The Preliminary Mechanism Of Post-transplant Diabetes Mellitus In Kidney Transplant Recipients And Relationship Between Insulin Receptor Substrate Gene Polymorphism And Post-transplant Diabetes Mellitus

OBJECTIVE:To study the preliminary mechanism of post-transplant diabetes mellitus in kidney transplant recipients and the relationship between insulin receptor substrate gene polymorphism and post-transplant diabetes mellitus.METHODS:(1) The hospital records of kidney transplant patients were checked. At the same time, we follwed up the patients who had been done renal transplant operation and/or were followed up after operation in the Third Xiangya Hospital of Central South University. The patient’s general clinical indicators and laboratory examination indexes were collected. Using logistic regression analysis to analy the risk factors of post-transplantation diabetes mellitus in kidney transplant recipients. The diabete diagnostic standard was from the American Diabetes Association (ADA).(2)The patients who had been using tacrolimus were divied into renal transplantation diabetes mellitus or not. Clinical indicators and laboratory examination indexes of PTDM and non-PTDM were analyzed.(3) Levels of fasting insulin concentration (FINS) and C-peptide were measured in the method of enhanced chemiluminescence immunoassay analysis and direct chemiluminescence analysis respectively.(4) The genotypes of Gly1057Asp and IRS-1Gly972Arg were determined through polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) in PTDM and non-PTDM patients.RESULTS:1. A total of447adutle patients who received kidney transplants between2007and2011were included in present study.14patiens who were suffered the Type2Diabete mellitus before operation were eliminated. Occurrence of abnormal glucose metabolism in433the recipients was124(28.6%) including92(21.2%) patiens were diagnosed as PTDM,32(7.4%) were defined as IFG.2. Risk factors that highly correlated with development of PTDM included old age (P=0.000), acute rejections (P=0.015), HCV infection (P=0.004), and using Tacmous (P=0.000).3. Fasting plasma insulin concentration of PTDM and non-PTDM was19.40±14.00,15.80±10.03μU/mL respectively. There were geater than normal values (P<0.05). Fasting plasma insulin concentration of PTDM was higher than no-PTDM (P=0.046).4. Fasting plasma C-peptide concentration of PTDM and non-PTDM was1.66±1.39,1.57±0.65ng/mL respectively. There were geater than normal values (P<0.05). There are no statistical difference in fasting plasma C-peptide concentration between PTDM and non-PTDM.5. There were1057and972polymorphism in non-PTDM and PTDM. In non-PTDM patients the frequency of genotypes were and GG35%, GA42.5%, AA22.5%respectively for1057, GG97.5%, GA2.5%respectively for972. In PTDM patients the frequency of genotypes or alleles were GG32%, GA32%, AA18%for1057, GG97.4%, GA2.6%for972.6. The1057genotype distribution between non-PTDM patients and PTDM was not significantly different (P>0.05). The972genotype distribution between non-PTDM patients and PTDM was not significantly different (P>0.05).CONCLUSION:Using tacmous is the independent risk factors for development of PTDM. Tacrolimus induced hyperinsulinemia and insulin resistance is the main cause of Post-transplantation diabetes mellitus associated with tacrolimus. IRS-2Gly1057Asp and IRS-1Gly972Arg polymorphism is not related with Post-transplantation diabetes mellitus associated with tacrolimus.