Significance Of Changes Of CD69,TGF-?1 And S1P In Patients With Type 2 Diabetes Mellitus Complicated With Diabetic Kidney Disease

Objective:Diabetic kidney disease(DKD)is one of the common microvascular complications of diabetes.Its pathogenesis is complex,involving various factors such as hemodynamic changes,oxidative stress and activation of the renin-angiotensin system.Recent studies have gradually revealed that immune system disorders are closely related to the occurrence of type 2 diabetes and diabetic kidney disease.Among them,various inflammatory mediators constitute the cytokine network of DKD.As a core factor,TGF-?1 is involved almost entirely.The development of DKD includes the metabolism of mesangial matrix(ECM)and the proliferation,hypertrophy and apoptosis of renal cells.In recent years,it has been found that the regulatory factor S1 P of T lymphocytes and the signal transduction molecule CD69 are also closely related to the occurrence of DKD.In this study,we compared the serum levels of S1 P,TGF-?1 and CD69 in patients with type 2 diabetes mellitus with different levels of urinary albumin-to-creatinine ratio to discuss the relationship between urinary albumin-to-creatinine ratio levels with S1 P,TGF-?1 and CD69.To explore the pathogenesis of diabetic kidney disease by S1 P,TGF-?1 and CD69,and provide new ideas for the clinical treatment of diabetic kidney disease.Methods:Eighty-eight patients with type 2 diabetes who were admitted to the Department of Endocrinology,the First Hospital of Shanxi Medical University from January 2018 to October 2018 were selected to meet the diagnostic criteria for diabetes(WHO,1999).There were 45 males and 43 females with an average age of(59.53±5.90)years old.All subjects excluded acute diabetes complications,acute infectious diseases,primary aldosteronism,steroid and nephrotoxic drugs,malignant tumors,malignant hypertension,primary kidney disease,and others with abnormal liver and kidney function.According to the urinary albumin-to-creatinine ratio,the patients were divided into no nephropathy group,early nephropathy group and clinical nephropathy group,including 37 cases without nephropathy(17 males and 17 females)and 31 patients with early nephropathy(male 15).There were 16 female patients in the clinical nephropathy group(10 males and 10 females).There were no statistical differences in the baseline data of the general conditions of gender,age,body mass index,and blood pressure in the three groups.All investigators measured serum sphingosine-1,transforming growth factor-?1 and peripheral blood T lymphocyte CD69 antigen expression,including blood cell analysis,urinary albumin-to-creatinine ratio,various blood glucose,blood lipid indicators and body weight.Biochemical testing and clinical information,and related statistical analysis of the above indicators.Results:1.There were no statistically significant differences between the three groups in terms of age,BMI,duration of disease,diastolic blood pressure,triglycerides,high-density lipoprotein,monocyte values,and lymphocyte values.2.The systolic blood pressure,TC,LDL,Cr,WBC,NEU,NLR and eGFR in the clinical nephropathy group were significantly higher than those in the non-nephrotic group and the early nephropathy group.The FPG,eGFR and HbA1 c in the early nephropathy group were significantly higher than those in the non-nephrotic group.3.Comparison of cytokine levels: CD69 in clinical nephropathy group was significantly higher than that in non-nephrotic group.The level of S1 P in the clinical nephropathy group and the early renal disease group were significantly lower than that in the non-nephrotic group.There was no significant difference in TGF-?1 level among the three groups.4.Correlation analysis of factors affecting CD69 showed that CD69 was positively correlated with systolic blood pressure,FPG and TC,and had no correlation with TGF-?1and S1 P.Conclusion:The increased expression of CD69 in peripheral blood of type 2 diabetic patients and the decrease of serum S1 P level may be the key factors in the occurrence and development of DKD.Serum CD69 levels were positively correlated with fasting blood glucose and cholesterol levels in type 2 diabetic patients,suggesting that glucose and lipid metabolism disorder is one of the important causes of inflammation-promoting environment in diabeticpatients.