Impact of systemic inflammation on the relationship between insulin resistance and all-cause and cancer-related mortality

Abstract

Background: Insulin resistance and inflammation play an important role in a variety of chronic diseases.

Objective: We investigated the influence of systemic inflammation on the relationship between insulin resistance and mortality risk in apparently healthy adults.

Methods: This study examined the mortality outcomes for 165,849 Koreans enrolled in a health-screening program. The subjects were divided into four groups according to their homeostatic model assessment of insulin resistance (HOMA-IR) and high-sensitivity C-reactive protein (hs-CRP) levels: group 0, HOMA-IR <75% and hs-CRP <2.0mg/L; group 1, HOMA-IR ≥75% and hs-CRP <2.0mg/L; group 2, HOMA-IR <75% and hs-CRP ≥2.0mg/L; and group 3, HOMA-IR ≥75% and hs-CRP ≥2.0mg/L. The Cox proportional hazard models were used to assess hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause, cardiovascular disease, and cancer-related mortality.

Results: During the follow-up period of 1,417,325.6person-years, a total of 1316 deaths (182 from cardiovascular disease) occurred. The multivariate-adjusted HRs for all-cause mortality were significantly higher in groups 2 (HR 1.40; 95% CI: 1.19-1.64) and group 3 (HR 1.68; 95% CI: 1.34-2.10) than that in group 0. For cardiovascular mortality, the sex-adjusted hazards were also significantly higher in groups 2 and 3 than that in group 0; however, this increased risk disappeared during multivariate analysis. Groups 2 and 3 had significantly higher risk for cancer-related mortality than group 0, with multivariate-adjusted hazard ratios of 1.48 (95% CI: 1.18-1.86) and 1.84 (95% CI: 1.35-2.51), respectively.

Conclusions: Systemic inflammation can be used to stratify the subjects according to the all-cause and cancer-related mortality risks, irrespective of the insulin-resistance status. And this tendency is most pronounced in cancer-related mortality.

Keywords: HOMA-IR; High-sensitivity C-reactive protein; Inflammation; Insulin resistance; Mortality.