Evaluation Of Pancreatic ?-Cell Function Using The Arginine Stimulation Test

BackgroundDue to the aging population and changes in lifestyles,people's living standards have continuously improved.However,the incidence of diabetes mellitus(DM)has also risen year by year.Timely and effective evaluation of pancreatic ?-cell function is of clinical significance for the early diagnosis,early intervention,assessment of disease,evaluation of curative effect,and prognosis of DM.At present,several methods are available for the evaluation of pancreatic ?-cell function,including the evaluation index of pancreatic ?-cell function,the pulse secretion test of insulin,the Bergman minimum model,the high glucose clamp,the oral and venous glucose stimulation tests,and other non-sugar stimulation tests.The oral glucose tolerance test is a gold standard for evaluating the status of glucose metabolism,and it is also a classical method for detecting insulin release from pancreatic ?-cells.The steamed bread meal test(SBMT)is the most widely used method clinically.Non-sugar stimulation tests mainly include pancreatic hyperglycemia experiments,tolbutamide stimulation test and the arginine stimulation test(AST),which has been widely used in clinic in recent years.In this study,the AST and SBMT were compared clinically,and the application value of the AST was evaluated.The objective of this study was to evaluate pancreatic ?-cell function using the AST and SBMT.ObjectiveMethodsThe study population(n = 118,all with type 2 DM)was recruited from the First Affiliated Hospital of Anhui Medical University between April 2011 and February 2012.All patients signed an informed consent form.The first SBMT or AST was randomly chosen by drawing lots.After 1 week,the alternative test was carried out.DM was diagnosed on the basis of the 2014 American Diabetes Association criteria,and classification was based on the insulin release test or the C-peptide release test.The exclusion criteria were as follows: patients with trauma,infection and other stress states;patients with serious liver and kidney damage,patients with acute diabetic complications and patients with an acute or chronic disease history which could affect the secretion of pancreatic islets.For the SBMT,patients discontinued all medications at least 12 h prior to the test;fasting was started 8 h before the test;prior to the test,patients sat quietly for 30 min between 07:00 and 08:00 h;fasting blood samples were collected from an elbow vein using an indwelling needle;blood glucose,insulin and C-peptide were measured.Then,after eating 100 g of steamed bread made of flour(brand: Fuqiang),venous blood samples were obtained at 30,60,120 and 180 min,and blood glucose,insulin,and C-peptide levels were measured.For the AST,patients discontinued all medications at least 12 h prior to the test;fasting was started 12–14 h prior to the test;patients lay in the horizontal position at exactly 09:00 h,their the cubital veins were punctured,and 4 ml of fasting venous blood samples were obtained;20 ml of 25% arginine was then injected(Shanghai Xinyi Jinzhu Pharmaceutical Co.,Ltd.)and the injection was complete within 30 s;an electronic stopwatch was used to record the time;2 ml of venous blood was collected at 2,4,6 and 8 min after the injection;the blood samples were centrifuged at 1500 r/min and stored at-20?;insulin and C-peptide levels were measured at 0,2,4,6 and 8 min.Results:1.Changes in blood glucose,insulin,and C-peptide levels at different time points in the AST and SBMT Paired t-test results showed that there were significant differences in baseline blood glucose and fasting blood glucose(P < 0.001),but no significant difference in fasting insulin(P = 0.497)in the AST and SBMT.After the SBMT,blood glucose levels at 0,30,60,120 and 180 min differed significantly(F = 126.450,P < 0.001).Following injection of arginine,there were significant differences in blood glucose levels at 0,2,4,6 and 8 min(F = 12.302,P < 0.001),blood glucose levels following the AST lower than blood glucose levels following the SBMT(P < 0.001)at each time point.2.The AST may reflect the function of pancreatic ?-cell in diabetic patients Data from the two tests were analyzed using Pearson correlation analysis.The results showed that the area under the AST insulin curve was positively correlated with the area under the SBMT insulin curve,insulin peak,HOMA-IR and HOMA-IS;the correlation coefficients were 0.572,0.805,0.068,and 0.099,respectively.The area under the SBMT insulin curve was also positively correlated with the AST insulin secretion peak,insulin secretion mean value,HOMA-IR and HOMA-IS;the correlation coefficients were 0.683,0.528,0.317,and 0.213,respectively.3.Area,mean and peak value of the AST insulin curve When the AST and SBMT were compared,the correlation coefficients of peak value,mean value,and peak difference of the AST and SBMT were 0.768,0.792,and 0.882,respectively.Simple linear regression analysis indicated that the regression coefficient ? was 0.5(P < 0.001)for the area under the insulin curve(Fig.1),was 0.07(P < 0.001)for AST mean insulin and the area under the SBMT insulin curve(Figure 2), and was 0.07(P < 0.001)for the AST insulin peak and the area under the SBMT insulin curve(Figure 3).4.Pearson correlation and partial correlation analysis In the AST,BMI(body mass index)was positively correlated with fasting insulin and C-peptide levels,and the correlation coefficients were 0.154 and 0.459,respectively.There was a negative correlation between the course of the disease and fasting insulin and C-peptide levels;the correlation coefficients were-0.60 and-0.45,respectively.However,gender had little effect on insulin secretion with correlation coefficients of 0.004 and 0.003,respectively.5.Adverse effects During the AST,12 patients experienced a transient and slight intraoral metallic sensation or transient tingling and burning sensation in the tongue,which was tolerable and disappeared within 1 min of the injection.The incidence of this adverse effect was 10.17%.In addition,22 patients reported a slight burning sensation in the tongue,which disappeared within 5–15 s.The incidence of this adverse effect was 18.74%.Before the test,six patients experienced dizziness and palpitations,which disappeared after lying down,and the patients then continued with the test.Accelerated heart rate,increased respiratory frequency,gastrointestinal discomfort,elevated blood pressure,panic,dizziness,nausea,vomiting,chest tightness,and other adverse reactions were not observed.None of the subjects discontinued the test.Conclusions: 1.Responses to the AST and SBMT were different.Although the AST could cause fluctuations in blood glucose,the amplitude was lower than that of the SBMT.2.These results suggest that the AST and SBMT show similar results in reflecting pancreatic ?-cell function.3.In terms of the evaluation of pancreatic ?-cell function,the area,mean value,and peak value of the AST insulin curve showed few influencing factors and the calculations were simple.4.With age and sex adjustment,C-peptide levels were associated with BMI(P < 0.001),while insulin levels were not associated with BMI(P = 0.172).5.Adverse effects,such as a metallic or burning sensation in the mouth,were observed during the AST.However,these adverse effects were tolerable.