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

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at