Prospective Study of Long-Term Interrelationships Among Adiposity-Associated Biomarkers in Women

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.

Figure 1.. Associations between each biomarker changes with other biomarker changes.

Values are multivariable-adjusted percent differences of biomarker changes per doubling of percent changes in each biomarker concentration. Error bars represent 95% confidence intervals. *indicates p<0.05, **indicates significant association after Bonferroni correction (p<0.05/6=0.008).

Figure 2.. Associations between each baseline biomarker concentration with other biomarker changes.

Values are multivariable-adjusted percent differences of biomarker changes per doubling in each baseline biomarker concentration. Error bars represent 95% confidence intervals. *indicates p<0.05, **indicates significant association after Bonferroni correction (p<0.05/6=0.008), and ^†indicates the consistent associations with cross-sectional and longitudinal analyses.