The Effects Of Intensive Control Blood Glucose, Blood Pressure And Blood Lipid On The Intima-media Thickness,Serum Level Of Advanced Glycosylation End Products(AGEs) And Their Soluble Receptor In Type 2 Diabetic Patients

ObjectiveThe incidence of Type 2 diabetes mellitus (T2DM) is significantly correlated with age obviously, and rises year by year. By 2010, the number of type 2 diabetic patients has approached 100,000,000 in our country. The macro-vascular complications is the most important reason for mutilation and death caused by T2DM. Therefore, the research of preventing and treating macro-vascular complications is significant especially. Now, the therapeutic tool of T2DM includes conventional therapy and intensification therapy mainly. Some researchers have begun to compare the different effects of these two therapeutic methods, however, the number of participants and follow-up period were small. Hence, to compare the value of intensive controlling of blood glucose (BG), blood pressure (BP)and blood lipid (BL)and conventional controlling of BG, BP, BL, after 5 years follow-up, we record the changes of the intima-media thickness (IMT) of carotid artery, iliac artery and femoral artery of 160 T2DM patients.Advanced glycation end products (AGEs) have been implicated in diabetic complications, as AGEs are formed by a series of chemical reactions following glycation. But the relationship between AGEs , their soluble receptor (sRAGE) and the extent of macro-vascular complications has not been reported before. So through measuring the serum level of AGEs and sRAGE when the research finished, determine the association between AGEs, sRAGE and macro-vascular complications.Methods1. Selected 160 patients of newly diagnosed T2DM who were referred to Changhai Hospital in Shanghai. They were randomly divided into three groups: 33 in the Group A, the control group treated with BG, BP intensive control,88 in the Group B, the control group treated with BG, BP,BL intensive control, 39 in the Group C, the control group treated with BG, BP, BL conventional control.2. Record the age, gender, height, weight of patients, past history of hypertension and dyslipidemia, and smoking history. Measure fasting postpradial glucose(FPG),2 hour postpradial glucose(2hPG), systolic blood pressure(SBP), diastolic blood pressure (DBP) , every month , measureFPG,2hPG, SBP,DBP,Body mass index (BMI), hemoglobin A-c(HbAlc),total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol(HDL-C), fasting plasma insulin (FINS),liver and renal function, every 6 monthes in Intensively controlling group. In conventional controlling group measure FBG, 2hPG, SBP, DBP, HbAlc, TC, TG, LDL-C,HDL-C, BMI, FIS ,liver and renal function, every 6 monthes. And the IMT of carotid artery, iliac artery and femoral artery in them were observed every year in three groups to last 5 years. Compare the changes of IMT of carotid artery, iliac artery and femoral artery, and other correlated physiological indices.3. The serum level of AGEs, sRAGE were measured and compared between different groups. And analyze the relation between these two indices with the forward level of BG, and between these indices with the change of IMT of artery, respectively, at end of the experiment.Results1. Following 3 years intensive control, the level of IMT of iliac artery and femoral artery, 2hPG, TC and TG deScrased, whereas, the level of FINS inScrased significantly, comparing to the stage of pretreatment(P<0.05).2.After treatment for 5 years, at end of the experiment, there is no difference of BP between three groups. The level of FPG, 2hPG, HbAlc, FINS in group C were higher than that in group A and B(P<0.05).The level of HDL-C in group C were lower than that in group A and B(P<0.05).3. There is no difference of sRAGE between three group (P=0.427). However, serum level of AGEs was significantly deScrased after intensive controls(P=0.009).The level of AGEs is much higher in group C than in group A and B significantly (P<0.01).4. In the observation period, the increasing of IMT of carotid artery and femoral artery in group C is faster than those in other groups` showing significant difference(P <0.05). It didn`t happen to iliac artery (P >0.05).5. Multinomial Regression analysis was used to find out the risk factors on the IMT of femoral artery: AGEs,SBP,age, and AGEs was the important risk factor of femoral artery(β=0.163,P =0.091). HDL-C,2hPG and age are risk factors of carotid artery , and Scr and age is correlated with iliac artery.6. The ratio of sRAGE and HbA1c measured at the terminus point was negatively correlated with the mean of HbA1c recorded in the past 5 years(HbA1c′)(r=-0.417, P<0.001),meanwhile, the ratio was also negatively correlated with the fluctuation of HbA1c′(r=-0.309, P<0.001). Conclusion1.After intensive control in early stages, the occurrence and development of diabetic macro-vascular disease can be changed, and 2hPG,TC,TG of newly diagnosed T2DM patients can decrease significantly .2.Intensive control is important to control the growth of IMT of carotid artery, and femoral artery ,and improve FPG,2hPG,FINS,HbA1c,HDL-C in newly diagnosed T2DM patients. However, it is ineffective to iliac artery. Hence, intensive control can protect the macro-vessels in a centain extent.3. AGEs,SBP,age are the risk factors of IMT of femoral artery. The long-term intensive control can decrease the accumulation of internal AGEs obviously. Though this way, positive intervention of BP,Scr and 2hPG can be useful to delay the diabetic macro-vascular disease for T2DM patients, and for elderly especially .4. Measure the serum level of sRAGE, then calculate sRAGE /HbA1c.The ratio was more valuable for the fluctuation of BG in the past long-term than single time HbA1c data.5.There is no difference between intensive control and conventional therapy in the influence of liver and renal function.