| Objective:With the aggravation of population aging and the change of people’s life style,the threat of NCDS to human health is increasing.In the past 40 years,the prevalence of diabetes in China has increased from 0.7%in 1980 to 10.4%in 2013,and diabetes has gradually become an epidemic chronic disease from a rare disease.The pathogenesis of diabetes and its complications is not yet complete,and it is currently believed that type 2diabetes and inflammatory response are mutually causal and closely related.Increased leukocyte count and its inflammatory phenotype in diabetes may play a key role in macrovascular and microvascular complications.The purpose of this study was to investigate whether blood glucose control reduces white blood cell count and inflammatory gene expression and possible mechanisms.Methods:A total of 63 patients(including type 1 and type 2 diabetes mellitus)with poor blood glucose control were collected from the Affiliated Provincial Hospital of Anhui Medical University and network hospital between January 2015 to December 2017,including 45males and 18 females,with an average age of(42.9±5.1)years.In the first stage,according to the patient’s blood glucose level and personal preference,the individual hypoglycemic program was determined by the specialist.The baseline data of diabetic patients were collected,including:gender,age,type of diabetes,diabetes history,body mass index(BMI),fasting glucose,HbA1c,merging,cardiocerebral diseases,medications(including diabetes medications)and laboratory data(including white blood cell count,neutrophil count,mononuclear cell count and lymphocyte count,total cholesterol,high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C)and triglycerides).The mRNA of inflammatory genes in peripheral blood granulocytes and monocytes were detected.The second stage was glucose-lowering treatment of 63 cases diabetic patients.The information of 63 patients with diabetes were collected again 3 months later,include:body mass index(BMI),fasting glucose,HbA1c,medications(including diabetes medications)and laboratory data(including white blood cell count,neutrophil count,mononuclear cell count and lymphocyte count,total cholesterol,high-density lipoprotein cholesterol(HDL-C),low density lipoprotein and triglyceride);mRNA of inflammatory genes in peripheral blood granulocytes and monocytes were detected.The decrease of HbA1c by more than 1.5%was defined as improvement,while the decrease of HbA1c by less than 1.5%was defined as unimprovement.The body mass index,fasting glucose,HbA1c,medications(including diabetes medications),laboratory data(including white blood cell count,neutrophil count,mononuclear cell count and lymphocyte count,total cholesterol,high-density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C)and triglycerides)and peripheral blood neutrophils and monocytes inflammatory gene mRNA expression of two groups were compared.Results:1.According to the decrease of HbA1c in patients with diabetes after 3 months of treatment,63 patients with diabetes at baseline were divided into the improved group(42 cases)and the unimproved group(21 cases).The average age,the sex ratio,proportion of type 1 and type 2 diabetes,proportions of newly diagnosed with diabetes,hypertension disease,proportion of cerebral infarction,proportion of coronary heart disease(CHD),BMI,total cholesterol,high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),triglycerides,diabetes main medications and other were no statistically significant difference between two groups(p>0.05).2.After 3 months of hypoglycemic treatment,fasting blood glucose,HbA1c,BMI,total cholesterol,and triglyceride in the improved group were 8.17±1.07 mol/L,6.78±0.87%,25.48±2.08 kg/m~2,7.00±1.56 mmol/L,4.17±0.94 mmol/L,and 2.77±1.44mmol/L,respectively.The differences were statistically significant(p<0.05).In the unimproved group,the total cholesterol was 7.37±1.09 mmol/L,which was lower than the baseline level,and the difference was statistically significant(p<0.05).3.After 3 months of hypoglycemic treatment,the diabetes medication,number and proportion of insulin application,average insulin dose per person,antiplatelet drugs and statins in the improved group were all increased compared with the baseline,with statistically significant differences(p<0.05).The number and proportion of diabetes medication cases in the unimproved group were increased compared with the baseline,and the difference was statistically significant(p<0.05).4.After 3 months of hypoglycemic treatment,WBC count,neutrophil count and monocyte count in the improved group were(7.61±1.32)109/L,(5.12±1.1)109/L,(0.54±0.13)109/L,respectively,which were 9.4%,11.0%and 21.7%lower than the baseline,with statistically significant differences(p<0.01).White blood cell count,neutrophil count,mononuclear cell count and lymphocyte count in the unimproved group showed no significant difference compared to the baseline(p>0.05).5.After 3 months of hypoglycemic treatment,the change of HbA1c in the improved group was correlated with the changes in WBC count(ρ=0.702),neutrophil count(ρ=0.782)and mononuclear cell count(ρ=0.567),with statistically significant differences(p<0.01).Subgroup analysis showed that there was a similar trend between the changes of HbA1c and the changes of WBC,neutrophil and monocytes in the improved group(p<0.05).6.After 3 months of hypoglycemic treatment,there was a significant correlation between the insulin dose and the changes of HbA1c in the improved group(ρ=0.466);there existence of obvious correlation between the insulin dose of diabetic patients and the total white blood cell count(ρ=0.693),neutrophil count(ρ=0.668),mononuclear cell count(ρ=0.423)changes(p<0.01).Regression analysis showed that insulin was an intermediary variable between changes in HbA1c and changes in total white blood cell count and neutrophil count in diabetic patients in the improved group(F=22.2,p<0.01).7.The peripheral blood granulocyte S100A8 gene,S100A9 gene,S100A12,KLF5,AGER gene,DIAPH1,GLO1 gene and IL-1 gene mRNA expression were significantly decreased,IL-4 genes and IL-6 mRNA expression were significantly increased in the improved group after 3 months,the difference was statistically significant(p<0.05);The mRNA expression of peripheral blood granulocyte-related genes in the unimproved group showed no significant difference between the baseline and 3 months later(p>0.05).Improve group of diabetic patients with peripheral blood monocytes S100A8gene,S100A12 gene,AGER,DIAPH1 and IL-1 gene mRNA expression is significantly lower baseline,IL-4 gene mRNA expression of the baseline increased significantly,the difference was statistically significant(p<0.05);mRNA expressions of S100A9,KLF5,GLO1 and IL-6 genes in peripheral blood monocytes of patients in the improved group and the unimproved group were significantly decreased from the baseline,with statistically significant differences(p<0.05).8.After 3 months of hypoglycemic treatment,there was a correlation between the changes in AGER gene expression and S100A8 gene expression(ρ=0.333),and between the changes in KLF5 gene expression and S100A12 gene expression(ρ=0.417),with statistically significant differences(p<0.01).Subgroup analysis showed a correlation between changes in AGER gene expression and changes in S100A8 gene expression(ρ=0.235)in the improved diabetic group.Conclusion:1.The white blood cell count,neutrophil count and mononuclear cell count of patients with diabetes can be significantly decreased by reducing the high glucose state.2.To reduce the hyperglycemia of diabetic patients,the changes of HbA1c were correlated with blood cell count,neutrophil count and monocyte count.3.To reduce the hyperglycemia in patients with diabetes,insulin dose is an intermediary variable between HbA1c and total white blood cell count and neutrophil count.4.Reducing the hyperglycemia in diabetic patients can reduce the mRNA expression of multiple inflammatory genes of granulocytes and monocytes. |
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