The Influencing Factors Of The Vascular Endothelial Injury In Newly Diagnosed Type 2 Diabetes And The Effect Of Transient Continuous Subcutaneous Insulin Infusion Therapy

Part 1 The study of the influencing factor of the vascular endothelial injury in newly diagnosed type 2 diabetesObjective: To investigate the correlation of the injury of vascular endothelial cell, inflammation condition and innate immunity mediated by toll like receptor 4(TLR4) in newly diagnosed type 2 diabetes (T2DM).Methods: Newly diagnosed T2DM (n=93) and euglycemic persons (n=78) were recruited. The serum soluble E-selectin(sE-selectin) was used to evaluate the injury of vascular endothelial cell; the serum high sensitivity C reactive protein(hsCRP) and soluble CD14(sCD14) were used to assess the inflammation condition and innate immunity mediated by TLR4 separately.Results: (1) The waist circumference, waist-to-hip ratio(WHR), systolic blood pressure(SBP), diastolic blood pressure(DBP), fasting blood sugar(FBS), 2 hours postprandial blood sugar(2hPBS), serum cholesterol(CHOL), triglyceride(TG), free fatty acid(FFA) and alanine aminotransferase(ALT) of newly diagnosed T2DM group were significantly higher than that of euglycemic group, and high density lipoprotein cholesterol(HDL-C) was lower(P<0.05). (2) The level of serum sE-selectin, hsCRP and sCD14 in newly diagnosed T2DM was higher than in englycemic persons[sE-selectin(21.3±7.7)ng/ml vs (32.9±11.4)ng/ml; hsCRP(1.45±1.21)mg/L vs (2.37±1.45)mg/L]. There were significant differences in the first two markers. However, the difference in the last did not exist. (3) After matching blood pressure, blood sugar and blood lipid between obesity subjects and normal weight subjects in the group of newly diagnosed T2DM, the weight, body mass index(BMI), waistline, hip circumference, WHR, fasting insulin(FINS), insulin resistance index(HOMA-IR), B cell function (HOMA-B), ALT, hsCRP, sCD14 and sE-selectin in obesity subjects were higher than those in normal weight subjects, and there were not significant difference in the last two markers. (4) In the newly type 2 diabetes, the weight, BMI, waistline, hip circumference, WHR, SBP, DBP, TG, FINS, 2hPINS, HOMA-IR, HOMA-B, ALT, hsCRP, sCD14 and sE-selectin were higher in T2DM with metabolic syndromes(MS) than those without MS. There were not significant differences in the last four markers. (5) The weight, BMI, waistline, hip circumference, SBP, FFA, hsCRP, sCD14 and sE-selectin in obesity subjects of euglycemic group were significant higher than those in normal weight subjects(P<0.05～0.01). (6) The serum sE-selectin was correlated with FBS, 2hPBS, glycosylated hemoglobin(HbA1c), sCD14 and HOMA-IR in the diabetes group. The serum sCD14,2hPBS and WHR were the chief influencing factors of serum sE-selectin.Conclusions: (1) It exists vascular endothelial injury, low grade inflammation and activation of innate immunity mediated by TLR4 in newly diagnosed T2DM, especially in obesity subjects. (2) The injury of vascular endothelial cell, low grade inflammation and activation of the innate immunity mediated by TLR4 are present in obesity person whether or not with glycometabolism disorder. (3) In the newly diagnosed T2DM, vascular endothelial injury is closely correlated with glycometabolism, the degree of insulin resistance and innate immunity condition mediated by TLR4. Part 2 The study of the improving effect of transient continuous subcutaneous insulin infusion therapy on vascular endothelial injury in newly diagnosed type 2 diabetesObjective: To explore the impact of transient continuous subcutaneous insulin infusion(CSII) therapy on vascular endothelial injury, inflammation condition and innate immunity mediated by TLR4.Methods: Ten patients with newly diagnosed T2DM accepted a two-week course of intensive CSII therapy with insulin aspart. Intravenous glucose tolerance test (IVGTT) and hyperinsulinemia euglycemia clamp test were performed before and after CSII in the state of fasting.Results: (1) After the transient CSII therapy, the blood sugar of IVGTT, the area under the curve of the blood sugar, HbA1c, CHOL, LDL-C and ALT were significantly decreased(P<0.05). (2) After the transient CSII therapy, the insulin release of IVGTT(except the fasting insulin) was significant improved(P<0.05). The area under the curve of insulin(AUC_INS) became larger and acute insulin response(AIR) during IVGTT was improved[AUC_INS: (41.9±21.4)mU/L vs (85.3±45.3)mU/L, P<0.01; AIR: (-19.78±24.27)mU/L vs (20.38±25.56)mU/L, P<0.01]. (3) The glucose infusion ratio(GIR) in the course of hyperinsulinemia euglycemia clamp test were increased greatly after two-week CSII therapy[GIR: (3.46±1.66) mg·kg^-1·min^-1 vs (7.14±2.37) mg·kg^-1·min^-1, P<0.01]. Moreover, the HOMA-IR decreased and HOMA-B increased significantly (P<0.01). (4) After the transient CSII therapy, the serum sE-selectin and sCD14 were significantly decreased[sE-selectin: (49.0±20.6)ng/ml vs (28.5±12.8)ng/ml, P<0.01; sCD14: (584.1±140.7) ng/ml vs (446.3±97.5)ng/ml, P<0.01], and the serum hsCRP also decreased(P >0.05).Conclusions: (1) The transient CSII therapy in newly diagnosed T2DM can improve glucose and lipid metabolism, insulin resistance, the first phase secretion of insulin and promote the recovery of B cell function. (2) The transient CSII therapy can inhibit inflammation condition, regulate innate immunity mediated by TLR4 and repair vascular endothelial injury.