An Analysis Of Iislet Fuction And GLP-1 In Seperate Glucose Tolerance And Different Type 2 Diabetes Course

Objective:Type 2 diabetes mellitus(T2DM)is a metabolic disease,which has the complex pathogeny,Genetic,environment and others contribute to this metabolic disease.With the deep study of T2 DM more and more concepts have been accepted that islet αand β cell are both playing important roles in the T2 DM pathology.In recent years,it has been found that gut endocrine cell can secret glucagon-like peptide 1(GLP-1),which binding with specific receptors and then via a strictly glucose-dependent manner to stimulate insulin and inhibit glucagon secretion.In addition to its hypoglycemic effect on the islet cell,GLP-1 participates in the glucose metabolic and insulin sensitivity in peripheral tissues,inhibiting gastrointestinal motility expecially gastric emptying and food intake.Basd on those researches,it is widely used in the GLP-1 receptor agonist and DPP-4 inhibitor which can highly increase GLP-1 concentration in vivo.Impaired secretion of GLP-1 has been suggested to contribute to the deficient incretin effect in patients with T2 DM.Recent studies,however,have not always supported this notion.The aim of this study was to investgate the islet fuction and GLP-1 concentration in seperate glucose tolerance and different diabetes course via oral glucose tolerance test(OGTT),find the predictor of GLP-1 secretion,and realize the incretins action on the development of diabetes,therefore provide the rationale of diabetes prevention and targeted treatment.Methods:1 This cross-sectional study was involved 120 subjects,who were randomly sampled from the department of endocrinolgy and physical examination of the Third Hospital affiliated to Hebei Medical Univercity.According to the result of OGTT,the subjects were divided into 30 normal glucose tolerance(NGT),30 impaired glucose regulation(IGR)and 60 diabetes mellitus(DM).According to the duration of diabetes,the DM group was divided into DM1(duration < 5years)and DM2(duration≥ 5years),which was 30 cases.The clinical data included age,sex,duration of diabetes,drugs intake,body weight,height,waist and hip circumstances,SBP,DBP,HbA1 C,TC,TG,LDL-C,HDL-C,glucose concentration(0,30,60.120min),insulin,C-peptide,glucagon and GLP-1 concentration(0,30,120min),calculating body mass index(BMI)and waist-to-hip-ratio(WHR),HOMA-IR,IAI,HOMA-β,△I30/△G30,latephase insulin secretion,MBCI,the area under the curve(AUC)of glucose,insulin,C-peptide,GLP-1 and glucagon were recorded.2 Statistical analysis:SPSS 20.0 was used for statistic analyses.Results are reported as mean±SE.General and islet function statistical calculations were carried out using One-way ANOVA.Glucose insulin,Cpeptide,glucagon,GLP-1 secretion in seperate time data calculation were repeated-measures ANOVA.Pearson corrlation was used to examine associations bewteen GLP-1 and general statistic,islet cell function.AUCglp of multiple linear regression model was bulided by multiple linear stepwise regression.A two-sided P value<0.05 was taken to indicate significant differences.Results:1 Comparation of insulin secretion,insulin sensitivity index and AUC of all hormons in four groups:Compaired with NGT,IGR group,HOMA-β,late-phase insulin secretion of DM was significantly decresed(P <0.05).From NGT to DM group the △I30/△G30 and insulin sensitivity were significantly descended gradually(P<0.05).AUCg in four groups DM2>DM1 > IGR > NGT group(P < 0.05),AUCins and AUCcp of IGR was significantly higher(P < 0.05),There were no differences in the plasma concentrations of GLP-1(P < 0.05).AUCgc of NGT was significantly lower(P<0.05).2 Factors affecting GLP-1 secretion:Multiple linear stepwise regression showed that GLP-1 concentration was positively associated with age and negatively associated with fasting glucose,glucagon(the standardizeation regression coefficient were respectively 0.196,-0.184,-0.249).Conclusions:1 Insulin resistance and αcell dysfunction is to continue exsiting in T2 DM development,and the β cell function progressively decays over time.2 In the stage of different glucose tolerance and different T2 DM course exsist no decrease in GLP-1 secretion,suggesting that GLP-1 secretion is not accordance with islet β cell function.Impaired insulin secretion in abnormal glucose tolerance may not attribute to defect in GLP-1 secretion.3 Some basal conditions probably affect GLP-1 secretion such as age,plasma glucose and glucagon,but the detail mechanisms need to be found.