Abstract
OBJECTIVE: This study aimed to investigate the prospective interrelationships among biomarkers that may provide mechanistic insights into obesity-related diseases. METHODS: A total of 850 women in the Nurses' Health Study II with two fasting blood measurements (1996-1999 and 2010-2011) of adiponectin, leptin, soluble leptin receptor, insulin, retinol-binding protein 4, high-sensitivity C-reactive protein (hsCRP), and interleukin-6 were included. Biomarker interrelationships were examined in the following three ways: (1) cross-sectional associations at baseline and follow-up, (2) longitudinal associations of concurrent biomarker changes, and (3) prospective associations of each baseline biomarker with other biomarker changes. RESULTS: In cross-sectional analyses, most biomarkers were correlated after multivariable adjustment including BMI, with the strongest correlations observed between leptin and insulin and between hsCRP and interleukin-6. In longitudinal analyses, similar results were observed after multivariable adjustment including weight change. However, in prospective analyses, only three associations observed in cross-sectional and longitudinal analyses were consistently significant (P < 0.05). Every doubling in baseline adiponectin was associated with -9.0% insulin change. The corresponding estimate was 9.3% for baseline leptin and hsCRP change and 3.1% for baseline hsCRP and leptin change. CONCLUSIONS: Baseline adiponectin concentrations were inversely associated with subsequent insulin change, whereas baseline leptin concentrations were positively associated with hsCRP change and vice versa.