Association Between Triglyceride-Glucose Index And Risk Of Metabolic-Associated Diseases

Part One Association between triglyceride-glucose index and risk of incident diabetes:a cohort studyObjective:Insulin resistance(IR)is the earliest metabolic abnormality and an important pathogenic mechanism of type 2 diabetes.The hyperinsulinemic-euglycemic clamp(HIEC)technique continues to be the gold standard for quantitative IR,whereas it is costly and time-consuming to apply in clinical practice.Homeostasis model assessment-IR(HOMA-IR)is recognized as an alternative index of IR.However,insulin measurement in the general population remains challenging.The triglycerideglucose index(TyG index),derived from triglyceride(TG)and fasting plasma glucose(FPG),has been found to be well associated with both HIEC and HOMA-IR,and has proved to be a simple and reliable alternative to IR.As a non-insulin based index,TyG index is easily and inexpensively determined,which is advantageous in clinical and epidemiological research.However,evidence on the association between TyG index and diabetes risk remains limited,especially in Chinese population.Therefore,this study sought to explore the association of baseline TyG index with diabetes risk in Chinese adults.Methods:This study was a retrospective cohort study across 32 locations in 11 cities,including participants who received at least two health checks between 2010 and 2016.A total of 201,298 non-diabetic adults(54.3%male)aged≥20 years were included,and the average age was 42.08±12.67 years.TyG index was calculated as Ln[FPG(mg/d L)×Fasting TG(mg/d L)/2].Cox proportion-hazard model was employed to evaluate the independent impact of baseline TyG index on diabetes risk.Taking TyG index as a categorical variable(TyG index quartiles),sensitivity analysis was implemented to test the robustness of results.Subgroup analyses were performed according to stratified variables(gender,age,body mass index,blood pressure,smoking,drinking,and family history of diabetes)to assess the effect of stratification factors on the relationship of TyG index with diabetes risk.Additionally,a generalized additive model was applied to explore the nonlinear relationship of TyG index with diabetes risk.Kaplan-meier curves were used for generating cumulative event rates,and log-rank tests were used to compare differences among groups.Results:During an average follow-up of 3.12 years,among 201,298individuals aged≥20 years,3389 subjects developed diabetes.After adjusting for potential confounders,elevated TyG index was independently associated with greater risk of incident diabetes(HR 3.34,95%CI 3.11-3.60).Compared with the lowest quartile,those with the highest TyG quartile had a 6.26 times risk of diabetes(HR 6.26,95%CI 5.15-7.60).Moreover,a nonlinear relationship was observed between TyG index and diabetes risk,which had an inflection point of TyG index was 8.58.The effect sizes and the confidence intervals on the left and right sides of the inflection point were 2.94(2.68-3.32)and 4.18(3.36-4.96),respectively.Subgroup analysis revealed the positive association was stronger in females,young adults,and subjects with normal body mass index(BMI)or systolic blood pressure(SBP).Summary:This study manifested an independent positive association between TyG index and risk of diabetes in Chinese adults,and a non-linear relationship was found between TyG index and risk of diabetes,and saturation threshold provided a more accurate basis for screening high-risk individuals.Part Two Association between triglyceride-glucose index and risk of Metabolic syndrome:a cohort studyObjective:Metabolic syndrome(Met S)is a cluster of metabolic disorders characterized by central obesity,hyperglycemia,hypertriglyceridemia,low high-density lipoprotein cholesterol and hypertension,and IR is currently recognized as the core pathogenesis of Met S.Effective measurement of IR can improve the predictive power of Met S.TyG index has been recommended as a reliable alternative indicator of IR.However,studies on the association between TyG index and Met S risk are relatively rare.Thus,this study aimed to investigate the relationship of TyG index with risk of Met S in a large cohort in Chinese population.Methods:This study was a retrospective cohort study using professional bus drivers who underwent two health checks in a health examination center of Hebei General Hospital in 2017 and 2020,respectively.A total of 6893adults aged≥20 years without metabolic syndrome were included,of which78.1%were men,with an average age of 41.23±7.78 years.The standardized questionnaire,physical examination form and biochemical index form were used to collect demographic,clinical disease information and blood biochemical indexes.TyG index was calculated as Ln[FPG(mg/d L)×Fasting TG(mg/d L)/2].The diagnosis of metabolic syndrome was based on the 2013Diagnostic criteria for metabolic syndrome of the Diabetes Society of the Chinese Medical Association.The Cox proportion-hazard model was used to investigate the association of baseline TyG index with the risk of Met S.Generalized additive models were applied to identify non-linear relationships between TyG index and Met S risk.If a non-linear correlation was observed,a two-piecewise linear regression model was performed to calculate the threshold effect of the TyG index on incident of Met S in terms of the smoothing plot,and the recursive method automatically calculated the inflection point.Receiver operating characteristic curve analysis(ROC curve)was conducted to estimate the predictive power of TyG index and other risk factors for Met S.Results:After 3 years of follow-up,2142 of 6893 subjects developed Met S.After adjusting for potential confounders,elevated TyG index were independently associated with greater risk of Met S(HR 1.50,95%CI1.36-1.64).Compared with the lowest tertile,those with the highest TyG tertile had a 2.05 times risk of Met S(HR 2.05,95%CI 1.73-2.43).Moreover,a non-linear relationship was detected between TyG index and Met S risk,and the inflection point of TyG index was 9.3.When TyG index≤9.3,a positive association was found between TyG index and risk of Met S(HR 1.99,95%CI1.73-2.28).When TyG index>9.3,no significant association was observed between them(HR 1.04,95%CI 0.88-1.22).Besides,ROC analysis showed that TyG index was better than waist circumference(WC),BMI,FPG,TG and serum uric acid(SUA)in diagnosing Met S.Summary:In this cohort study,an independent positive association was observed between TyG index and risk of Met S and a non-linear relationship was found between them,with a saturation threshold of 9.3 providing a more accurate basis for screening high-risk individuals.Besides,TyG index was superior to WC,BMI,TG,FPG and SUA in diagnosing Met S.Part Three Association between triglyceride-glucose index and risk of Metabolic dysfunction-associated fatty liver disease in the non-obese adults:a cohort studyObjective:Metabolic dysfunction-associated fatty liver disease(MAFLD),evolved from non-alcoholic fatty liver disease(NAFLD),is a new definition of fatty liver proposed by a panel of international experts in 2020,which emphasizes the key role of metabolic abnormalities in fatty liver.However,there is a lack of epidemiological studies on the prevalence of MAFLD.Both MAFLD and NAFLD are closely associated with obesity.However,the prevalence of NAFLD in non-obese people varied from 3 to30%in different ethnic groups.In addition,no significant differences in liver inflammation or fibrosis were found between non-obese NAFLD and obese NAFLD.Therefore,the prevalence of NAFLD in non-obese people and its risks may be significantly underestimated.IR remains the main pathophysiological basis of MAFLD.In recent years,TyG index as a simple substitute for IR has been confirmed to be associated with the risk of a variety of metabolic diseases.However,evidence for the relationship of TyG index with risk of MAFLD is currently blank.Therefore,this study aimed to explore the association between baseline TyG index and risk of MAFLD in non-obese adults.Methods:This study was a retrospective cohort study using professional bus drivers who underwent two health checks in a health examination center of Hebei General Hospital in 2017 and 2020,respectively.A total of 3502non-obese adults aged≥20 years were included,of whom 61.31%were males,with an average age of 37.05±7.65 years.The standardized questionnaire,physical examination form and biochemical index form were used to collect demographic,clinical disease information and blood biochemical indexes.The diagnosis of MAFLD was based on an international expert consensus statement.The Cox proportion-hazard model was used to investigate the association of TyG index with risk of MAFLD.Generalized additive models were used to identify non-linear relationships between TyG index and risk of MAFLD.If a non-linear association was observed,a two-piecewise linear regression model was performed to calculate the threshold effect of the TyG index on incident of MAFLD in terms of the smoothing plot.ROC curve analysis was conducted to estimate the predictive power of TyG index and other risk factors for MAFLD.Results:During 3 years of follow-up,408 of 3502 subjects aged≥20years developed MAFLD.Multiple regression analysis showed that there was a gender difference between TyG index and MAFLD.After adjusting for potential confounders,TyG index was positively associated with risk of MAFLD only in men(HR 1.59,95%CI 1.19-2.12),but not in women(HR1.06,95%CI 0.56-2.02).Besides,a non-linear relationship was detected between TyG index and risk of MAFLD in men,and the inflection point of TyG index was 8.64.When TyG index≤8.64,a positive association was found between TyG index and risk of MAFLD(HR 1.99,95%CI 1.24-3.18).When TyG index>8.64,no significant correlation was observed between them(HR1.28,95%CI 0.81-2.03).ROC curve showed that TyG index was better than WC,BMI,TG,FPG and SUA in diagnosing MAFLD.Summary:In this cohort study,TyG index was positively associated with risk of MAFLD in non-obese male subjects,and a non-linear relationship was found between them,with a saturation threshold of 8.64 providing a more accurate basis for screening high-risk individuals.TyG index was superior to WC,BMI,TG,FPG and SUA in diagnosing MAFLDPart Four Association between triglyceride-glucose index and Metabolic dysfunction-associated fatty liver disease in Chinese adults with Type 2 diabetes:a cross-sectional studyObjective:Metabolic dysfunction-associated fatty liver disease(MAFLD),derived from NAFLD,is a new definition of fatty liver proposed by an international expert group.There is an intricate and bidirectional relationship between Type 2 Diabetes(T2DM)and MAFLD,and IR is its common pathophysiological basis.Recent studies have demonstrated that TyG index is a reliable and simple proxy for IR and is associated with the risk of a variety of metabolic diseases.However,few studies focused on the association between TyG index and MAFLD,especially in patients with T2DM.Therefore,this study aimed to investigate the prevalence of MAFLD in T2DM patients,further studied the association between TyG index and MAFLD in T2DM patients,and explored the role of BMI in the relationship of TyG index with MAFLD.Methods:Data were consecutively obtained regarding 1355 patients with T2DM who visited the department of Endocrinology,Hebei General Hospital from January 2019 to December 2019.The standardized questionnaire,physical examination form and biochemical index form were used to collect demographic,clinical disease information and blood biochemical indexes.Spearman correlation analysis was used to explore the association between TyG index and MAFLD risk factors.Multivariate logistic regression analysis was used to explore the association of TyG index with MAFLD.Subgroup analysis was performed according to BMI group to assess the effect of BMI on the relationship of TyG index with MAFLD.Mediation analysis was used to explore whether BMI mediated the relationship between TyG index and MAFLD.Results:In this study,the prevalence of MAFLD in T2DM patients was51.88%.Compared with the non-MAFLD group,T2DM patients with MAFLD were relatively younger,had shorter duration of diabetes,and had higher levels of BMI,FPG,SUA,TG,low-density lipoprotein and TyG index.After adjusting for multiple confounders,we found a positive association between TyG index and MAFLD(OR 1.35,95%CI 1.09-1.67).When grouped by BMI,TyG index was positively associated with MAFLD only in patients with BMI≥23kg/m~2(OR 1.37,95%CI 1.09-1.71)rather than those with BMI<23 kg/m~2(OR 1.19,95%CI 0.59-2.41).Further mediating analysis showed that BMI partially mediated the indirect effect of TyG index on MAFLD.Summary:In this cross-sectional study,the prevalence of MAFLD in T2DM patients was 51.88%.TyG index was positively associated with MAFLD only in patients with BMI≥23kg/m~2,and BMI partially mediated the positive association of TyG index with MAFLD.Conclusion:1.TyG index is an easily measurable,low-cost,and intervenable surrogate for IR.We used two large cohort studies to confirm the independent positive association between TyG index and risk of diabetes,Met S and MAFLD.2.The non-linear relationships were found between TyG index and diabetes,Met S and MAFLD,and saturation threshold provides a more accurate basis for screening high-risk individuals.3.TyG index was superior to WC,BMI,TG,FPG and SUA in diagnosing and Met S and MAFLD.4.TyG index was positively associated with MAFLD in T2DM patients with BMI≥23kg/m~2,and BMI partially mediated the association of TyG index with MAFLD.