| ObjectiveTsukushi（TSK）is a liver-derived secreted protein,consisting of 353 amino acids.Recent researches showed that obesity and excessive energy expenditure promote the expression and secretion of TSK in liver.Additionally,Deletion of TSK would increase thermogenesis,energy expenditure and improve insulin sensitivity,suggesting TSK may be a promising target for predicting and treating obesity,type 2diabetes mellitus（T2DM）and other metabolic diseases.This study measured serum TSK levels for the first time in new-diagnosed T2DM patients and explored the correlations between circulating TSK levels and glucose and lipid profile.MethodsA total of 172 subjects were enrolled into this study,including 86newly-diagnosed T2DM patients who were adimitted into department of endocrinology between September 2017 and November 2020,and 86 sex-,age-matched normal control volunteers.All participants were measured anthropometric indices including heigth,weight,waist circumference,hip circumference and blood pressure with uniform standards.We analyzed the concentrations of TSK by ELISA in serum of 172 subjects in whom 75g oral glucose tolerance test was performed,glusose,insulin levels,c-peptide,glycosylated hemoglobin（Hb A1c）,liver enzymes and lipid profile were measured.Results（1）Compared with normal glucose tolerance group（NGT）,T2DM patients showed higher body mass index（BMI）,waist circumference（WC）,waist-to-height ratio（WHt R）,systolic blood pressure（SBP）,diastolic blood pressure（DBP）,fast plasma glucose（FPG）,2h plasma glucose（2h PG）,fast insulin（FIns）,fast c-peptide（FC-P）,Hb A1c,triglycerides（TG）,alanine aminotransferase（ALT）,aspartate aminotransferase（AST）,g-glutamyl transpeptidas（GGT）and homeostasis model assessment of insulin resistance（HOMA-IR）and lower high-density lipoprotein cholesterol（HDL-C）,homeostasis model assessment ofβcell（HOMA-β）,ISI,MCR（P<0.05）.（2）Compared with NGT group,Serum TSK levels were significantly higher in T2DM patients（P<0.001）.（3）All individuals were divided into three groups according serum TSK concentrations tertiles:T1 group（TSK≤0.74ng/ml,n=57）,T2 group（0.74ng/ml<TSK<1.33ng/ml,n=58）,T3 group（TSK≥1.34ng/ml,n=57）.Incidence of T2DM in T2 group and T3 group were significantly higher than that in T1 group.BMI,WHt R,SBP,2h PG,Hb A1c,GGT,HOMA-IR showed an increasing trend across TSK tertiles.Meanwhile,Levels of HOMA-βand MCR decreased gradually.（4）Partial correlation analysis showed that serum levels of TSK were positively correlated with BMI、WC、Wht R、SBP、DBP、FPG、2h PG、FIns、FC-P、Hb A1c、TC、LDL-C、ALT、GGT、HOMA-IR and negatively correlated with HOMA-βand MCR.This statistically significant association still remianed between serum TSK and FPG,2h PG,Hb A1c,TC after adjustment for age,gender and BMI.（5）Multiple stepwise regression analysis was performed with BMI,FPG,2h PG,Hb A1c,TC,HOMA-β,MCRstumvollas independent variables and serum TSK as dependent variable.The results showed that BMI,2h PG,TC were independently related factors influcing serum TSK levels（R2=0.146,P<0.001）.（6）We performed a binary logistic regression analysis in which the presence of T2DM was designated as the dependent variable and serum TSK levels as independent variable（model 1）.In comparison with the T1 group,T2,T3 group was associated with higher risk of T2DM.In the model 2 additionally adjusting for age gender,BMI,SBP,DBP,smoking status,alcohol drinking and history of hypertension,compared with T1 group,T2,T3 group was also associated with higher risk of T2DM.Finally,in the fully adjusted multivariable model（model3）,compared with T1 group,the ORs value for incident T2DM in T2 and T3 group were 5.797（1.822～18.442）and8.914（2.563～31.010）（P<0.01）.Conclusions（1）Serum TSK levels was significantly increased in new-diagnosed T2DM patients and show significant correlation with glucose and lipid metabolism.（2）Incidence of T2DM increased with increasement of serum TSK levels.（3）Serum TSK levels was risk factor for T2DM and played an important role in occurrence and development of T2DM. |
