| Objective: As an important part of diabetic chronic complications, diabetic macrovascular complications have become one of the main reasons,which could lead to death.However, the mechanisms are still unclear. Recently more and more studies show that inflammatory cytokines play an important role in the development of diabetic macrovascular complications. Some researches from domestic and overseas that reveal the serum level of insulin in Type 2 diabetic mellitus with macrovascular complications is higher than that of patients without macrovascular complications.Some scholars believe that hyperinsulinemia is one of the key factors which could lead to diabetic macrovascular complications,what is worse,it may cause the incidence of tumor, hypoglycemia and all-caused mortality increasing.While,the relationships between inflammatory factors and hyperinsulinemia keep unclear. Now numerous treatment options are available for Type 2 diabetes,but the studies of intensive glucose-lowering therapy(INT), including ADVANCE, VADT, ACCORD, suggest that the great use of insulin does not significantly decrease cardiovascular outcomes in type 2 diabetes or perhaps might increase all-caused mortality.However,the reason of the above result is unclear. This study aims to evaluate the effect of continuous subcutaneous insulin injection(CSII) and multiple subcutaneous insulin injection(MSII) on the level of serum insulin and inflammatory factors(including TNF-α、IL-1) as well as to discuss the relatianships between the serum level of insulin and inflammatory factors by observing the changes of serum level of insulin and inflammatory factors in overweight type 2 diabetic mellitus, further more,to privide more definite data to support reasonable treatment of type 2 diabetes mellitus and its complications in clinical.Methods: Sixty patients with type 2 diabetic mellitus, with poor glycaemic control(FBG>7.0mmol/L, 2h PG>10.0mmol/L) and overweight(Body mass index, BMI≥24kg/m2) in the First Hospital of Qin Huangdao from January,2014 to January, 2015 were recruited in this study.They were divided into two groups randomly:(1) CSII(n=30,with insulin aspart).(2) MSII(n=30,with insulin aspart before meals and insulin glargine at 21:00). Meanwhile thirty overweight(BMI≥24kg/m2)subjects of normal glucose tolerance confirmed with OGTT were selected as control group(NC)(n=30). All patients’ gender, age, duration of diabetes, history of smoking and drinking were collected, and height, weight, blood pressure were measured without changing glycaemic therapy on the day of admission. Serum levels of inflammatory factors(including TNF-α、IL-1), fasting insulin,fasting plasma glucose, 2-h plasma glucose(Diabetic diet), 2-h plasma insulin(Diabetic diet), TG, CHOL, HDL-C, LDL-C, C-peptide(0h, 2h) in all subjects were measured on the first morning after admission and the forth morning after glycaemic control(FBG≤7.0mmol/L, 2h PG≤10.0mmol/L). Lipid-lowering drugs and drugs those can affect the secretion and function of insulin were not used during the study.Statistical analysis was performed using SPSS13.0 software package. P<0.05 was considered significant for all statistical analysis. The normal distribution data was described by Mean ± SD. T-test was employed to compare difference between two groups. Rectilinear correlation and multiple linear regression analysis were employed to analyze those elements.Results:1 Compared with control group, the serum levels of TG, CHOL, FBG, 2h PG, FINS, TNF-α, IL-1 were significantly increased in T2 DM group(P<0.05). 2 Before therapy, there was no significant differences in age, BMI, FBG, 2h PG, C-P and other laboratory data between CSII group and MSII group(P>0.05). 3 Comparison of laboratory data in the two test groups after glycaemic control:3.1 After glycaemic control, the serum TNF-α level was decreased from 123.12±40.23ng/ml to 82.8 ± 40.17ng/ml in CSII group(P<0.05), and 124.46±36.04ng/ml to 85.19±18.43ng/ml in MSII group(P<0.05); the serum IL-1 level was decreased from 91.59±22.08ng/ml to 38.14±11.13ng/ml in CSII group(P<0.05), and 92.45±35.40ng/ml to 47.43±15.84ng/ml in MSII group(P<0.05); compared with MSII group, the serum IL-1 level in CSII group was lower after glycaemic control(P<0.05). 3.2 The level of FBG was decreased from 11.55±2.96mmol/L to 6.02±1.09mmol/L in CSII group(P<0.05), and 11.30±4.66mmol/L to 6.54±0.81mmol/L in MSII group(P<0.05); the level of 2h PG was decreased from 15.74±5.38mmol/L to 8.65±2.06mmol/Lng/ml in CSII group(P<0.05) and 14.18±3.94mmol/L to 8.89±1.18mmol/L in MSII group(P<0.05). 3.3 The serum FINS level was decreased from15.69±8.98 m IU/L to 8.36±3.44 m IU/L in CSII group(P<0.05), and 16.47±13.19 m IU/L to 14.64±13.04 m IU/L in MSII group(P<0.05); the serum PINS level was decreased from 51.56±25.73 m IU/L to 24.47±15.42 m IU/L in CSII group(P<0.05), and 51.58±39.05 m IU/L to 44.58±32.17 m IU/L in MSII group(P<0.05); compared with MSII group, the serum FINS and PINS levels in CSII group were lower after glycaemic control(P<0.05). 3.4 The HOMA-IR was decreased from 8.78±6.93 to 2.61±1.31 in CSII group(P<0.05), and 9.49 ± 13.07 to 4.22 ± 3.87 in MSII group(P<0.05); compared with MSII group,the decreasing amplitude of HOMA-IR in CSII group was more significant than in MSII group(P<0.05). 3.5 The time of reaching target FBG was(2.68 ± 0.98)d in CSII group, and(6.32±1.34)d in MSII group(P<0.05); that in 2h PG was(6.32±1.34)d in CSII group, and(8.52±1.59)d in MSII group(P<0.05). 3.6 The insulin dose used in CSII group was(29.6±12.12)u,however,in MSII group was(43.3±12.8)u(P<0.05). 3.7 The serum TG level was decreased from 1.94±1.18 mmol/L to 1.49±0.62 mmol/L in CSII group(P<0.05), and 1.77±0.89 mmol/L to 1.76±1.44 mmol/L in MSII group(P>0.05); the serum CHOL level was decreased from 5.39±1.02 mmol/L to 4.52±0.81 mmol/L in CSII group(P<0.05), and 5.38±1.20 mmol/L to 4.00±0.80 mmol/L in MSII group(P<0.05); The serum LDL-C level was decreased from 3.54±0.92 mmol/L to 2.93±0.77 mmol/L in CSII group(P<0.05), and 2.85±0.89 mmol/L to 2.41±0.77 mmol/L in MSII group(P<0.05); The serum HDL-C level was decreased from1.07±0.24 mmol/L to 1.02±0.24 mmol/L in CSII group(P>0.05), and 1.24±0.79 mmol/L to 1.07±0.27 mmol/L in MSII group(P>0.05). 4 Analysis of related factors of IL-1 and TNF-α:4.1 There was no statistically significant linear correlation between age, BMI, SBP, DBP, CHOL, HDL-C, LDL-C, 2h PG, PINS and IL-1; however, the serum level of IL-1 was poitively correlated with TG 、 FBG 、 FINS, and the pearson correlation coefficients were as follows:0.268, 0.876, 0.501(P<0.05); moreover, a multiple linear regression analysis was made with IL-1(Y) as the dependent variable, TG(X1), FBG(X2) and FINS(X3),gender(X4),smoking(Y=1,N=0)(X5),drinking(Y=1,N=0)(X6)as the the variables.The regression equation was:Y =14.829+1.507X1+6.308X2+0.144X3(P<0.05).The multiple correlation coefficient(R) =0.879, indicating that the correlativity of actual IL-1 value and the regression equation estimated IL-1value was 0.879. The determination coefficient(R2) =0.773, indicating that IL-1could be explained by TG, FBG and FINS with a percentage of 77.3%. 4.2 There was no statistically significant linear correlation between age, BMI, SBP, DBP, TG, CHOL, HDL-C, LDL-C, 2h PG, FINS, PINS and TNF-α; however,the serum level of TNF-α was poitively correlated with FBG,and the pearson correlation coefficients was 0.367(P<0.05);furthermore, a multiple linear regression analysis was made with TNF-α(Y) as the dependent variable, FBG(X1),gender(X2),smoking(Y=1,N=0)(X3),drinking(Y=1,N=0)(X4) as the the variables. The regression equation was: Y^=82.809+3.506X1(P<0.05).The correlation coefficient(R) =0.367, indicating that the correlativity of actual TNF-α value and the regression equation estimated TNF-α value was 0.367. The determination coefficient(R2) =0.135, indicating that TNF-α could be explained by FBG with a percentage of 13.5%. 5 Analysis of related factors of FINS and PINS: 5.1 There was no statistically significant linear correlation between age, SBP, DBP, TG, CHOL, HDL-C, LDL-C and FINS; however,the serum level of FINS was poitively correlated with FBG,BMI and the pearson correlation coefficients were as follows:0.374, 0.409(P<0.05). 5.2 There was no statistically significant linear correlation between age, SBP, DBP, 2h PG, and PINS; however, the serum level of PINS was poitively correlated with BMI, and the pearson correlation coefficients was 0.399(P<0.05). 6 Analysis of related factors of the decreasing amplitude of IL-1 and TNF-α: 6.1 In CSII group, the pearson correlation coefficients between the decreasing amplitude of FINS, FBG, HOMA-IR and IL-1 were as follows: 0.689, 0.663, 0.674(P<0.05); and the pearson correlation coefficients between the decreasing amplitude of FINS, FBG, HOMA-IR and TNF-α were as follows:0.645, 0.563, 0.657(P<0.05); moreover, multiple linear regression analysis was made with the decreasing amplitude of IL-1(Y1) and TNF-α(Y2) as the dependent variables, FINS(X1), FBG(X2) and HOMA-IR(X3) as the the variables. The regression equations were:Y1=34.097+1.157X1+2.395X2(P<0.05), the multiple correlation coefficient(R) =0.728, indicating that the correlativity of actual decreasing amplitude of IL-1 value and the regression equation estimated decreasing amplitude of IL-1 value was 0.728. The determination coefficient(R2) =0.530, indicating that the decreasing amplitude of IL-1could be explained by the decreasing amplitude of FINS and FBG with a percentage of 53.0%; Y2=27.579+2.048X3(P<0.05), the multiple correlation coefficient(R) =0.657, indicating that the correlativity of actual decreasing amplitude of TNF-α value and the regression equation estimated decreasing amplitude of TNF-α value was 0.657. The determination coefficient(R2) =0.431, indicating that the decreasing amplitude of TNF-α could be explained by the decreasing amplitude of HOMA-IR with a percentage of 43.1%. 6.2 In MSII group, the pearson correlation coefficients between the decreasing amplitude of FINS, FBG, HOMA-IR and IL-1 were as follows:0.689, 0.663, 0.674(P<0.05); and the pearson correlation coefficient between the decreasing amplitude of FBG and TNF-α was 0.458(P<0.05); moreover, a multiple linear regression analysis was made with the decreasing amplitude of IL-1(Y) as the dependent variable, FINS(X1), FBG(X2) and HOMA-IR(X3) as the the variables. The regression equation was: Y=12.508+2.497X1-1.051X2+6.904X3(P<0.05), the multiple correlation coefficient(R) =0.89, indicating that the correlativity of actual decreasing amplitude of IL-1 value and the regression equation estimated decreasing amplitude of IL-1 value was 0.89. The determination coefficient(R2) =0.791, indicating that the decreasing amplitude of IL-1could be explained by the decreasing amplitude of FINS, FBG and HOMA-IR with a percentage of 79.1%.A linear regression analysis was made with the decreasing amplitude of TNF-α(Y) as the dependent variable, decreasing amplitude of FBG(X) as the the variable. The regression equation was: Y=23.244+3.369X(P<0.05).The correlation coefficient(R) =0.48, indicating that the correlativity of actual decreasing amplitude of TNF-α value and the regression equation estimated decreasing amplitude of TNF-α value was 0.48. The determination coefficient(R2) =0.21, indicating that decreasing amplitude of TNF-α could be explained by decreasing amplitude of FBG with a percentage of 21%.Conclusions: 1 The serum levels of inflammatory factors(including TNF-α、IL-1) in overweight T2 DM patients are significantly higher than in control group. 2 The serum level of IL-1 is poitively correlated with TG、FBG、FINS,and the serum level of TNF-α is poitively correlated with FBG in overweight T2 DM patients. 3 The correlations of FINS, FBG with IL-1and TNF-α show that reducing the serum of FINS and blood glucose could effectively improve the inflammatory states and insulin resistance in T2 DM. 4 Insulin pump therapy in the control of blood glucose, reducing serum insulin level,improving insulin resistance and inflammatory status has significant advantages. |
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