The Effect Of Pioglitazone On High Density Lipoprotein Function In Patients With Type 2 Diabetes And Telephone Follow-up Intervention

With the development of the economy and the growth of aging population,the diabetes rate appears an increasing tendency year by year,and the age of onset gradually becomes younger.It has become the third serious chronic disease following tumor,cardiovascular and cerebrovascular disease in the world.Diabetes itself is not terrible,the terrible aspect is the related acute and chronic complications,and the pathological basis of chronic complications is atherosclerosis（as）.Therefore,in clinical reasonable selection of medication is crucial to stabilize blood sugar levels in order to prevent atherosclerosis.As is known to all,high density lipoprotein（HDL）plays an important role in delaying the development of atherosclerosis,and pioglitazone（PIO）as representatives of thiazolidined-ione drugs,studies show the drug has elevated HDL effect,but in diabetes patients vivo HDL may change glycation and oxidation.Therefore,whether PIO can improve HDL function needs further research.In addition,it is worth noting that diabetes as a chronic disease,the patient’s compliance with the control of blood sugar is also very important to delay complications.Telephone follow-up as one main form of the outside hospital continuing nursing,its purpose lies in that patients can still continue to accept disease rehabilitation related health education and health services after discharge,it can extends the hospital nursing service to outside hospital effectively.At present,some studies have discussed the effect of telephone follow-up on the compliance of patients with diabetes mellitus,and the results are not consistent.Therefore,this study will use the telephone follow-up to intervent patients’compliance,and explore the effect of telephone follow-up on the compliance of patients with diabetes and the impact on HDL function.PartⅠ THE INTERVENTION STUDY OF PIOGLITAZONE ON HIGH DENSITY LIPOPROTEIN FUNCTION IN TYPE 2 DIABETES PATIENTSObjective Diabetes is one of the main chronic diseases that threaten human health,and diabetic dyslipidemia is an important cause of cardiovascular complications and the leading cause of death in patients with T2DM.This study is to observe the influence of pioglitazone on patients with T2DM HDL function and common risk factors of cardiovascular and cerebrovascular disease in order to provide new perspective for the improvement of drug treatment of T2DM.Methods 1.Patient inclusion,exclusion criteria and pioglitazone intervention:110 T2DM patients were collected from October 2014 to May 2015 in Tai’an Central Hospital according to WHO or the American Diabetes Association（ADA）diagnostic criteria,all patients signed informed consent.Exclusion criteria:（1）received pioglitazone treatment;（2）with stroke,myocardial infarction,occlusion of serious chronic complications of arterial sclerosis;（3）obvious disorder of digestion and absorption of chronic functional bowel disorders;（4）severe infection and tumor,trauma,surgery,burns and other stress;（5）accompanied by other endocrine,autoimmune diseases or connective tissue sick;（6）serious heart,liver,kidney disease;（7）the current or previous history of bladder cancer or associated with unknown hematuria.10 patients were not included;therefore,100 patients were collected in the end.They were divided into control group（50）and pioglitazone group（50）according to the drug they take.All patients received diabetes health education in the hospital,the control group patients take oral hypoglycemic drugs routine and PIO group patients take pioglitazone tablets 30mg/d on this basis.2.Collection,preservation and detection of Blood samples:Both before and after intervention we collect fasting venous blood from all the patiants,serum was preservated on the static centrifugal-80℃,dectecting fasting blood glucose（FPG）,postprandial blood glucose（PPG）,glycosylated hemoglobin（HbA1c）,urea nitrogen（BUN）,creatinine（Cr）,cholesterol（TC）,triglyceride（TG）,high density lipoprotein cholesterol（HDL-C）,low density lipoprotein cholesterol（LDL-C）,apolipoprotein A（ApoA）,apolipoprotein B（ApoB）,lipoprotein a（Lp（a））,high sensitive C reactive protein（hs-CRP）were tested in the laboratory of Tai’an Central Hospital by Hitachi 7600-210ISE automatic biochemical.3.High density lipoprotein separation:high density lipoprotein was isolated by density gradient centrifugation and its concentration was determined by BCA method.4.Detection of RCT function of HDL:Western blot was applied to detect the content of apoA-1 in serum,³H labeled cells were used to detect the plasma and HDL mediated cholesterol efflux efficiency.5.Detection of anti-oxidant and anti-inflammatory function of HDL:The activity of PON-1 and MPO in serum was detected by kit and use kit detected the content of MDA in HDL₃.The content of TNF-and IL-6 in cell supernatant was detected by ELISA kit.6.Detection of anti adhesion function of HDL:ox-LDL injury of human umbilical vein endothelial cells（HUVECs）was used for 6 hours,and then HDL was added to protect it for 24 hours,under the fluorescence microscope mononuclear cell adhesion was observed,protein was extracted and Western blot was used to detect the expression of ICAM-1,VCAM-1 expression.7.Detection anti-apoptosis function of HDL:ox-LDL injury of human umbilical vein endothelial cells（HUVECs）was used for 6 hours,and then HDL was added to protect it for 24 hours.The cell apoptosis of HUVECs were detected by flow cytometry.8.Statistical analysis:all data analysis using the statistical software SPSS 20.0,measurement data performed（（?）±s）,count data performed frequency.Two sample measurement data of group compared with paired t-test and between groups compared with the independent sample t-test,count data using chi square test,P≤0.05 means statistically significant difference.Results 1.General information:There was no significant difference in general information and blood glucose level between the two groups before and after the intervention（P>0.05）.After 3 months,within group comparison shows that FPG,PPG and HbA1c levels decreased（P<0.05）in control group.In addition to reduced FPG,PPG and HbA1c in pioglitazone group,the waist circumference,and blood pressure（SBP,DBP）also decreased significantly（P<0.05）;compared with the control group after the intervention,SBP of pioglitazone group was decreased by 8.5%.2.The effects of pioglitazone on atherosclerosis risk factors:Before the intervention,there were no differences in plasma lipoprotein,apolipoprotein and inflammatory factor Hs-CRP between the two groups（P>0.05）.After 3 months,the control group of TC,LDL-C level was decreased and levels of TG,HDL-C was elevated（P<0.05）and LDL-C,apoB and hs-CRP was decreased and HDL-C,ApoA was increased（P<0.05）in pioglitazone group;compared with that of control group after the intervention,in pioglitazone group ApoA rose was elevated by11.72%and hs-CRP was reduced by 21.39%.3.The effect of pioglitazone on HDL function（1）HDL mediated the function of RCT:There was no significant difference in plasma apoA-1 concentration and cholesterol efflux rate between the two groups before the intervention（P>0.05）.After intervention for 3 months compared with control group,the content of apoA-I in the pioglitazone group in the serum of the patients was increased by11.29%,plasma mediated cellular cholesterol efflux efficiency was increased by 19.41%;however between the two groups of equivalent apoa-1 mediated cholesterol row ability had no significant difference（P>0.05）.（2）Anti-oxdiant function of HDL:There was no significant difference in plasma oxidative stress level between the two groups before the intervention（P>0.05）.After intervention for 3 months,in pioglitazone patients,plasma MPO activity was decreased significantly（P<0.01）,but compared with control groupm,it had no obvious change.The plasma PON-1 activity were significantly higher than control group and before intervention（P<0.05）.HDL was obtained in plasma by ultracentrifugation.3 months after the intervention,compared with before intervention and control groups,MDA content in HDL were significantly decreased and HDL anti LDL oxidation effect were significantly increased.（3）Anti-adhesion function of HDL:cell adhesion assay showed that before intervention in the two groups of patients,HDL did not show obvious anti monocyte adhesion ability;3 months after the intervention,in the two groups of patients,HDL can inhibit monocyte adhesion to endothelium and pioglitazone group is more obvious.Western blotting experiments showed that:compared with model group and control group,HDL in the prognosis of patients with pioglitazone decreased the expression of ICAM-1and VCAM-1.（4）Anti-inflammatory function of HDL:The detection of cell secretion of inflamematory mediators of TNF alpha and IL-6 found that compared with model group and control group,pioglitazone stem of HDL in the prognosis of the patients was significantly inhibited the endothelial cell secretion of tumor necrosis factor alpha;and compared to model group,also reduces the IL-6 secretion（P<0.05）.（5）Anti-apoptosis function of HDL:there was no statistically significant difference after pioglitazone intervention in the function of HDL anti-apoptosis（P>0.05）.Conclusion 1.T2DM patients with pioglitazone can prevent atherosclerosis better;2.Pioglitazone can increase the level of HDL-C and increased plasma cholesterol mediated efficiency and enhances the function of HDL anti-oxidant,anti-inflammatory,anti-adhesion,but anti-apoptosis function is not affected;3.The effect of pioglitazone in prevention of atherosclerosis may be related to the improvement of HDL function.Part Ⅱ THE EFFECT OF TELEPHONE FOLLOW UP ON PATIENTS’COMPLIANCE AND CHANGE OF CONDITION WITH TYPE 2 DIABETES MELLITUSObjective In the course of treatment,the compliance of patients with diabetes is one of the important factors that influence the curative effect,how to improve the T2DM patient compliance is the urgent problem to be solved.Telephone follow-up as a way of continuing nursing care,has a certain impact on patient compliance and reduce readmission rates of patients with chronic diseases.In this experiment,investigated patient’s treatment compliance and analysis of factors affecting patient compliance;through the implementation of telephone follow-up intervention in type 2 diabetic patients on pioglitazone,discussion of telephone follow-up on the compliance of therapy in patients with type 2 diabetes.Methods 50 T2DM patients were collected from October 2014 to May 2015 in Tai’an Central Hospital.They were regarded as telephone follow-up intervention group.We regarded pioglitazone group in part Ⅰ as control group.All patients were prescribed taking pioglitazone tablets and received diabetes health education.They took care of themselves according to the contents of the guide books which we provided.Intervention group received telephone follow-up on the basis of this.The content mainly includes discharge health education brochure and telephone follow up at different time.Health education includes guide patient medication compliance,reasonable diet,and movement,check regularly,monitor blood glucose,prevent and delay complication occurrence.At the same time,in the follow-up process we should pay more attention to the interaction with the patient and answer the questions which they felt puzzled.Before and after the intervention,the patients filled in general information,questionaire of compliance of diabetes patients and social support scale.Analysis of diabetes patients compliance status and influenction factor,effect of telephone follow-up on patients’ compliance.Collect blood samples before and after the intervention,detect related biochemical indexes.Results 1.Treatment compliance of type 2 diabetes patients were poor,which the highest score is the compliance of medication,the lowest score is periodic,and the factors of influence the treatment compliance were education,income and the course of disease.2.General information and physiological index:before intervention there were no significant difference in the two groups of T2DM patients in all aspects of gender,age,occupation,body weight,body mass index,blood glucose,blood lipid（P>0.05）;after telephone follow-up intervention 3 months,there was significant difference in waist circumference,blood pressure blood glucose,high sensitivity C-reactive protein,glycerin three fat,high density lipoprotein cholesterol,low density lipoprotein cholesterol,apolipoprotein A and apolipoprotein B（P<0.05）.Compared with pioglitazone group,fasting blood glucose,triglyceride and high sensitivity C-reactive protein levels were significantly decreased（P<0.05）,the other indexes change little（P>0.05）.3.Patients’ compliance and social support: before intervention,there were no significant difference in the two groups of patients with treatment compliance and social support status in all dimensions（P>0.05）,but the scores of a reasonable diet,regular exercise,blood glucose monitoring and regular follow-up is low;after telephone follow-up intervention,patients’ scores in reasonable diet,regular exercise,blood glucose monitoring and regular follow-up significantly improved（P<0.05）,social support total score and subjective scores increased significantly（P<0.05）.Patients in control group treatment compliance and social support condition did not change significantly（P>0.05）.Conclusion 1.Patients with type 2 diabetes treatment compliance is not ideal,the influence factors are the degree of education,income and the course of disease;2.Telephone follow-up can improve the treatment compliance of T2DM;3.Telephone follow-up has a certain effect on the blood glucose and cardiovascular risk factors in patients with T2DM.