Correlation Between Islet Autoantibodies,uric Acid And Islet β-cell Function In Type 2 Diabetes Mellitus

Part 1 Serum insulin-to-C-peptide ratio and prediction of the presence of insulin antibodies in type 2 diabetes with exogenous insulin therapyObejective:The aim of the study is to develop a model for predicting the presence of insulin antibodies（IAs）in type 2 diabetes patients.Methods:IAs,plasma insulin and C-peptide have been measured in type 2 diabetes with or without exogenous insulin therapy.Performances of the predicting models were estimated using receiver operating characteristic（ROC）curves.Results:Compared to the group without insulin treatment,patients with insulin therapy had higher prevalence of IAs+（19.45%vs 5.5%,p<0.001）.Two models for predicting the presence of IAs in type 2 diabetes patients with insulin therapy before hospitalization were developed.The ROC curves indicated the fasting insulin-to-C-peptide ratio（insulin/C-peptide）and the AUC_insulin-to-AUC_C-peptide ratio(AUC_insulin/AUC_C-peptide)have the good predicting property for the positivity of IAA with the AUC[0.834（95%CI 0.784–0.884）,p<0.001,0.824（95%CI 0.771-0.877,p<0.001）,respectively].Serum fasting insulin/C-peptide>0.089 had 82.83%sensitivity for predicting the presence of IAs and with 78.05%specificity.With a cutoff of 0.0236,the AUC_insulin/AUC_C-peptide had considerable sensitivity（72.37%）and specifity（84.63%）for predicting the the presence of IAs.Conclusions:Fasting serum insulin/C-peptide and AUC_insulin/AUC_C-peptide can be suitable index to predict the presence of IAs in type 2 diabetes with exogenous insulin therapy.Part 2 Islet autoantibodies and β-cell function in clinical patients with type 2 diabetesObjective To investigate the prevalence of islet autoantibodies and their relationships to β-cell function and metabolic control in clinical patients with type 2 diabetes.Methods Islet autoantibodies were measured in clinical patients with type 2 diabetes.Patients with islet autoantibodies were compared with those without islet autoantibodies,and β-cell function,metabolic control and blood pressure were assessed.Results Compared to the group without insulin treatment,the patients with insulin treatment before hospitalization showed significantly higher prevalence of Ab+（24.36% vs.9.05%,p<0.001）,IAA+（19.49% vs.4.86%,p<0.001）.All calculated parameters of β-cell function and metabolic control were not different between the Ab+ and Ab-patients with type 2 diabetes without insulin treatment before hospitalization.In the group with insulin treatment before hospitalization,the Ab+ patients showed significant lower Cp AUC180/HOMA2-IR,Cp AUC180/GAUC180,C0-30min/G0-30 min,i Cp AUC180 and i Cp AUC180/i GAUC180 compared to the Ab-patients.There were also no significant differences in Hb A1 C,lipid level and blood pressure between two groups.Conclusions Exogenous insulin administration can induce the production of islet autoantibodies,which was positively associated with the probability of aggressive impairment of β-cell function in clinical patients with type 2 diabetes.Part 3 Correlation of serum uric acid and islet β-cell function in male type 2 diabetesObjective: To investigate the correlation of serum uric acid and β-cell function in male type 2 diabetes.Methods: A total of 510 male patients who were clinically diagnosed as type 2 diabetes and received treatment at the First Affiliated Hospital of Nanjing Medical University between December 2014 and April 2016 were enrolled in this study.The body parameters,blood uric acid,biochemical indexes and islet autoantibodies were measured.The function of islet β-cell and insulin resistance were evaluated in parallel with mixed-meal tolerance test.Results: The linear correlation analysis between the two groups showed that the serum uric acid was positively correlated with C0-30min/G0-30min（r=0.122,P=0.006）,i Cp AUC180/i GAUC180（r=0.304,P < 0.001）,HOMA2-% β（r=0.267,P < 0.001）,Cp AUC180（r=0.328,P < 0.001）and HOMA2-IR（r=0.248,P<0.001）.The serum uric acid levels of the hyperuricemia and the normal uric acid groups were（480.63±57.39）and（304.22±59.38）μmol/L respectively.Compared to the normal uric acid group,the hyperuricemia group showed significant higer HOMA2-IR（1.76±0.80 vs.1.34±0.71,p=0.001）,HOMA2-%β（89.15±47.64 vs.67.18±30.88,p=0.001）,△ C30/△ G30（146.43±166.05 vs.75.00±184.45,p=0.009）,Cp AUC180（5991.02±2549.86 vs.4577.51±1970.00,p=0.001）and i Cp AUC180/i GAUC180（222.29±175.86 vs.140.79±104.81,p=0.001）.Adjusting unbalanced factors between two groups,all calculated parameters of β-cell function and insulin resistance were also different between two groups.When Analyzed the islet autoantibody negative patients,the hyperuricemia group had higher HOMA2-IR、 HOMA2-%β、△ C30/△ G30、 Cp AUC180 and i Cp AUC180/i GAUC180（all p<0.05）compared to the normal uric acid group.Adjusting unbalanced factors between two groups,higher HOMA2-% β,Cp AUC180 and i Cp AUC180/i GAUC180 were also showed in the hyperuricemia group.But there were no statistical differences in HOMA2-IR（F value =2.14,p=0.144）and △ C30/△ G30（F value =3.66,p=0.057）between two groups.Conclusions: The serum level of uric acid is positively correlated to islet β-cell function and insulin resistance evaluated in parallel with mixed-meal tolerance test.Metabolic syndrome and islet autoantibodies may be involved.