A Study On The Correlation Between Serum SIRT1,GDF11 And Mild Cognitive Impairment In Type 2 Diabetes Mellitus

ObjectiveThe study aims to explore the correlation between the level of serum silent information regulator 1(SIRT1),the growth differentiation factor 11(GDF11)and mild cognitive impairment(MCI)in the patients with type 2 diabetes mellitus(T2DM)and to evaluate their significance of diagnosis in the patients suffered from T2 DM complicated by MCI.MethodsThe study recruited 211 patients who were hospitalized in the Endocrinology Department of Taizhou People’s Hospital while 39 patients were excluded due to not meeting the enrollment and exclusion criteria and experimental grouping criteria,and finally 172 patients were included in this study.General information and related clinical laboratory indicators were collected from these patients including gender,age,duration of diabetes,years of education,height,weight,fasting blood glucose(FBG),glycated hemoglobin(Hb A1c),fasting C-peptide(FC-P),fasting insulin(FINS),β2 microglobulin(β2MG),uric acid(UA),serum creatinine(Scr),urinary albumin to creatinine ratio(ACR),Cystain C(Cys-C),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),total cholesterol(TC),triglyceride(TG),apolipoprotein E(Apo E),white blood cell(WBC),C-reactive protein(CRP).And then body mass index(BMI),homeostasis model assessment insulin resistance(HOMA-IR)and homeostasis model assessment of β-cell function(HOMA-β)were recorded after calculation.The enzyme-linked Immunosorbent Assay(ELISA)was used to detect the level of SIRT1 and GDF11 in the serum after collecting the fasting venous serum samples of all subjects and extracting the upper serum.The subjects were divided into two groups according to the score of Montreal Cognitive Assessment(Mo CA)and Mini-mental State Examination(MMSE)which were used to evaluate the cognitive function.One group consisted of 100 patients who suffered from T2 DM without MCI(T2DM-NCI group:19≤Mo CA score≤25and 25≤MMSE Score≤26),and 72 patients who suffered from T2 DM with MCI(T2DMMCI group: Mo CA score≥26 and MMSE score≥27)were included in the other group.The recorded data was analyzed between two groups by statistics.And the correlation between the level of the SIRT1 or GDF11 in the serum and MCI in T2 DM was evaluated besides the clinical features.Furthermore,the values of the SIRT1 and GDF11 of serum to diagnose MCI in T2 DM patients was predicted.Result1.In this study,none significant differences were found in gender,LDL-C,BMI,Hb A1 c,FBG,β2MG,UA,Scr,ACR,TC,TG,Apo E,WBC,CRP,FINS and HOMA-βbetween T2DM-NCI group and T2DM-MCI group statistically(P>0.05).The differences in years of education,duration of diabetes,age,FC-P,Cys-C,HDL-C,HOMA-IR between the two groups were statistically significant(P<0.05).2.Strong evidence showed that the serum levels of SIRT1 and GDF11 in two groups were statistically different(P<0.001).The serum level of SIRT1 was lower in T2 DMMCI group than that in T2DM-NCI group but the serum level of GDF11 was higher in T2DM-MCI group than that in T2DM-NCI group.3.Spearman correlation showed that serum SIRT1 level has a negative correlation with Cys-C(r=-0.232,P=0.002)and TC(r=-0.150,P=0.049)and was positively correlated with years of education(r=0.185,P=0.015).Serum GDF11 level was negatively correlated with years of education(r=-0.223,P=0.003)and was positively correlated with HOMA-IR(r=0.150,P=0.049).There was no correlation between serum SIRT1 and serum GDF11 in the statistic(r=-0.009,P=0.912).4.Binary variable logistic regression analysis showed that the higher SIRT1 levels(OR=0.989,P<0.001)and longer years of education(OR=0.796,P=0.006)were negatively correlated with T2 DM complicated by MCI,which were independent protection of T2 DM cognitive Factors.While advanced age(OR=1.064,P=0.038),the higher level of GDF11(OR=1.057,P<0.001)and higher HOMA-IR(OR=3.336,P=0.010)were positively correlated with T2 DM complicated by MCI,which were independent risk factors of MCI in T2 DM.5.Using ROC curve analysis to compare the diagnostic values of SIRT1 and GDF11 about MCI in T2 DM,the diagnostic value of serum SIRT1 is higher(AUC=0.823,sensitivity =63.89%,specificity =91.00%)and the cut-off value is 333.14 ng/L.While GDF11 has lower diagnostic value(AUC=0.700,sensitivity=61.11%,specificity=72.00%)with cut-off value 93.07 ng/L.Conclusion1.The years of education,age,serum SIRT1 level,serum GDF11 level and HOMA-IR are independent factors for T2 DM complicated by MCI.T2 DM patients who are elder and with lower education level,lower serum SIRT level,higher serum GDF11 level,higher HOMA-IR index may be more susceptible to MCI.2.Serum SIRT1 and GDF11 are meaningful to diagnose MCI in T2 DM.They may be one of the biological markers in predicting MCI in T2 DM patients.3.Compared with the serum GDF11,serum SIRT1 has higher specificity in predicting MCI in T2 DM patients.