriel Á Martos-Moreno; Federico Hawkins; Héctor G Jasper; Cheryl A Conover; Jan Frystyk; Shoshana Yakar; Vivian Hwa; Julie A Chowen; Claus Oxvig; Ron G Rosenfeld; Luis A Pérez-Jurado; Jesús Argente Journal: EMBO Mol Med Date: 2016-04-01 Impact factor: 12.137