Insulin resistance and inflammation mediate the association of abdominal obesity with colorectal cancer risk

Abstract

BackgroundThe close association of abdominal obesity rather than general obesity with colorectal cancer (CRC) risk might be mediated by IR and inflammation, which has never been systematically explored in large-scale prospective studies.MethodsWe prospectively examined the mediation effects of the fasting triglyceride-glucose (TyG) index and C-reactive protein (CRP) on the associations of obesity (general and abdominal) with CRC risk among 93,659 participants. We used the Cox proportional hazards regression models and subgroup analyses to evaluate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) of CRC. The CAUSALMED procedure was used to perform the mediation analyses.ResultsDuring 13.02 years of follow-up, a total of 586 CRC cases were verified. Male participants with general obesity and abdominal obesity had a 1.29-fold and a 1.28-fold increased risk of CRC. However, a significant association was only observed among female individuals with abdominal obesity. Both TyG index and CRP were associated with an elevated risk of CRC, and A significant interaction between the TyG index and CRP was found for the risk of CRC (P for interaction<0.05). CRP and the TyG index significantly mediated the positive association between abdominal obesity and CRC risk.ConclusionCRP and TyG index increased the risk of CRC independently and synergistically. Mediation effects of CRP and the TyG index were found for the association between abdominal obesity and CRC risk.

Adherence to the Paleolithic diet and Paleolithic-like lifestyle reduce the risk of colorectal cancer in the United States: a prospective cohort study

“…In another pooled cross-sectional study of a population undergoing elective outpatient colonoscopy (n = 646), Whalen et al reported that adherence to PD may reduce systemic inflammation and oxidative stress levels in humans [ 23 ]. This finding partially supports our conclusion since the progression of CRC is typically associated with inflammation and oxidative stress [ 24 – 26 ]. In addition, epidemiological studies have increasingly confirmed the potential association between adherence to the PD and a reduced risk of other cancers.…”

Association between higher triglyceride glucose index and increased risk of osteoarthritis: data from NHANES 2015–2020

“…It has been shown in earlier research that inflammation and the TyG index are highly related. Li et al [ 23 ] demonstrated that higher levels of inflammation and the TyG index, both individually and in combination, increased the risk of colorectal cancer. Moreover, Yan et al [ 24 ] elucidated that among Americans under 60 with average weight and no diabetes, the TyG index was positively linked with arthritis.…”

Temporal relationship between inflammation and metabolic disorders and their impact on cancer risk

“…Similar to our study, Lee et al also demonstrated that while combined exposure to systemic inflammation and insulin resistance can effectively predict cancer-related mortality in patients, they found that the predictive ability of inflammation remained regardless of insulin resistance levels [ 34 ]. Li et al [ 35 ] showed that metabolic disorders synergistically increase the risk of colorectal cancer and abdominal obesity induced by inflammation, exerting a significant mediating effect. These findings, including both basic and clinical research, collectively suggest that inflammation is more likely to be the initiating factor for metabolic dysregulation and disease than the reverse.…”