The association between IGF-I/IGFBP-3 and subclinical end points: epidemiology faces the limits.
BACKGROUND
The variation in laboratory measurements represents a challenge in clinical practice and epidemiological research. The use of different analytical platforms might have led to different results, which were often discussed in the interpretation of conflicting results. We aim to study the impact of two different IGF-I and IGF binding protein 3 assays on published epidemiological studies.


METHODS
We compared epidemiological results based on the previous gold standard Nichols Advantage, which is no longer available, with these based on the IDS-iSYS assay. The latter follows the recently proposed Keswick criteria. We reinvestigated published association studies between IGF-I or IGF binding protein 3 and anthropometry, subclinical cardiovascular diseases including intima-media thickness or left ventricular mass index, and hard end points like mortality and single-nucleotide polymorphisms of our genome-wide association study in the Study of Health in Pomerania.


RESULTS
We demonstrated that there are significant differences in the associations of IGF-I measured by the Nichols or IDS-iSYS assay and subclinical outcomes including intima-media thickness and left ventricular mass index. However, concerning hard outcomes like mortality or single-nucleotide polymorphisms, our analyses revealed similar results with comparable regression estimates.


CONCLUSIONS
With our study we queried not only the accuracy of measurement but also the effect of different methods on study results. The establishment of laboratory standards like the Keswick criteria should be enforced to allow reliable comparisons of different methods and thus clinical and epidemiological studies. Single-center studies have to be interpreted carefully. Moreover, to assure the reliability of studies, their results should be replicated in a meta-analysis, and a generated hypothesis by epidemiology should be proven by intervention studies.
Institute of Clinical Chemistry and Laboratory Medicine (C.M., H.W., M.N., N.F.) and Department of Prosthetic Dentistry, Gerodontology, and Biomaterials (S.S.), Center of Oral Health, University Medicine Greifswald, 17475 Greifswald, Germany; Med Clinic I (G.B.), University of Lübeck, 23538 Lübeck, Germany; and Klinik für Innere Medizin I (U.W.), Evangelisches Waldkrankenhaus Spandau, 13589 Berlin, Germany.
Christiane
C
Müller
Henri
H
Wallaschofski
Georg
G
Brabant
Ulrich
U
Wahnschaffe
Stefanie
S
Samietz
Matthias
M
Nauck
Nele
N
Friedrich
D000328:Adult; D000368:Aged; D058070:Asymptomatic Diseases / Q000453:epidemiology*; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000453:epidemiology*; D023381:Endpoint Determination / Q000379:methods* / Q000592:standards; D015340:Epidemiologic Research Design; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D007118:Immunoassay / Q000379:methods / Q000592:standards; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000032:analysis* / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D055815:Young Adult
C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I