The Relationship Between Inflammatory Factors And Abdominal Fat Distribution And Metabolic Status,and Association Studies With The Onset Of Common Chronic Diseases

Objective To investigate the relationships between systemic inflammation index and abdominal fat distribution and metabolic status,and to explore the association of systemic inflammation and the onset of common chronic diseases.Methods This study adopts cross-sectional research and cohort research methods,and takes non-acute infection and trauma patients of Hangzhou metabolic syndrome cohort as the research objects.During the baseline survey in 2010,using face to face questionnaires,physical examination and blood biochemical tests,basic information(age,sex,smoking,alcohol consumption,work and marital status),as well as height,weight,waist circumference(WC),triglycerides(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDL-C),systolic blood pressure(SBP),diastolic blood pressure(DBP)and fasting blood glucose(FPG)of each subject were collected.Twelve serum concentrations of inflammatory factors including interleukin 2(IL-2),interleukin 4(IL-4),interleukin 5(IL-5),interleukin 6(IL-6),tumor necrosis factor α(TNF-α),and interferon α(IFN-α)were measured by flow microsphere arrays in 2021.Two follow-up visits were conducted following baseline surveys.Subjects were measured and measured for SBP,DBP,FPG,TG and HDL-C in 2013 to understand the occurrence of metabolic abnormalities.Data on the incidence of diabetes,cardiovascular diseases and malignancies from 31 December 2010 to 31 December 2020 will be collected in 2022 through the National Chronic Disease Monitoring System.The 75th percentile of each index was divided into high and low level group.Spearman correlation analysis and Logistic regression were used to analyze the associations of each inflammatory factor and abdominal fat distribution,metabolic status and strength of association.Mediating effect model was used to analyze the role of inflammatory factors in the relationship between abdominal fat distribution and metabolic abnormalities.Binary Logistic regression analysis was used to analyze the association study of baseline inflammatory factor levels and the occurrence of metabolic abnormalities after follow-up.Hazard ratio(HR)and the 95%confidence interval(CI)were calculated for associations of baseline inflammatory factor levels with common chronic disease after follow-up using the Cox proportional hazards model.Results(1)Baseline characteristics:701 subjects(58.8%women)were included,with a mean age of 74.9±7.0 years.Metabolism abnormalities accounted for 44.9%of the subjects.Men had high proportion of smoking,drinking alcohol and drinking tea than women(P<0.05).Body mass index(BMI),WC,visceral adipose tissue(VAT),SBP,DBP,FPG and TG levels were higher in men than in women.While the Subcutaneous adipose tissue(SAT)and HDL-C levels were lower in men than in women(P<0.05).The prevalence of type 2 diabetes,hypertension and hyper-triglyceridemia was higher in men than in women(P<0.05).(2)Description of baseline inflammatory factors:the levels of different inflammatory factors in the population varies greatly.IL-5,IL-6,interleukin 8(IL-8),and interleukin 10(IL-10)levels were higher in men than women(P<0.05).In menopausal women,IL-6(median was 4.29 Pg/ml)was higher than in non-menopausal women(median was 2.80 Pg/ml)(P<0.05).IL-5,IL-6,and IFN-α were positively associated with age(r were 0.16,0.18,and 0.12,respectively,P<0.05)in men.IL-5,IL-6,IL-10,and interferon γ(IFN-γ)were positively associated with age(r were 0.11,0.12,0.13,and 0.13,respectively,P<0.05)in women.Low to moderate positive associations were observed among inflammatory factors such as interleukin 1β(IL-1β),IL-2,IL-4,and IFN-γ.Their correlation coefficients were between 0.02 and 0.60.(3)The relationships between inflammatory factors and abdominal fat distribution were explored after stratifying by age and sex.The results showed that in men,SAT was positively correlated with IL-6(r=0.17,P<0.05),VAT was significantly and positively associated with IFN-α(r=0.11,P<0.05),and was nominal and marginal negative associated with IL-1β(r=-0.12,P=0.083);VAT was positively associated with IL-6,IL-10,and IFN-α in women(r=0.14,0.19,and 0.12,respectively,P<0.05).Continuous variables of inflammatory factors,SAT and VAT were transformed into dichotomous variables by P75 and classified into high and low two levels.After adjusting for age and sex stratification by using a binary Logistic regression model,the results showed a negative correlation between high SAT and high IL-1β in man,OR(95%CI)was 0.50(0.24,0.94),high VAT was positively associated with high IFN-α,OR(95%CI)was 1.72(1.44,3.22);High SAT was positively associated with high IL-6,IL-8,and TNF-α in women,OR(95%CI)was 1.76(1.06,2.92),2.05(1.23,3.41)and 1.62(1.15,2.74),high VAT was positively associated with high IL-2 and IL-10,OR(95%CI)was 1.86(1.09,3.19)and 1.57(1.16,2.56).(4)After adjusting for age and sex stratification,high IL-1β was inversely associated with high TG in man,OR(95%CI)was 0.44(0.25,0.80);High IL-10 was positively associated with high SBP in women,OR(95%CI)was 1.71(1.02,2.86),high IL-4,IL-10,IFN-γ,and IFN-α were positively associated with high TG,OR(95%CI)were 1.74(1.06,2.85),1.70(1.04,2.80),1.90(1.12,3.20)and 1.83(1.11,3.03)respectively,high IL-10,interleukin 17(IL-17)and IFN-α were positively associated with low HDL-C,OR(95%CI)were 2.05(1.22,3.44),2.08(1.20,3.61)and 2.01(1.20,3.36)respectively.No other inflammatory factors was found to be associated with metabolic component abnormalities(P>0.05).Two or more abnormalities of metabolic components(SBP,DBP,FPG,TG,and HDL-C)were defined as metabolic abnormalities.After adjusting for age and stratifying by sex,the risk of metabolic abnormalities in man was inversely associated with IL-1β,OR(95%CI)was 0.49(0.28,0.87),a nominal and marginal negative relationship with IL-4 were observed,with an OR(95%CI)value of 0.59(0.34,1.00),P=0.054.The risk of metabolic abnormalities in women was positively associated with IL-10,OR(95%CI)was 2.34(1.45,3.78).(5)The relationship between inflammatory factors and different obesity metabolic phenotypes:IL-6 and IL-10 continuous variables were transformed into dichotomous variables according to P75,which were divided into high and low levels.After adjusting for age and sex stratification by using multivariate Logistic regression model,results showed that high IL-6 levels were associated with the risk of metabolically normal and overweight or obesity(MNO)in women,OR(95%CI)were 1.36(1.25,2.46),respectively;High IL-10 was associated with the risk of metabolically abnormal and normal weight(MANW)and MAO in women,OR(95%CI)were 2.31(1.12,4.76)and 4.21(2.18,8.13),respectively.IL-6 and IL-10 were not found to be associated with different obesity metabolic phenotypes in men(P>0.05).(6)Inflammatory factors play a partial mediating role in the relationship between abdominal fat distribution and metabolic abnormalities:Adjusting for age using mediating analytical models,the role of inflammatory factors in the association of SAT and VAT with metabolic abnormalities was analyzed.The results showed that IL-10 only partially mediated the association between VAT and metabolic abnormalities in the population,and mediated effect of 4.06%.After sex stratification,this mediated effect was observed only in females,and mediated effect of 4.60%.(7)Association studies of baseline inflammatory cytokine levels and the onset of common chronic diseases:Follow-up 3 years later revealed 50 cases of new metabolic abnormalities in the cohort,with an incidence of 28.4%.A binary Logistic regression model was used after adjusting for age and sex.The results showed that high levels of IL-6 and IL-8 may were risk factors for metabolic abnormalities,with OR(95%CI)values of 3.82(1.84,7.96)and 2.61(1.24,5.45).The effect of inflammation levels on the onset of common chronic diseases:after 10 years of follow-up,the number of type 2 diabetes,cardiovascular and cerebrovascular diseases and cancer in the cohort were 43 cases,36 cases and 24 cases,respectively,and the incidence densities were 8.33‰,5.45‰ and 3.49‰,respectively.After adjusting for the age and sex in the Cox proportional hazards regression model,the results showed that The risk of diabetes in the baseline high-level group IL-6 and IL-8 was 1.92 times higher than that in the low-level group(HR=1.95,95%CI=1.06-3.58)and 1.81 times(HR=1.81,95%CI=0.98-3.36);the risk of the baseline high level IL-12P70 was 1.87 times higher than the low level(HR=1.87,95%CI=0.90-3.91),with a P-value close to 0.05;no inflammatory factor was associated with the risk of malignancy(P>0.05).Conclusion Abdominal fat distribution(SAT and VAT)is associated with inflammatory levels,The level of inflammation is associated with metabolic abnormalities and with different obesity metabolic phenotypes.High inflammatory levels at baseline increase the risk of chronic diseases such as metabolic abnormalities,diabetes,cardiovascular and cerebrovascular diseases.