Analysis Of Blood Glucose Fluctuation In Type 2 Diabetic Nephropathy And Its Clinical Significance

Objective1.Analyze the blood glucose fluctuations of type 2 diabetes(T2DM)patients with CKD,and analyze its clinical value.2.Establish a sensitive,mature and reliable blood glucose fluctuation model for type 2diabetic mice to further clarify the factors of blood glucose fluctuation on diabetic nephropathy(DN)and provide a certain experimental basis for clinical practice.Method1.483 T2 DM patients in the endocrinology department of Eastern Theater General Hospital from July 2017 to September 2018 were selected,all of whom comply with the T2 DM diagnostic criteria of "Chinese Type 2 Diabetes Prevention and Treatment Guidelines(2013 Edition)".We apply dynamic blood glucose monitoring system to continuous blood glucose monitoring for 72 hours,and collect blood glucose fluctuation indicators,including standard deviation of blood glucose level(SDBG),mean absolute difference of blood glucose(MODD)and average blood glucose fluctuation range(MAGE).We collect the basic information of patients such as age,sex,course of disease and biochemical indicators such as glycated hemoglobin(Hb Alc),liver function and kidney function.According to the diagnostic criteria of CKD,it was divided into type 2 diabetes without CKD group(NCKD group,165cases)and type 2 diabetes with CKD group(CKD group,318 cases),.And according to the DN diagnostic,the latter group is divided to the diabetic nephropathy group (DN group,PDN≥0.5,151 cases)and non-diabetic nephropathy group(NDRD group,PDN <0.5,167 cases),the general situation and the difference in blood glucose fluctuation between the groups were analyzed,and we use multi-factor logistics regression tp analysis the influencing factors of DN.2.Intraperitoneal injection of streptozotocin(STZ)combined with high-fat diet feeding was used to establish 11 mouse models of type 2 diabetes(T2DM).Seven of them were randomly selected as type 2 diabetes blood glucose fluctuation group(T2DM FDM group,n = 7)and given intraperitoneal injections of glucose and insulin at different times for 7 consecutive weeks.Tthe remaining was type 2 diabetes persistent hyperglycemia group(T2DM group,n = 4),and control group was set(Con group,n = 7).The weight of the mice was measured every week.After 7 weeks,we monitored whole-day blood glucose of each group of mice with a blood glucose meter,calculated the blood glucose standard deviation(SD),largest amplitude of glycemic excursions(LAGE)and coefficient of variation(CV)of the blood glucose fluctuation index.and obtained the urine of mice with a metabolic cage.The urinary albumin and creatinine values of mice were measured by ELISA,and the albumin /creatinine ratio of mice was calculated,and then the mice were sacrificed the next day.Comparing the blood glucose fluctuation and renal function changes of mice in each group,to explore the influence of blood glucose fluctuation on urine protein of T2 DM mice.Results Analysis of blood glucose fluctuation in type 2 diabetes patients with CKD(1)Comparison of clinical data between CKD group and NCKD group There was no significant difference in age,gender,diastolic blood pressure and AST between the two groups(P> 0.05).The systolic blood pressure,duration of diabetes,BMI,creatinine,uric acid,cholesterol,triglyceride,urine microalbumin / creatinine ratio,24 h urine protein levels of CKD group were significantly higher than NCKD group.Hb,plasma albumin,ALT,total bilirubin,Indirect bilirubin,direct bilirubin,e GFR levels of CKD group were lower than the NCKD group,the difference was statistically significant(P <0.01 or P <0.05).(2)Comparison of clinical data between NDRD group and DN group There was no significant difference in gender,diastolic blood pressure,BMI,uric acid,cholesterol,triglyceride between the two groups(P>0.05).Age,systolic blood pressure,duration of diabetes,creatinine,urine microalbumin / creatinine ratio,24 h urine protein levels of DN group were significantly higher than NDRD group.Hb,albumin,AST,ALT,total bilirubin,indirect bilirubin,direct The levels of bilirubin and e GFR of DN group were lower than those of the NDRD group,and the differences were statistically significant(P <0.01 or P <0.05).(3)Comparison of blood glucose levels of the three groups There was no statistically significant difference in Hb A1 c among the three groups(P>0.05).And there were significantly differences in blood glucose fluctuations SDBG,MODD,and MAGE(P <0.01).The blood glucose fluctuations SDBG,MODD and MAGE in DN group were significantly higher than those in NDRD group and NCKD group(P <0.01 or P <0.05).(4)Analysis of influencing factors of DN group For patients in the NCKD and DN groups,binary multivariate logistic regression analysis was performed.Duration of diabetes,systolic blood pressure and blood glucose fluctuation were independent risk factors for DN [ duration of diabetes:OR=1.1.012,95%CI(1.007 ~ 1.016);:systolic blood pressure OR=1.036,95%CI(1.016~1.055);MAGE:OR=1.228,95%CI(1.024~1.474)](P <0.01 or P <0.05).The effect of blood sugar fluctuations on urine protein in type 2 diabetic mice(1)General characteristics of three groups of mice Mice in T2 DM group and T2 DM FDM group had poor mental state,unresponsiveness,decreased activity,tarnishing,hair loss and polydipsia,polyuria and polyphagia.(2)Comparison of body weight of three groups of mice The body weight of the Con group showed an upward trend,while the body weight of the T2 DM group and T2 DM FDM group showed a downward trend.(3)Comparison of blood glucose fluctuation levels of three groups of mice T2 DM FDM group’s blood glucose fluctuation was significantly higher than T2DM group and Con group,the difference was statistically significant(P <0.01 or P <0.05).(4)Comparison of urine protein levels in three groups of mice The urine albumin / creatinine ratio of T2 DM FDM group was significantly higher than that of T2 DM group and Con group,and the difference was statistically significant(P <0.01 or P <0.05).Conclusion1.There is a statistical difference between the DN group,the NDRD group and the NCKD group.The blood glucose fluctuation is an independent risk factor for DN.2.Glucose fluctuation promotes the increase of urine protein level in diabetic mice.of...