Background: Most prior studies on associations of adiposity-associated biomarkers are cross-sectional. Understanding their longitudinal interrelationships may provide mechanistic insights into biologic pathways that lead to cardiometabolic diseases.
Methods: We included 850 healthy women in the Nurses’ Health Study II (mean age: 45y) who provided two blood samples in 1996-1999 and 2010-2011 and measured plasma concentrations of adiponectin (ADPN), leptin, soluble leptin receptor, insulin, retinol binding protein-4, high-sensitivity C-reactive protein (hsCRP), and interleukin-6 (IL-6). All biomarkers were log2-transformed. Spearman partial correlations were used to examine cross-sectional biomarker associations at baseline and follow-up. Multivariable general linear models were used to evaluate associations of each biomarker change over 13 years with (1) concurrent changes in other biomarkers (change-change) and (2) baseline levels of other biomarkers (baseline-change).
Results: In cross-sectional analyses, most biomarkers were correlated after multivariable adjustment including BMI (p<0.05) both at baseline and follow-up, with the strongest associations observed between leptin/insulin and hsCRP/IL-6. There were similar associations in the change-change analysis with multivariable adjustment including weight change. However, only two associations were consistently present in the baseline-change analysis after multivariable adjustment including baseline BMI. Every doubling in baseline hsCRP was associated with 3.1% leptin change (p=0.01), whereas every doubling in baseline ADPN was associated with -9.2% insulin change (p=0.01). Notably, baseline insulin was not associated with other biomarker changes.
Conclusions: While most adiposity-associated biomarkers were interrelated both cross-sectionally and longitudinally, our results suggest that baseline hsCRP and ADPN were strong predictors for long-term changes in leptin and insulin, respectively.
M. Baden: Other Relationship; Self; Manpei Suzuki Diabetes Foundation. F. Hu: None. T. Huang: None.
National Institutes of Health; Manpei Suzuki Diabetes Foundation