The Trend Of Fasting Plasma Glucose Fluctuation And Its Related Factors After Liver Transplantation

Background and ObjectivesPost-transplant diabetes mellitus(PTDM) has great effects on complications in relation to cardiovascular system,infections,neuropsychiatric system et al,resulting in greater morbidity and affecting graft survival and patients' long-term outcome. Reports about the incidence of PTDM in liver transplant patients vary between different countries,and the risk factors of PTDM have not been identified.Studies about plasma glucose fluctuation and its related risk factors in China are limitted, most of which are univariate analysis.Our study takes a further step on the long trend of fasting plasma glucose(FPG) and lipid fluctuation and its related factors on the basis of previous study,evaluates the prevalence of PTDM within liver transplant patients in our center and the effect of FPG on patient survival and long-term complications,and discusses the possible mechanism of PTDM.MethodsIn this study,we included 703 liver transplants performed between April,2001 and December 2008.Patients excluded were previous history of steroids,data not completed and died within 3 months after orthotopic liver transplantation(OLT), leaving 524 patients for analysis,with 448 male and 76 female,the mean age of whom is 49.4 years old.Their underlying diseases were hepatic cancer,hepatitis related cirrhosis or both.Patients were divided into 3 groups(DM group,IFG group, NFG group) according to FPG previous to surgery.By comparing FPG before and 3, 6,9,12,24,36,48 and 60 months after surgery,we surveyed the trend of FPG fluctuation of each group.We also evaluated the prevalence of PTDM(3,6,9,12,36, 60 months after surgery) according to FPG.With those living over 3 years after OLT, among 32 patients of whom we conducted two point OGTT to calculate the incidence of PTDM and HOMA index.By comparing lipid data before and 1,2 and more than 3 years after surgery,we analyzed the trend of lipid fluctuation(TC,TG,HDL,LDL). Three types of grouping methods were used to compare survival rate.Patients were divided into 3 groups(DM group,IFG group,NFG group) according to the FPG previous to surgery,and to two groups(total DM group and total non-DM group) regardless of glucose before OLT,only consider FPG after OLT.And with non-DM patients before OLT,they were divided into two groups(PTDM group and non-PTDM group),survival time was compared between different groups. Meanwhile we discussed the possible risk factors of PTDM before and after transplantation with One-Way ANOVA and multivariate logistic regression method. Student's t test(One-Way ANOVA) was used to compare quantitative variables and Chi-square test was used to compare categorical variables.We used ANOVA of repeated measurements to analyze the trend of FPG and lipid fluctuation,Chi-square trend test to analyze the prevalence of PTDM,Kaplan-Meier method and log-rank test to analyze survival rate.P value less then 0.05 was considered statistically significant. Statistic analysis was done by SAS 8.2 and SPSS 13.0.Results1.During the first year after OLT,the FPG of DM group declined obviously compared to glucose before OLT,and 6,9,12 months after OLT was significantly lower.Later the glucose increased slowly and reached the highest point at the third year,and deceased at the 5^th year of OLT,which was not statisticly significant compared to glucose before OLT.The FPG of IFG group was elevated compared to glucose before OLT and most obvious months was 12 months after OLT,which was significantly higher with P value of 0.036.After that FPG remained stable then decreased slowly,glucose of the third and the 5^th year of OLT was not too much different to glucose before OLT.The FPG of NFG group elevated obviously after 3 months of OLT and remained stable and significantly higher than before OLT until the 5^th year.2.The prevalence of PTDM decreased with time,with the highest rate of 44.24% at 3 months,25.17%at the first year,17.86%at the third year and 18.18%at the 5^th year after OLT.The OGTT results indicated the incidence of PTDM was 9.38%,and the rate of IGR took 56.25%.The total prevalence of PTDM coconsidering FPG and simplified OGTT result reached 27.24%,which was much higher than the estimated rate according to FPG only.IGR group had the highest HOMA-IR and PTDM group came next,and IGR group was significantly higher than normal group(P=0.01), which indicated that insulin resistance exists at the early period of impaired glucose regulation.The HOMA-βdecreased from normal group,IGR group to PTDM group, and PTDM group was significantly lower than normal and IGR group(P value both less than 0.01),which indicated that with the worsening of impaired glucose metabolism,the degeneration ofβcell progresses with time. 3.DM group,IFG group and NFG group were similar at lipid level before OLT, and the TC,TG and LDL were at a relatively low range.After transplantation,the TC, TG and LDL of each group all elevated and the HDL had no rule to follow.The lipid metabolism disorder in relation to PTDM maybe manifested as high level of TC and LDL.4.DM group vs IFG group and IFG group vs NFG group both had significantly different survival time,while no statistic difference happened between DM group and IFG group.After OLT,total DM group compared with total non-DM group,PTDM group compared with non-PTDM group both had lower survival rate.And higher rate of sepsis and chronic renal insufficiency appeared in PTDM group.5.Univariate analysis indicated that liver function and fasting plasma glucose pre-operation,the use of interleukin 2 receptor antagonist and calcineurin inhibitor were significantly related with PTDM,while multivariate logistic regression indicated fasting plasma glucose pre-operation and steatosis of donor liver had positive relation with PTDM,their OR value was 1.853 and 1.803 respectively.And the use of interleukin 2 receptor antagonist was negatively related with PTDM with OR value of 0.427.Conclusions1.Liver transplantation can improve the fasting plasma glucose of diabeted patients before transplantation,and helps to improve the level of TC,TG and LDL.2.The prevalence of PTDM was relatively high at the early stage of transplantation,but decreased with time.If we only detect patient's FPG,we may underestimate the prevalence of PTDM.3.Plasma glucose level did affect patient's survival and complication,whatever DM happened before or after OLT,it can reduce survival rate.4.We found that abnormal fasting plasma glucose and liver function pre-operation,steatosis of donor liver and use of interleukin 2 receptor antagonist and calcineurin inhibitor were risk factors in relation to PTDM.