Correlation And Mediation Analysis Between GGT/HDL-C And Visceral Obesity In Type 2 Diabetes Mellitus

ObjectiveType 2 diabetes mellitus（T2DM）is an abnormal glucose metabolism disease whose prevalence increases with the prevalence of obesity,which is an independent risk factor for T2DM.In recent years,visceral obesity（VO）has been found to be closely related to a variety of metabolic diseases.Visceral adipose tissue（VAT）can secrete free fatty acids leading to impaired pancreatic beta cell function and insulin resistance（IR）.Studies have shown that visceral fat area（VFA）is an indicator of abdominal obesity and is related to insulin sensitivity.Gamma-glutamyl transferase to high-density lipoprotein cholesterol ratio（GGT/HDL-C）is a novel metabolic indicator.Elevated GGT/HDL-C levels are associated with various diseases such as T2DM and metabolic associated fatty liver disease（MAFLD）.However,the correlation between GGT/HDL-C and visceral fat in T2DM patients has not been studied.Therefore,this study was conducted to analyze the correlation between GGT/HDL-C and VFA in T2DM patients to provide a simple and feasible evaluation index for the early screening of VO.To explore the pathway of GGT/HDL-C on VO in T2DM patients,GGT/HDL-C as independent variable,VO as dependent variable,body measurement indicators,smoking and drinking history as mediating variables,explore the mediating role of mediating variables between GGT/HDL-C and VO,which can provide effective intervention indicators for T2DM with VO in clinic.MethodsA total of 1772 patients with T2DM who attended to the National Standardized Metabolic Management Center（MMC）in the Affiliated Hospital of Jiangsu University from June 2018 to September 2021 were enrolled in this study.General clinical data such as age,gender,smoking and drinking were collected.Body measurement indicators such as height,weight,waist circumference（WC）and hip circumference（HC）were measured,and body mass index（BMI）and waist hip ratio（WHR）were calculated.After fasting for more than 8 hours at night,fasting cubital venous blood was collected the next morning,and relevant biochemical indexes such as liver and kidney function and blood lipids were measured,and oral glucose tolerance test（OGTT）was performed.The VFA and subcutaneous fat area（SFA）were measured by dual bioelectrical impedance,and VFA/SFA ratio（V/S）was calculated.All patients were divided according to GGT/HDL-C quartiles.The differences of basic clinical data,body measurement indicators,glucose metabolism indicators such as fasting plasma glucose（FPG）and fasting insulin（FINS）,biochemical indicators such as liver and kidney function,blood lipids and the incidence of VO were compared.The correlation between GGT/HDL-C and body measurement indicators,liver and kidney function and glycolipid metabolism indicators were analyzed.The patients were divided into VFA-L group（VFA<100cm²,n=1119）and VFA-H group（VO group,VFA≥100 cm²,n=653）according to the VFA,and the differences of GGT/HDL-C and other clinical indicators were compared.The correlation between GGT/HDL-C and other clinical indicators in VO group was analyzed.Receiver operating characteristic（ROC）curve was plotted to evaluate the predictive value of GGT/HDL-C for T2DM patients with VO.According to the correlation analysis results,a mediation model was constructed to explore the pathway of GGT/HDL-C on T2DM with VO.With GGT/HDL-C as independent variable,T2DM with VO as dependent variable,body measurements,history of smoking and drinking as mediating variables,SPSS software was used to test the mediating effect,and the proportion of mediation effect（indirect effect/total effect×100%）was calculated.Results1.All patients were divided into four groups according to GGT/HDL-C quartiles:Q1,Q2,Q3,and Q4,with group Q1（GGT/HDL-C<16.43）,group Q2（16.43≤GGT/HDL-C<25.96）,group Q3（25.96≤GGT/HDL-C<46.07）,and group Q4（GGT/HDL-C≥46.07）,and 443 cases in each group.The prevalence of VO was significantly higher in the high GGT/HDL-C group,with the prevalence of VO in the four groups was 18.96,32.51,44.24,and 51.69%,respectively（P<0.001）.GGT/HDL-C level was higher in VO group than in VFA-L group,which were34.02（21.86,57.42）and 22.22（14.52,38.95）,respectively（P<0.001）.2.Compared with group Q1,the proportions of males,smoking and drinking,the proportion of hyperlipidemia,the proportion of MAFLD,height,weight,BMI,neck circumference（NC）,WC,HC,WHR,VFA,SFA,V/S,systolic blood pressure（SBP）,diastolic blood pressure（DBP）,mean arterial pressure（MAP）,FPG,FINS,fasting C-peptide（FCP）,2hour postprandial plasma glucose（2h PG）,2 hour postprandial C-peptide（2h CP）,glycated hemoglobin A1c(Hb A_1c),homeostasis model assessment of insulin resistance（HOMA-IR）,homeostasis model assessment ofβ-cell function（HOMA-β）,alanine aminotransferase（ALT）,alkaline phosphatase（ALP）,aspartate aminotransferase（AST）,albumin（ALB）,triglyceride（TG）,total cholesterol（TC）,serum creatinine（Scr）and Uric acid（UA）in groups Q2,Q3 and Q4 were increased,while age and homeostasis model assessment of insulin sensitivity（HOMA-ISI）were decreased gradually.2 h postprandial insulin（2h INS）was only increased in the Q3 and Q4groups（P<0.05）.With the increase of GGT/HDL-C level,the proportions of smoking,the proportion of hyperlipidemia and VO,height,weight,BMI,NC,VFA,SFA,DBP,MAP,FINS,FCP,2h CP,HOMA-IR,ALT,AST,ALP,ALB,TG,and UA were gradually increased in the Q4group,while age and HOMA-ISI were decreased gradually（P<0.05）.3.Correlation analysis showed that GGT/HDL-C was positively associated with gender,history of smoking and drinking,the proportion of MAFLD and hyperlipidemia,DBP,height,weight,BMI,neck circumference（NC）,WC,WHR,VFA,DBP,FPG,FINS,FCP,2h PG,2h CP,HOMA-IR,ALT,AST,ALP,ALB,TG,UA and negatively associated with age and HOMA-ISI in the total population and T2DM patients with VO（P<0.05）.GGT/HDL-C was negatively correlated with low-density lipoprotein cholesterol（LDL-C）and blood urea nitrogen（BUN）only in T2DM patients with VO（P<0.05）.4.The ROC analysis showed that the area under the ROC curve of GGT/HDL-C for predicting the occurrence of VO in T2DM patients was 0.660（95%CI:0.637～0.682,P<0.001）,which had better predictive value than GGT or high-density lipoprotein cholesterol（HDL-C）（P<0.001）.The cut-off value of GGT/HDL-C was 22.99,with a sensitivity of 73.05%and a specificity of 52.19%.5.Based on GGT/HDL-C cut-off value,all patients were divided into high GGT/HDL-C group（>cutoff value,n=1010）and low GGT/HDL-C group（<cutoff value,n=762）,and the differences of clinical data and biochemical indicators were compared.Compared with low GGT/HDL-C group,the proportions of males,smoking and drinking,the proportion of MAFLD,hypertension,hyperlipidemia,VO and lipid-lowering drugs used,height,weight,BMI,NC,WC,hip circumference（HC）,WHR,SBP,DBP,MAP,VFA,SFA,V/S,FPG,FINS,FCP,2h PG,2h INS,2h CP,HOMA-IR,HOMA-β,ALT,AST,ALP,ALB,TG,TC,Scr and UA in high GGT/HDL-C group were increased,while age and HOMA-ISI were decreased（P<0.05）.The prevalence of VO in high GGT/HDL-C group was higher than that in low GGT/HDL-C group,which was 47.20 and 23.10%,respectively（P<0.001）.6.Mediation models were constructed based on the results of correlation analysis,with GGT/HDL-C as independent variable,T2DM with VO as dependent variable,and body measurement indicators,smoking and drinking history as mediating variables,and the mediating effects were tested using Model 4 of the process plug-in in SPSS software.There was a significant correlation between GGT/HDL-C and T2DM with VO,the total effect（OR=0.048,P<0.001）,and BMI,NC,HC,SFA,smoking,drinking,hyperlipidemia and MAFLD played a partial mediating role in GGT/HDL-C predicting VO,with the highest proportion of BMI mediator effect was 50.00%（OR=0.024,P<0.001）.ConclusionsGGT/HDL-C is a simple and easy indicator for early assessment of VO in T2DM.T2DM patients with higher GGT/HDL-C are at greater risk of VO.BMI,smoking and drinking all play a partial mediating role in GGT/HDL-C predicting VO.Therefore,in the examination of T2DM patients,more attention should be paid to GGT/HDL-C,BMI,smoking and drinking and providing lifestyle education to patients,which can play a role in the prevention of VO.