Association of inflammation with worsening HOMA-insulin resistance

Abstract

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 loge(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.

Co-effect of insulin resistance and biomarkers of inflammation and endothelial dysfunction on hypertension

“…Xu et al 34 found that CRP suppressed insulin signaling in endothelial cells. The studies by Park et al 7 and Xu et al 34 appear to support the hypothesis that inflammation and endothelial dysfunction introduce IR. Additional results indicate that IR may in turn exacerbate inflammation by increasing cytokine and adipochemokine expression (including TNF-a, interleukin-6, leptin and others), elevating free fatty acid levels, and impairing endothelial nitric oxide synthase activity.…”

“…Ingelsson et al 33 found that vascular cell adhesion molecule-1, E-selectin and CRP were independently associated with metabolic syndrome (MetS) and increased HOMA-IR. Park et al 7 examined the cross-sectional and longitudinal relationships between CRP and IR and found a significant positive association between CRP and IR, in both cross-sectional and longitudinal results, even after adjusting for adiposity measurements and oxidative stress markers. Xu et al 34 found that CRP suppressed insulin signaling in endothelial cells.…”

“…Studies have also shown that inflammation and endothelial dysfunction are not only associated with atherosclerosis, cardiovascular disease and hypertension but also with IR in various settings. [6][7][8][9][10][11] Inflammation and endothelial dysfunction may have an important role in the development of IR. 12 Biomarkers of inflammation and endothelial dysfunction, such as circulating C-reactive protein (CRP), interleukin-6, soluble intercellular cell adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 and soluble E-selectin (sE-selectin), have been reported to be associated with IR.…”

Association of subclinical inflammation with deterioration of glycaemia before the diagnosis of type 2 diabetes: the KORA S4/F4 study

“…There are three previous studies to which our observations may be compared; they assessed changes in glycaemia or HOMA-IR as a surrogate measure of insulin resistance. The first study is the population-based Coronary Artery Risk Development on Young Adults (CARDIA) study, in which hsCRP levels in year 7 of the study were positively associated with HOMA-IR at years 15 and 20 after adjustment for age, sex, race, lifestyle factors, education and the respective baseline HOMA-IR; a similar association was found for hsCRP levels at year 15 and HOMA-IR at year 20 [17]. The mean age of the study population was 32 years at year 7 and 40 years at year 15.…”

“…Only a few prospective studies have tested the hypothesis that circulating levels of immune mediators can predict the deterioration of glycaemic control before the manifestation of type 2 diabetes [15][16][17]. In two studies, deterioration of glycaemia was assessed as the incidence of IFG or IGT [15,16]; another study used increases in HOMA-IR as the outcome [17].…”