The Efficacy Of Liraglutide In Type 2 Diabetes Mellitus Patients With Long Duration And Its Effect On Islet Cell Function

ObjectivesTo observe the effects of liraglutide on glucose metabolism,lipid metabolism,weight-related indexes,blood pressure in the treatment of type 2 diabetes mellitus with long duration and discuss the the changes of isletβcell function,glucagon and somatostatin level after 24 weeks of treatment.MethodsWe selected 121 patients with type 2 diabetes who had a disease course of more than 10 years,body mass index≥25kg/m~2,and were treated with insulin combined with at least one oral hypoglycemic agent but their blood glucose level was not up to standard(glycosylated hemoglobin 7%),and at last 88 patients were enrolled.After reduce the blood glucose by insulin pump,patients were randomly divided into experimental group and control group.In the experimental group,liraglutide was administered subcutaneously.In the control group,insulin and/or oral hypoglycemic agents(without dipeptidine-4 inhibitors)were administered.The treatment objectives in both groups were:fasting blood glucose<7 mmol/L,postprandial blood glucose<10 mmol/L,glycosylated hemoglobin<7%.Before enrollment,the height,weight,waist circumference,hip circumference and blood pressure of the patients were measured and recorded.Blood lipids,blood glucose and glycosylated hemoglobin were detected,and glucose tolerance,insulin and c-peptide release tests were conducted.Serum levels of insulin,C-peptide,glucagon and somatostatin were measured at 0,60 and 120 points after glucose loading.After 24 weeks of observation,the above indicators were retested and adverse reactions were recorded.SPSS 21.0was used to process the data,and the changes of indicators treatment were compared.Results1.Blood glucose indexThe fasting blood glucose,2 hours blood glucose,glycosylated hemoglobin of the experimental group and the control group after treatment were lower than baseline,but there were differences between the experimental group and the control group.When glycosylated hemoglobin<6.5%was used as the standard,there was statistical difference between the two groups on the compliance ratio.2.Weight-related indicatorsBody mass index,waist circumstance and waist-hip ratio of the experimental group were all lower than baseline level,and hip circumstance had no difference to baseline.There was no difference in weight-related indicators between the control group and baseline.3.Changes in blood pressure and lipid metabolism indexes at 24 weeks after treatmentSystolic blood pressure and diastolic blood pressure in the experimental group were all lower than that before treatment,triglycerides,cholesterol,LDL cholesterol,and very low density lipoprotein cholesterol were lower than baseline,and HDL was higher than baseline.There was no difference in blood pressure and lipid metabolism between the control group and baseline.4.The relationship between the reduction of glycosylated hemoglobin or body mass index in the experimental group and the baseline after 24 weeks of treatmentThe decrease of glycosylated hemoglobin in the experimental group was positively correlated with baseline hba1c level,baseline FBG level,very low density lipoprotein level,and triglyceride level.The decrease of body mass index in the experimental group was positively correlated with baseline of body mass index and baseline of waist circumference.5.Changes in isletβcell function after 24 weeks of treatmentIn the experimental group,fasting C-peptide,C-peptide at 1 hour and 2 hours,HOMA-βwere higher than baseline,and HOMA-IR was lower than baseline.There was no difference between control group and baseline on isletβcell function.6.Isletαcell function changes after 24 weeks of treatmentThere was no significant difference in the area under the curve of glucagon,fasting glucagon,glucagon at 1 hour,the area under the glucagon between the experimental group and the baseline level,and the glucagon level at 2 hours was higher than baseline.The fasting glucagon,glucagon at 1 hour and 2 hours,and the area under the curve of glucagon were higher than baseline.In the experimental group,glucagon levels were increased compared with baseline in those with successful glucose level and those with weight loss.7.Isletδcell function changes after 24 weeks of treatmentSomatostatin levels were significantly higher at each point in the experimental group and the control group than baseline,and somatostatin levels in the experimental group were significantly higher than those in the control group.8.Adverse reactionsThe main adverse reactions in the experimental group were nausea and diarrhea,with a total of 5 cases of hypoglycemia.There were 4 cases of hypoglycemia in the control group.There was no difference in the incidence of hypoglycemia between the two groups.9.Effect of liraglutide on insulin useAt discharge,There was a significant statistical difference between the two groups of using insulin.After 24 weeks of treatment,the ratio of using insulin in the experimental group was lower than the control group.Conclusion1.Liraglutide can improve the metaboilic level in overweight or obesity type 2 diabetes with long duration,including improve glucose metabolism and blood pressure,reduce weight and waist circumstance,and improve central obesity,and its main adverse reaction is gastrointestinal reaction,at the same time the liraglutide do not increase the risk of hypoglycemia and decrease the ratio of using inlulin.2.For type 2 diabetes patients with long duration,liraglutide can improve isletβ cell function and reduce insulin resistance,improve isletδcell function,but has no inhibitory effect on isletαcell in the secretion of glucagon.3.For the type 2 diabetes patients with long duration,baseline glycosylated hemoglobin,fasting glucose,triglycerides,and very low density lipoprotein are the determinants for the improvement of blood glucose,and baseline body mass index and waist circumference were the determinants for the improvement of body mass index.