Clinic Characteristics With CD38 Polymorphisms And CD38 Arg～(140) Trp Mutation Of Latent Autoimmune Diabetes Of Adults (LADA) In Chengdu

Objective: The aim of this study was to find out the clinic characteristics of the LADA patients in Chengdu, and determine whether the polymorphism at PvUII endonuclease site and Arg¹⁴⁰Trp mutation of the CD 38 gene is associated with LADA.Methods: 147 subjects were enrolled in the study. The diagnosis and classification of T1DM and T2DM were based on the 1999 WHO criteria. The diagnosis of LADA was as follows: (1) The onset of age was more than 25 years old, with obvious diabetic symptoms. (2) No ketonuria during the initial 6 months after onset. (3) Positive for islet cell autoantibodies, or OGTT 2h C-peptide lower than 0.8nmol/L. Clinical and chemistry data were analyzed, and PCR and endonuclease were used to analysis the CD38 gene.Results: The onset age of LADA was older than that of T1DM (46.84±11.04 vs. 32.18±17.19 P<0. 01), without any difference compared with T2DM (46.84±11.04 vs. 47.01±11.16 P=0. 937) . The age of 30-50 years old accounted for 79.6% in all LADA patients. 93.18% (41/44) of LADA BMI<25 kg/m²,6.81%(3/44)BMI>25 kg/m²,2.27% (1/44) BMI>27 kg/m². In T2DM 82.09% BMK25 kg/m², there were considerable overlapping with LADA. The rate in the occurrence of acute complications was T1DM, LADA and T2DM in order. The total incidence of chronic complications wasnot significantly different among the three groups. However, T2DM had the highest morbidity of diabetic retinopathy, LADA had the highest morbidity of diabetic cataract. The highest morbidity of dyslipidemia was found in T2DM. LADA had the higher level of HDL-cholestrol than T2DM and T1DM. In T2DM patients group, the positive rate for GAD-Ab was 10.45%, which was much lower than that of LADA(PO.Ol). GAD-Ab positivity was more often seen than ICA-Ab and IAA-Ab in LADA. 86.3% patients who were positive for GAD-Ab in LADA were 30-59 years old. As the age became older, the positivity declined. In OGTT+Ins+C-P test, the function of ï¿¡ islet cell of LADA was better than T1DM, but worse than T2DM. All diabetic patients had polymorphism at PvUII endonuclease site of CD38 gene. Most of them had CD38*B alleles, and CD38 BB genotype, which had no association with diabetic family history. But the polymorphism did not existed in healthy controls, all of them were CD38 BB genotype. The Arg140Trp mutation was not found in both patients and healthy controls.Conclusion: LADA is a sub type of diabetes, distinctive from T1DM and T2DM. People in 30-50 years old likely have high incidence rate of LADA. BMI is not the important factor to distinguish LADA from T2DM. The sensitivity and specificity of GAD-Ab are better than ICA-Ab and IAA-Ab for identifying LADA. The positivity of GAD-Ab will decline along with aging. Therefore, examine the glucose stimulated C-peptide response is important for the diagnosis of LADA. There are no relationship between LADA and CD38 polymorphism and CD38 Arg140Trp mutation.