An Analysis About The Changes Of Telomere Length In Patients With Type 2 Diabetes Mellitus And The Relationship Between Telomere Length With Major Adverse Cardiac Events

Aims: Telomere length and telomere shortening rate are accepted indicators of aging in cross-sectional population studies.This study aimed to investigate the effects of various antidiabetic agents on telomere length in patients with type 2 diabetes.Methods: Leukocyte telomere length was measured by terminal restriction fragment analysis,and the telomere shortening rate(TSR)was calculated in 388 patients with type 2diabetes.The telomere length and TSR were compared in the following groups:(1)type 2diabetes patients with or without antidiabetic treatment;(2)type 2 diabetes patients treated with different antidiabetic agents;(3)type 2 diabetes patients treated with acarbose or receiving no treatment.Results: First,type 2 diabetes patients treated with antidiabetic agents showed better glycemic control than patients not receiving any antidiabetic agents,as well as more modest TSR(treatment group vs.non-treatment group:-14.01 ± 3.28 vs.-15.74 ± 6.21,P < 0.0001).Second,the TSR of patients in different antidiabetic drug treatment groups differed from each other.Interestingly,the TSR of type 2 diabetes patients treated with acarbose was significantly higher than that of patients receiving antidiabetics not containing acarbose(acarbose-free group vs.acarbose group:-9.29 ± 4.30 bp/years vs.-22.14 ± 4.65 bp/years,P< 0.0001),although glycemic control did not significantly differ between these groups.Third,to confirm the side effects of acarbose independent of glycemic control,type 2diabetes patients treated with acarbose and those without any treatment were compared.The acarbose group showed better glycemic control but a higher TSR(acarbose group vs.nontreatment group-22.14 ± 4.66 bp/years vs-15.74 ± 6.21 bp/years,P < 0.0001).Conclusions: Antidiabetic treatments,except for acarbose treatment,slow telomere shortening.By contrast,acarbose accelerates telomere shortening in patients with type 2diabetes independent of glycemic control.Aims: Telomere length has been accepted an indicator of cardiovascular disease in cross-sectional studies.The aim of this study was to examine the potential association of shorten telomere length with macrovascular complications and major adverse cardiac events(MACE)in type 2 diabetes mellitus(T2DM).Methods: This cross-sectional study was carried out on 554 type 2 diabetic patients.Based on the complications,those patients were divided into three groups: T2 DM without macrovascular complications group(Control),T2 DM with macrovascular complications but without MACE group(NON-MACE)and T2 DM with MACE group(MACE).Characteristics were determined using standard laboratory techniques,and leukocyte telomere length,the levels of serum high sensitive C-reaction protein(hs CRP)and plasma HCY were measured.Results:The length of telomere was shortest in MACE group,and it was shorter in NON-MACE than control group.The levels of hs CRP and HCY were showed significantly increased in MACE group than in other two groups(P<0.0001),whereas there were almost no changes between NON-MACE and control in these two biomarkers for cardio-cerebrovascular diseases(P>0.05).Regression analysis data indicated that shorten telomere length,increasing level of hs CRP and HCY were all independent risk factors for development of NON-MACE and MACE(all P<0.05).Moreover,in NON-MACE,the ROC plot indicated an area under the curve for telomere length,hs CRP and HCY was0.750(95%CI 0.698-0.801),0.561(95%CI 0.501-0.621)and 0.563(95%CI 0.503-0.623),respectively.The AUC of telomere length was significantly higher compared with hs CRP and HCY.In MACE,an area under the curve(AUC)of telomere length,hs CRP and HCY was 0.845(95%CI 0.803-0.886),0.729(95%CI 0.678-0.779)and 0.758(95%CI0.709-0.808),respectively.The AUC of telomere length was greater significant difference than that of hs CRP and HCY alone(all P<0.05).The combination of telomere length,hs CRP and HCY showed best capability of predicting MACE.Remarkably,the telomere length could serve as an assistant marker in diagnosing macrovascular complications,with6263.2bp for predicting NON-MACE and 6154.0bp for MACE.Conclusion:Our findings indicated a novel role of short telomere length in the various stages of diabetic macrovascular complications.The combination of hs CRP,HCY and telomere length showed best capability of predicting MACE,in which telomere plays a critical role.