Association Of Nonalcoholic Fatty Liver Disease With Cardiometabolic Disorders And Related Risk Factors

Part OneThe triglyceride and glucose index(TyG)is an effective biomarker to identify nonalcoholic fatty liver diseaseObjective:The triglyceride and glucose index(TyG)has been proposed as a marker of insulin resistance.We aimed to investigate the ability of TyG,through comparing with the predictive value of ALT,to identify individuals at risk for NAFLD.Methods:A cross-sectional study was conducted in a Chinese health examination cohort of 10 761 people aged above 20 years.NAFLD was diagnosed by ultrasonography.Logistic regression analysis and receiver operating characteristic(ROC)curve analysis were performed to evaluate the ability of TyG and ALT in identifying NAFLD.Results:(1)The prevalence of NAFLD was increased with both TyG and ALT levels.With the first quartile as reference,the fourth quartile of TyG and ALT had a 6.3-and 3.7-fold increase in NAFLD prevalence.(2)Compared with the participants in the lowest quartile of TyG.the adjusted odds ratios(ORs)and 95%confidence intervals(CIs)for NAFLD were 1.8(1.5-2.1),3.0(2.5-3.5).and 6.3(5.3-7.5)for those in the second,the third,and the fourth quartile of TyG,whereas the corresponding ORs(95%CI)for NAFLD were 1.5(1.3-1.7),1.9(1.6-2.2),and 3.1(2.6 3.7)for the upper three quartiles of ALT.These results suggested that TyG was superior to ALT in association with NAFLD risk.(3)The association persisted in different sex-,age-,BMI-,blood pressure-,uric acid-,and white cell counts-subgroups.(4)According to the ROC analysis,the optimal cut-off point of TyG for NAFLD was 8.5 and the area under the ROC curve(AUC)was 0.782(95%CI 0.773-0.790),with 72.2%and 70.5%sensitivity and specificity,respectively.The AUC of TyG was larger than that of ALT(0.715[95%CI 0.705-0.725],P for difference<0.0001),whereas the largest AUC was obtained when adding TyG to ALT(0.804[95%CI 0.795-0.812],P for difference<0.0001).Conclusions:TyG was positively and independently associated with NAFLD risk.TyG performed better than ALT to identify individuals at risk for NAFLD.A TyG threshold of 8.5 was highly sensitive for detecting NAFLD subjects and may be suitable as a diagnostic criterion for NAFLD in Chinese adults.Part TwoCombined effect of obesity and elevated uric acid on nonalcoholic fatty liver disease and hypertriglyceridemiaObjective:Elevated uric acid(UA)is associated with metabolic syndrome(MetS),but the association is often confounded by the shared background of obesity.Nonalcoholic fatty liver disease(NAFLD)is considered as the hepatic manifestation of MetS.Recent studies have demonstrated a close relationship between UA and NAFLD.We sought to explore the modifying effects of obesity on the association between UA,MetS components,and NAFLD.Methods:We conducted a cross-sectional study in a Chinese population of 10,069 participants aged>20 years.Multiplicative interaction between obesity(BMI>25kg/m2)and elevated UA was assessed using an interaction term in logistic regression analysis.The presence of additive interaction was assessed based on the relative excess risk due to the interaction(RERI)and the attributable proportion due to the interaction(AP).Results:(1)There was no evidence of a multiplicative interaction between obesity and elevated UA on risk for MetS components and NAFLD.(2)There was strong additive interaction between obesity and elevated UA with regard to NAFLD(RERI of 6.47[95%Cl 3.42-9.53]for men and 5.87[1.55-10.19]for women)and hypertriglyceridemia(RERI of 1.38[0.57-2.20]for men and 1.38[0.08-2.67]for women).In addition,42%and 36%of the increased cdds of NAFLD for men and women,respectively,can be explained by an interaction between obesity and elevated UA(AP of 0.42[95%CI 0.30-0.54]for men and 0.36[0.17-0.55]for women).Similarly,the interaction accounted for 27%and 26%of the increased risk of hypertriglyceridemia for men and women(AP of 0.27[0.14-0.41]for men and 0.26[0.06-0.47]for women).Conclusions:In this population,obesity and elevated UA synergistically interacted to increase the risk for NAFLD and hypertriglyceridemia.Part ThreeAssociation of nonalcoholic fatty liver disease with cardiometabolic disorders and related risk factorsObjective:Nonalcoholic fatty liver disease(NAFLD)is closely associated with insulin resistance and metabolic syndrome(MetS),and able to predict the risk for type 2 diabetes mellitus and cardiovascular disease.The objective of our study is(1)to investigate the association of NAFLD and its severity with cardiometabolic disorders,(2)to assess the effect of sex,age,and BMI on the association between NAFLD and cardiometabolic disorders,and(3)to compare the ability of NAFLD and BMI in identifying MetS.Methods:We used data from health examination of all employees and retired workers aged between 20-100 years at the Wuhan Iron and Steel Company(WISCO)General Hospital in 2009.The anthropometry and biochemical measurements were obtained for analysis.NAFLD was diagnosed by ultrasonography.Association of NAFLD and cardiometaboli disorders was identified using logistic regression analysis.Results:(1)Compared with non-NAFLD individuals,NAFLD participants had significantly higher prevalence of cardiometabolic disorders,including obesity,components of MetS,diabetes mellitus,hypertension dyslipidemia and hyperuricemia(all P<0.0001).(2)NAFLD conferred a 4.06-fold increased risk of the presence of metabolic abnormality(OR 5.06,95%CI:4.62-5.54),a 2.53-fold increased risk of the presence of diabetes mellitus(OR 3.53,95%CI:2.93-4.25),a 1.67-fold increased risk of the presence of hypertension(OR 2.67,95%CI:2.43-2.92),a 2.76-fold increased risk of the presence of dyslipidemia(OR 3.76,95%CI:3.45-4.10),and a 2.32-fold increased risk of the presence of hyperuricemia(OR 3.32,95%CI:2.92-3.78),as compared with non-NAFLD participants.The association persisted after adjusted for potential confounders,such as sex,age,BMI,alanine aminotransferase(ALT),and white blood cell counts.(3)Compared to non-NAFLD individuals,the risk of developing cardiometabolic disorders significantly increased in mild NAFLD patients,with an even higher risk in moderate-to-severe NAFLD patients(P for trend<0.0001).(4)Elevated ALT was associated with increased risk of cardiometabolic disorders except for diabetes and hypertension in non-NAFLD participants.NAFLD patients with elevated ALT had the highest risk for all cardiometabolic disorders.(5)In all subgroups classified by sex,age,and BMI,NAFLD was positively and independently associated with all cardiometabolic disorders.However,the association was stronger in women than men.in people with age<50 years than in those with age>50 years,and in nonobese than in obese subjects(all P for interaction<0.05).(6)There was an excellent agreement of BMI-and NAFLD-based identification of MetS.However,the NAFLD-diagnosed MetS individuals were in worse metabolic characteristics(triglycerides,triglyceride/high density lipoprotein-cholesterol ratio,white blood cell counts,uric acid,alanine aminotransferase)than BMI-diagnosed MetS patients(all P<0.05).Conclusions:NAFLD was independently associated with increased risk of cardiometabolic disorders.The association was affected by the severe pattern of NAFLD,ALT levels,and sex,age,as well as BMI levels.