Aims/hypothesis: We examined the cross-sectional and longitudinal relationships between C-reactive protein (CRP), a marker of low-grade inflammation, and insulin resistance and whether the association was independent of obesity and oxidative stress. Methods: CRP and insulin resistance (homeostasis model assessment of insulin resistance [HOMA-IR]) data were obtained in a population-based, prospective observational study, Coronary Artery Risk Development in Young Adults (CARDIA), during 1992-2006. Results: CRP showed a significant positive association with insulin resistance, both cross-sectionally and longitudinally (5 year follow-up). The estimated increment in HOMA-IR was 0.34 log e (pmol/l×[mmol/l]/156.25) (p value for trend <0.0001) in the highest vs lowest CRP quartiles in cross-sectional analysis, whereas the corresponding estimate was 0.12 (p trend <0.0001) in the highest vs lowest CRP quartiles longitudinally over 5 years. The gradient of HOMA-IR across CRP was attenuated but remained statistically significant after controlling for body fat measurements (0.06 in the highest vs lowest CRP in both cross-sectional [p value for trend=0.001] and longitudinal analyses [p value for trend=0.01]), and was little changed by further adjustment for oxidative stress markers (F2-isoprostanes and oxidised LDL). There were consistent increments in the levels of HOMA-IR with increasing concentrations of CRP over time. In contrast, higher HOMA-IR did not predict future increases in CRP. Findings were similar using fibrinogen as the predictor variable. Conclusions/interpretation: Although a substantial portion of this association was explained by obesity, CRP was independently related to concurrent and future insulin resistance.
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Acknowledgements Source of funding: this research was supported by contracts N01-HC-95095, N01-HC-48047, N01-HC-48048, and N01-HC-48049 and a grant R01-HL-53560, all from the National Heart, Lung, and Blood Institute, National Institutes of Health, Coronary Artery Risk De velopment in Young Adults (CARDIA study).
- Insulin resistance