The Influence Of Glucose Excursion On Vascular Endothelial Function And Intervention Study In Elderly Type 2 Diabetic Patients

In the 21th century,diabetes mellitus and its complication has became a big public health problem of the world The recent study indicate that the Complication of diabetes mellitus was not only correlated with the whole level of blood glucose but also with the excess excursion of blood glucose.Studies in vitro have indicated that excess excursion of the blood glucose can accelerate apoptosis in endothelial cells.Its mechanism maybe related to oxidative stress.In the past,the means of monitoring glucose were mainly reflect "dot blood glucose" which had great limitation to evaluate the whole glucose excursion of the day. Continuous glucose monitoring system can offers us a better technique to monitor glucose excursion.Purpose of the current study is to find out that 1,the status of glucose excursion in the elderly type 2 diabetic patients by continuous glucose monitoring system,2,the relationship between glucose excursion and the concentration of NO,ET and 8-iso-PGF_2α3,glucose excursion effects on the function of vascular endothelial cells.The research is divided into three parts.The first is the study of the veracity of the CGMS;The second is the status of the glucose excursion in well-controlled elderly type 2 diabetic patients.The third is the protective role on vascular endothelial after improving glucose excursion in the elderly type 2 diabetic patients.PARTⅠCorrelation between CGMSBG and SMBG in the different measure conditionsObjective To evaluate the correlation between the dynamic blood glucose value (which monitored by CGMS)and the fast blood glucose value(picks the blood with the finger law)which corresponds,both under the different time interval and the different blood glucose level.Appraises the uniformities in two kinds of blood glucose values.Analyzes the accuracy of dynamic blood glucose values in different conditions. Methods One hundred and thirty type 2 diabetic patients in the Department of Gerontology Sixth People' s Hospital of Shanghai were enrolled and blood glucose were monitored with CGMS.Pearson correlation analysis was used to analyze CGMSBG and self monitoring blood glucose(SMBG)relevance separately in different survey time interval and different blood glucose level.Result①The correlation coefficient between CGMSBG values and paired SMBG values in the different age interval were as follows:the correlation coefficient r was 0.901 (P=0.0001),0.932(P=0.0001),0.875(P=0.0001),when the age was younger than 70,70～80and older than 80 years old respectively.②The correlation coefficient between CGMSBG values and paired SMBG values under the different blood glucose level were as follows:When the blood glucose value was below 4.4 mmol/L,the correlation coefficient r was 0.286(P=0.025).When it was between 4.4 and 10 mmol/L,the correlation coefficient r was 0.825(P=0.0001).When it was above 10 mmol/L,the correlation coefficient r was 0.838(P=0.0001).③In 1～6h,6～12h,12～24h,24～48h,48～72h after the installation of CGMS,The correlation coefficient r of CGMSBG values and SMBG values was 0.802,0.904,0.954,0.949 and0.926 respectively(all P=0.0001).Conclusions①The correlation between SMBG values and CGMSBG values are not associated with age.②The correlation between SMBG values and CGMSBG values was well In different level of blood glucose and different measuring phase.PARTⅡThe status of the glucose excursion in HbA_1c well-controlled elderly type 2 diabetic patientsObjective To study the status of the glucose excursion in HbA_1cwell-controlled elderly type 2 diabetic patients by continuous glucose monitoring system(CGMS)and to research the relation between hemoglobin A_1c(HbA_1c)and glucose excursion; Methods One hundred patients with type 2 diabetes(HbA_1c＜7.5%)were observed by CGMS for 3 days.Mean blood glucose,duration of hyperglycemia and mean amplitude of glucose excursions(MAGE)were analyzed by CGMS datas.Results①The percentage of the patients whose peak blood glucose over than 11.1mmol/L was 59.5%,the percentage of the patients whose vale blood glucose lower than 3.3mmol/L was 29.7%;②The percentage of blood glucose remained in the hyperglycemic range(≥7.8mmol/L)was 33%of the whole day,above 11.1mmol/L was 10.2%.and hypoglycemic range was 5.2%of the whole day;③HbA_1c,though associated with the mean blood glucose(r=0.55 P=0.004)and duration of hyperglycemia(r=0.48 P=0.001), failed to correlate with MAGE(r=0.12 P=0.55)and peak value of postprandial glucose(r=0.11,P=0.41).Conclusions In HbA_1cwell-controlled elderly type 2 diabetic patients,the glucose control is not very satisfactory in glucose excursion, HbA_1ccorrelates with chronic hyperglycemia but not with glucose excursion.CGMS provide information about the glucose excursion and trends in details,it can be used to evaluate the quality of glucose control in type 2 diabetic patients.PARTⅢThe effect of improving glucose excursion on vascular endothelial function in the elderly type 2 diabetic patientsObjective To investigate the effect of improving glucose excursion on vascular endothelial function in the elderly type 2 diabetic patients by continuous glucose monitoring system.Methods Fifty five elderly type 2 diabetic patients(male 32, female 23)were recruited.Specimens of blood were collected from elbow vein after 12h overnight fast to detect biochemical index and NO,ET,8-iso-PGF_2αand so on. In the same day,the patients were submitted to CGMS for three days.According to the result of CGMS monitoring,the patients were divided into two groups(high glucose excursion group:3×SDBG＞MBG and low glucose excursion group:3×SDBG＜MBG).In high glucose excursion group(male 17,female13),the therapy were adjusted for 4 weeks based on the CGMS monitoring.The aim of the treatment was to keep the fasting blood glucose in 4.4～6.1mmol/L,while in other conditions 4.4～8.0mmol/L.After the treatments,the specimens of blood were collected again to detect the related index.Results(1)The concentration of NO of high glucose excursion group were lower than that of low glucose excursion group(39.64±9.09 vs 63.36±5.12 umol/L,P=0.0001),while the concentration of the 8-iso-PGF2_αand the ET of high glucose excursion group were higher than that of low glucose excursion group (57.56±3.86 vs 34.21±3.82 pg/ml,P=0.0015),(117.18±45.03 vs 72.01±25.21 pg/ml,P=0.0001).(2)In high glucose excursion group,the index of glucose excursion such as SDBG(2.53±0.87mmol/L),LAGE(11.42±2.89 mmol/L)and MAGE(5.57±2.13 mmol/L)before treatment were decreased to SDBG(1.48±0.46 mmol/L),LAGE(7.41±2.09 mmol/L)and MAGE(3.34±1.14 mmol/L)after treatment(P=0.0001,0.0000 and 0.0004 respectively).(3)In high glucose excursion group,plasma concentration of NO in diabetic patients before treatment was(39.64±9.09)umol/L,which increased significantly after 4 weeks treatment(59.48±6.32) umol/L(P=0.0141).ET before treatment was(117.18±45.03)pg/ml,which decreased after treatment(90.01±28.95)pg/ml(P=0.0384).8-iso-PGF_2αbefore treatment was (57.56±3.86)umol/L,which decreased after 4 weeks treatment(43.27±3.72) umol/L(P=0.0013).(4)In high glucose excursion group,stepwise regression analysis demonstrated that the change of NO were predicted by the change of SDBG and LAGE(β=-15.065,-0.252,P=0.001,0.083),the change of ET was predicted by the change of LAGE(β=5.156,P=0.011),while the change of 8-iso-PGF_2αwas predicted by the change of SDBG(β=1.959,P=0.013).Conclusions By CGMS monitoring,the improvement of glucose excursion in the elderly type 2 diabetic patients can ameliorate the damage to the vascular endothelial function significantly.