ObjectiveTo investigate the associations of multiple glycolipid metabolic indicators and their cumulative abnormality burden with incident colorectal cancer risk in a general population-based prospective cohort, and to examine the mediating role of glycolipid metabolic abnormalities in the relationships between smoking, alcohol consumption, physical activity, and colorectal cancer incidence. MethodsA total of 17 897 eligible participants recruited from the Taizhou Cohort between 2011 and 2014 were included. Cox proportional hazards regression models were used to assess the associations of conventional and derived glycolipid indicators, as well as a glycolipid abnormality index constructed from total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fasting plasma glucose, and insulin, with incident colorectal cancer risk. Restricted cubic spline models were applied to evaluate dose-response relationships for major indicators. Receiver operating characteristic curves were generated to compare predictive performance across indicators. Mediation analyses were conducted to assess the mediating effects of the glycolipid abnormality index on the associations of smoking, alcohol consumption, and physical activity with colorectal cancer incidence. ResultsDuring a median follow-up of 11.2 years, 102 incident colorectal cancer cases were identified, with an incidence density of 51.2 per 100 000 person-years. After adjustment for potential confounders, Cox proportional hazards regression analyses showed that decreased high-density lipoprotein cholesterol was associated with a 1.74-fold higher risk of colorectal cancer (HR=1.74, 95%CI: 1.03‒2.95), elevated low-density lipoprotein cholesterol was associated with a 1.78-fold higher risk (HR=1.78, 95%CI: 1.05‒3.02), and abnormal fasting plasma glucose was associated with a 1.86-fold higher risk (HR=1.86, 95%CI: 1.15‒3.02). Triglycerides and fasting plasma glucose showed an approximately linear increasing association with colorectal cancer risk in multivariable restricted cubic spline models. The glycolipid abnormality index showed a clear gradient association with colorectal cancer risk; participants with three or more abnormal indicators had a 3.08-fold higher risk than those without abnormalities (HR=3.08, 95%CI: 1.60‒5.92). The area under the curve was 0.795, higher than that of individual glycolipid indicators and other combined indices, and gender-stratified analyses showed generally consistent patterns. Glycolipid metabolic abnormalities partially mediated the associations of smoking, alcohol consumption, and physical activity with colorectal cancer incidence, with mediation proportions of 8.33%, 9.45%, and 9.04%, respectively. ConclusionGlycolipid metabolic abnormalities are associated with an increased risk of incident colorectal cancer. The glycolipid abnormality index shows an increasing relationship with colorectal cancer risk and demonstrates better discrimination, and it partially mediates the associations of smoking, alcohol consumption, and physical activity with colorectal cancer incidence in the overall population.

Diabetes mellitus type 2(T2DM)is a common chronic metabolic disease,compared to non-diabetics,T2DM patients have a higher risk of heart disease,and their risk of vascular diseases is twice that of non-diabetic individu-als.Multiple clinical trials have confirmed that glucagon-like peptide-1 receptor agonists(GLP-1RA),in addition to their function of lowering blood glucose,can also decrease the risk of cardiovascular events in T2DM patients.This article re-views the mechanisms of GLP-1RA-mediated cardioprotection.It provides a comprehensive review of the recent progress in GLP-1RA-mediated cardiac protective mechanisms,elaborating on the protective effects of GLP-1RA on specific heart cell and further discussing its impact on heart failure(HF),provide assistance for clinical treatment of diabetic cardiomyopathy.

Diabetes mellitus type 2(T2DM)is a common chronic metabolic disease,compared to non-diabetics,T2DM patients have a higher risk of heart disease,and their risk of vascular diseases is twice that of non-diabetic individu-als.Multiple clinical trials have confirmed that glucagon-like peptide-1 receptor agonists(GLP-1RA),in addition to their function of lowering blood glucose,can also decrease the risk of cardiovascular events in T2DM patients.This article re-views the mechanisms of GLP-1RA-mediated cardioprotection.It provides a comprehensive review of the recent progress in GLP-1RA-mediated cardiac protective mechanisms,elaborating on the protective effects of GLP-1RA on specific heart cell and further discussing its impact on heart failure(HF),provide assistance for clinical treatment of diabetic cardiomyopathy.