Age- and sex-specific reference intervals across life span for insulin-like growth factor binding protein 3 (IGFBP-3) and the IGF-I to IGFBP-3 ratio measured by new automated chemiluminescence assays.
BACKGROUND
Measurement of IGF-binding protein-3 (IGFBP-3) can aid the diagnosis of GH-related diseases. Furthermore, epidemiological studies suggest that IGFBP-3 and the molar IGF-I to IGFBP-3 ratio are associated with clinical end points like cancer or cardiovascular disease. However, their clinical use is limited by the lack of validated reference intervals.


OBJECTIVE
The objective of the study was the establishment of age- and sex-specific reference intervals for IGFBP-3 and the molar IGF-I to IGFBP-3 ratio by newly developed automated immunoassays.


METHODS
This was a multicenter study with samples from 11 cohorts from the United States, Canada, and Europe.


METHODS
A total of 14 970 healthy subjects covering all ages from birth to senescence participated in the study.


METHODS
Concentrations of IGFBP-3 and the IGF-I to IGFBP-3 ratio as determined by the IDS iSYS IGF-I and IGFBP-3 assays were measured.


RESULTS
Both the concentration of IGFBP-3 and the IGF-I to IGFBP-3 ratio are mainly determined by age. IGFBP-3 concentrations increase until the age of 22 years, with a plateau being visible between 15 and 25 years. Determined by the high peripubertal peak in IGF-I, the peak in the IGF-I to IGFBP-3 ratio occurs already around the age of 15 years, with a slightly earlier and higher peak in females. Beyond the age of 60 years, IGFBP-3 concentrations remain higher in females, whereas IGF-I as well as the IGF-I to IGFBP-3 ratio remains significantly higher in males.


CONCLUSIONS
We present an extensive set of assay-specific age- and sex-adjusted normative data for concentrations of IGFBP-3 and the molar IGF-I to IGFBP-3 ratio and demonstrate distinct sex specific differences across the life span.
Metabolic Center (N.F., H.W.), Institute of Clinical Chemistry and Laboratory Medicine, and Department of Psychiatry and Psychotherapy (H.J.G.), University Medicine Greifswald, D-17475 Greifswald, Germany; Department of Psychiatry and Psychotherapy (H.J.G.), Helios Hospital Stralsund, D-18437 Stralsund, Germany; Children's Clinic Randers (O.D.W.), DK-8900 Randers, Denmark; Department of Endocrinology, Diabetes, and Nutrition (A.M.A., J.S., A.F.H.P.) and Center for Cardiovascular Research (A.M.A., J.S.), Charité-University Medicine Berlin, D-10117 Berlin, Germany; Department of Clinical Nutrition (A.M.A., A.F.H.P.), German Institute of Human Nutrition Potsdam-Rehbruecke, D-14558 Nuthetal, Germany; Helmholtz Zentrum Muenchen-German Research Center for Environmental Health (R.T.E., A.D.), Institute of Epidemiology II, D-85764 Neuherberg, Germany; Experimental and Clinical Research Center (J.S.), Charité-University Medicine Berlin and Max-Delbrück Centre Berlin-Buch, D-13125 Berlin, Germany; Göteborg Pediatric Growth Research Center (J.R., J.D.), The Sahlgrenska Academy at University of Gothenburg, SE-41685 Gothenburg, Sweden; Institut für Laboratoriumsmedizin (J.K.), Klinische Chemie, Molekulare Diagnostik, University of Leipzig, D-04103 Leipzig, Germany; Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe-Großhadern (C.H.), Klinikum der Universität München, D-81377 Munich, Germany; Endocrine Research Laboratories (M.B., M.B.), Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, D-80336 Munich, Germany; and Medical Research Laboratory (J.F.), Department of Clinical Medicine, Faculty of Health, Aarhus University, and Department of Endocrinology and Internal Medicine (J.F.), Aarhus University Hospital, DK-8000 C Aarhus, Denmark.
Nele
N
Friedrich
Ole D
OD
Wolthers
Ayman M
AM
Arafat
Rebecca T
RT
Emeny
Joachim
J
Spranger
Josefine
J
Roswall
Jürgen
J
Kratzsch
Hans J
HJ
Grabe
Christoph
C
Hübener
Andreas F H
AF
Pfeiffer
Angela
A
Döring
Maximilian
M
Bielohuby
Jovanna
J
Dahlgren
Jan
J
Frystyk
Henri
H
Wallaschofski
Martin
M
Bidlingmaier
D000328:Adult; D000367:Age Factors; D000375:Aging / Q000097:blood*; D005260:Female; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008163:Luminescent Measurements; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D012680:Sensitivity and Specificity; D012737:Sex Factors
D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I