The Clinical Clues Of Screening Latent Autoimmune Diabetes In Adults (LADA) And The Relevance Between Polymorphism Of LYP/PTPN22 Gene And LADA

ObjectiveTo compare the clinical features of latent autoimmune diabetes mellitus in adults(LADA) and type 2 diabetes(T2DM),and find the clinical clues to identify LADA from type 2 diabetes in earlier period.And to explore the relationship between polymorphism of protein tyrosine phosphatase nonreceptor 22(PTPN22) gene and LADA.Methods205 unrelated subjects in Shanghai with latent autoimmune diabetes mellitus in adults (LADA group) and 240 type 2 diabetics(T2DM group)and 100 healthy volunteers(control group) was included in the study.LADA group and control group were divided into male subgroup(n=100 vs 36) and female subgroup(n=100 vs 69),the clinical features and biochemical index were compared between 110 LADA patients and T2DM group. PCR-restriction fragment length polymorphism(PCR-RFLP) was performed to detect the genotypes polymorphism of-1123G/C and + 1858C/T area in PTPN22 gene,and the genotypic frequency,allelic frequency,and clinical characteristics were compared between LADA and control group.Results1.The body mass index,fasting,30min,120min levels of C-peptide in LADA group were lower significantly than T2DM group(P＜0.05).There was no significant difference of fasting glucose and postprandial glucose between two groups.2.HbAlc,the frequency of typical diabetic symptoms,and incidence of ketonuria at diabetes onset of LADA group were higher than T2DM group,but the ratio of patients with diabetic family history,incidence of retinopathy and nephropathy in LADA patients were lower significantly than patients with T2DM. 3.The bibasil logistic regression analysis indicated that BMI and△C-p were independent risk factors of positive GADA.In LADA group,the F-Cp levels and△C-p of patients with GADA titer＞30 000U/L were lower than patients with low GADA titre.4.Three genotypes of PTPN22 gene at -1123 site,GG GC and CC,were detected in Shanghai Hans.The most frequent genotype and allele of the PTPN22-1123 were GC and CC. Two genotypes,CC and CT,were detected,while no TT were detected for +1858C/T polymorphism.The most frequent genotype and allele of the PTPN22+1858 were CC and C.5.The significant difference of the G/C,C/C genotype frequencies of PTPN22 gene was observed between control group and LADA group(odds ratio[OR]=1.22,95%CI=1.00-1.50, P=0.015).However,there was no significant difference in +1858C/T genotypic frequencies (CC,CT)and allelic frequencies(C,T) between two groups(P＞0.05).6.There were significant differences of-1123G/C genotypic(GG,GC,CC) frequencies in male- or female subgroups between LADA and control group.Furthermore,in LADA group, the higher frequency of C alleles was found in male subgroup of LADA than female subgroup(OR=1.32,95%CI=1.21-2.26,P =0.013).Conclusions1.Low BMI and C-peptide are clinical clues of identifying LADA from type 2 diabetic patients,the diagnosis of LADA is depended on detecting the autoantibodies against antigen of isletβcells.The patients with GADA titer higher than 30 mU/L have lower C-peptide level.2.There was significant difference of-1123G/C genotypic polymorphism between control group and LADA in Shanghai Han ethnics.3.The LADA in Han ethnics of Shanghai were associated with the promoter -1123G/C SNP of PTPN22 gene,but not the +1858C/T variant.