Expert consensus on diabetes mellitus after solid organ transplantation in adults / 器官移植

Post-transplant diabetes mellitus (PTDM) is a common endocrine and metabolic disorder after adult solid organ transplant (SOT), affecting 10% to 40% of recipients. PTDM has been associated with increased mortality, heightened risk of infections, graft-related complications and cardiovascular diseases, all of which seriously threaten the quality of life and long-term survival of recipients. According to recent studies and the domestic healthcare system, this consensus provides a comprehensive overview of the epidemiology, risk factors, pathogenesis, screening and diagnosis, treatments, prevention strategies, cardiovascular risk factor management and microvascular complications associated with PTDM, in order to further standardize the diagnosis and treatment of PTDM. The objective is to standardize the comprehensive management of PTDM with the aim of enhancing the long-term quality of life and clinical outcomes for SOT recipients.

Risk factors associated with diabetes after liver transplant

ABSTRACT Objective: Post-transplant diabetes mellitus (PTDM) is a common metabolic complication after liver transplant that negatively affects a recipient's survival and graft function. This study aims to identify risk factors associated with diabetes after liver transplant. Materials and methods: This is a cross-sectional study conducted from September to November 2019. Data collection was performed by chart review, and patients were divided into 3 groups: patients without diabetes mellitus (DM), patients with pre-transplant diabetes mellitus, and patients with PTDM. Results: Two hundred and forty-seven patients' medical charts were screened, and 207 patients were included: 107 without DM, 42 with pre-transplant DM, and 58 with PTDM. The leading cause for liver transplant was hepatitis C, followed by hepatocellular carcinoma secondary to alcohol. There was a higher exposure to tacrolimus in patients without DM ( P = 0.02) and to ciclosporin in patients with pre-transplant DM, compared to others ( P = 0.005). Microscopic interface inflammatory activity was more severe in patients without DM as well as those with PTDM ( P = 0.032). There was a higher prevalence of steatosis in recipients with pre-transplant DM than there was in others ( P < 0.001). Multivariate logistic regression identified the following independent risk factors for DM: cirrhosis due to alcohol, hepatitis C, and triglycerides. For PTDM, these independent risk factors were cirrhosis due to alcohol, hepatitis C, and prednisone exposure. Conclusion: Alcoholic cirrhosis is a risk factor for PTDM in liver recipients. Liver transplant recipients with a pre-transplant history of cirrhosis due to alcohol, hepatitis C, and prednisone exposure deserve more caution during PTDM screening.

Advances in pharmacotherapy for post-transplant diabetes mellitus / 解放军医学杂志

Post-transplant diabetes mellitus (PTDM) often occurs after solid organ transplantation, and treatment of PTDM is different from that of type 2 diabetes mellitus, the current research in this field is increasing gradually. The present paper summarizes the characteristics of blood glucose change in PTDM, risk assessment, the safety of hypoglycemic drugs, and the effect of immunosuppressive drugs on blood glucose in PTDM patients, and focuses on the efficacy and safety of new hypoglycemic drugs in PTDM patients, as well as the clinical research evidence such as the type of immunosuppressant used and the formula of administration has been summarized, so as to select a more optimized PTDM treatment options.

The predictive value of glycated albumin in renal transplant recipients with post-transplant diabetes mellitus / 西安交通大学学报(医学版)

Objective: To investigate the predictive value of glycated albumin (GA) in renal transplant recipients (RTRs) with post-transplant diabetes mellitus (PTDM). Methods:We conducted a retrospective study. We recruited patients aged ≥18 years old who had no pre-transplant diabetes and received the first renal transplantation (RT) in The First Affiliated Hospital of Xi'an Jiaotong University from January 2017 to December 2017. Patients with pre-transplant thyroid dysfunction, post-transplant impaired fasting glucose, renal graft failure, transplant nephrectomy, loss of follow-up, or death were excluded. According to the diagnostic criteria of PTDM in 2014, on the basis of the results of fasting plasma glucose (FPG) at least twice after 45 days of RT, the patients were divided into post-transplant diabetes mellitus group (PTDM group) and post-transplant normal fasting glucose group (PTNFG group). Each patient was followed up for one year. After comparison of the clinical data of the two groups, SPSS software was used for analyzing the data. Receiver operating characteristic (ROC) curve was plotted to evaluate the predictive value of GA for PTDM. Results: In this study, a total of 282 RTR were screened, and 72 patients were not qualified. We recruited 210 patients, with 21 in PTDM group and 189 in PTNFG group. The levels of body mass and body mass index (BMI) in PTDM group were higher than those in PTNFG group (P0.05). GA in PTDM group was higher than that in PTNFG group at 7 days and 14 days after RT (P<0.05). ROC curve analysis showed that the predictive value of GA was the highest at 14 days after RT, its area under ROC curve (AUC) was 0.749. GA was 14.55% at 14 days after RT. Youden index was the largest, with the sensitivity of 57.1% and the specificity of 87.3%. The positive likelihood ratio was 4.5, the negative likelihood ratio was 0.49, the positive predictive value was 57.1%, and the negative predictive value was 87.3%. Conclusion: GA can predict RTR with PTDM at 14 days after RT.

Analysis of risk factors for post-transplant diabetes mellitus in patients with renal transplants / 中华内分泌外科杂志

Objective To investigate the incidence and risk factors contributing to post-transplant dia-betes mellitus (PTDM) in kidney transplant recipients within one year post-transplantation. Methods A total of 293 non-diabetic kidney transplant recipients were retrospectively analyzed. Patients were divided into non-PTDM group and PTDM group according to the diagnostic criteria of diabetes mellitus. The incidence of PTDM was cal-culated and the potential risk factors of PTDM were analyzed by univariate and multivariate Logistic regression analysis. Results Among the 293 non-diabetic patients, 36 patients developed PTDM within 1 year, with an in cidence of 12.3％. Multivariate Logistic analysis showed that age (OR 1.055, 95％ CI 1.014-1.098, P=0.009), body mass index [odd ratio (OR) 1.231, 95％ confidence interval (CI) 1.084-1.398, P=0.001], polycystic kidney as the primary disease (OR 1.508, 95％ CI 1.006-2.262, P=0.047), 2-hour postprandial blood glucose (OR 1.186, 95％CI 1.04-1.53, P=0.011), HbA1c (OR 1.732, 95％ CI 1.075-3.428, P=0.015) and 1-hour postprandial blood C-pep-tide (OR 0.869, 95％ CI 0.804-0.939, P=0.001) were independent risk factors for PTDM in kidney transplant re-cipients within 1-year post-transplantation. Conclusion Patients with older age, obesity, polycystic kidney as the primary disease, higher level of HbA1c and 2-hour postprandial blood glucose, and lower level of 1-hour post-prandial blood C-peptide may have higher risk of developing PTDM.

Analysis of risk factors for post-transplant diabetes mellitus in patients with renal transplants / 中华内分泌外科杂志

Objective@#To investigate the incidence and risk factors contributing to post-transplant diabetes mellitus (PTDM) in kidney transplant recipients within one year post-transplantation.@*Methods@#A total of 293 non-diabetic kidney transplant recipients were retrospectively analyzed. Patients were divided into non-PTDM group and PTDM group according to the diagnostic criteria of diabetes mellitus. The incidence of PTDM was calculated and the potential risk factors of PTDM were analyzed by univariate and multivariate Logistic regression analysis.@*Results@#Among the 293 non-diabetic patients, 36 patients developed PTDM within 1 year, with an incidence of 12.3%. Multivariate Logistic analysis showed that age (OR 1.055, 95% CI 1.014-1.098, P=0.009) , body mass index [odd ratio (OR) 1.231, 95% confidence interval (CI) 1.084-1.398, P=0.001], polycystic kidney as the primary disease (OR 1.508, 95% CI 1.006-2.262, P=0.047) , 2-hour postprandial blood glucose (OR 1.186, 95% CI 1.04-1.53, P=0.011) , HbA1c (OR 1.732, 95% CI 1.075-3.428, P=0.015) and 1-hour postprandial blood C-peptide (OR 0.869, 95% CI 0.804-0.939, P=0.001) were independent risk factors for PTDM in kidney transplant recipients within 1-year post-transplantation.@*Conclusion@#Patients with older age, obesity, polycystic kidney as the primary disease, higher level of HbA1c and 2-hour postprandial blood glucose, and lower level of 1-hour postprandial blood C-peptide may have higher risk of developing PTDM.

Prognosis of post-transplant diabetes mellitus in recipients with steatotic donor livers / 中华肝胆外科杂志

Objective To study the risk factors and prognosis of post-transplant diabetes mellitus (PTDM) in recipients with steatotic donor livers.Method The clinical data of 182 patients who underwent liver transplantation from donors with liver steatosis in Tianjin First Central Hospital from June 2002 to December 2010 were retrospectively analyzed.There were sixteen patients with PTDM and one hundred sixtysix without PTDM.The clinical data of these patients were compared and the risk factors were evaluated by COX regression analysis.The 1-,3-,5-year cumulative survival rates were analyzed after liver transplantation.Result The variables which included sex,pretransplant serum creatinine level,model for end-stage liver disease (MELD) score,intraoperative red blood cell transfusion,and post-transplant biliary complications were significantly different between the two groups.Multivariate Cox regression analysis showed that living-donor,pretransplant fasting blood glucose and post-transplant biliary complications could affect the survival time of patients in PTDM group.The 1-,3-and 5-year cumulative survival rates in the PTDM group were 81.3％,68.8％ and 62.5％,which were significantly lower than those in the non-PTDM group (95.2％,86.1％ and 80.7％ respectively,P ＜ 0.05).Conclusions Living-donation,pretransplant fasting blood glucose and post-transplant biliary complications had a worse prognosis in the PTDM group.A comparatively better long-term survival after liver transplantation can be achieved by reducing the risk factors and the occurrence of PTDM.

Effect of tacrolimus on short chain fatty acids in rats / 器官移植

Objective To investigate the changes of short chain fatty acids (SCFA) induced by tacrolimus (FK506) in rats and evaluate its effect on blood glucose levels. Methods Ten SD rats were divided into the FK506 group and control group (n=5 in each group). In the FK506 group, the rats were received a subcutaneous injection of FK506 (3 mg/kg) +sunflower oil solution containing 10% ethanol daily for consecutive 4 weeks. In the control group, the rats were received a subcutaneous injection of an equivalent amount of sunflower oil solution containing 10% ethanol for consecutive 4 weeks. During the drug injection period, the body mass of rats was measured every week in two groups. After the drug injection period, blood glucose level, SCFA content in the blood and feces samples were measured in two groups. Results Compared with the control group, the relative body mass of rats in the FK506 group was significantly lower at the 2nd, 3rd and 4thweeks (all P<0.01). Compared with the control group, the blood glucose levels of rats in the FK506 group were significantly increased at 0, 30, and 60 min after giving glucose (P<0.01-0.05). Compared with the control group, the contents of acetic acid, propionic acid, isobutyric acid, butyric acid, isovaleric acid and valeric acid in the feces sample were significantly lower in the FK506 group (P<0.01-0.05). Conclusions FK506 can upregulate the blood glucose level in rats, which is probably induced by the decrease of SCFA content in rat feces.

An analysis on the prevalence and risk factors of post-transplant diabetes mellitus after renal transplantation / 中华内分泌代谢杂志

Objective To explore the incidence of post-transplant diabetes mellitus (PTDM) by means of fasting plasma glucose (FPG) and other associated risk factors in patients surviving for more than 1 year after renal transplantation.Methods A total of 428 non-diabetic patients,who underwent kidney transplantation from 1 January,1993 to 31 December,2008,were followed up in order to ascertain the prevalence of PTDM after transplantation and other associated risk factors by means of FPG.Results Of the 428 patients,87 developed PTDM (20.3％) within a mean follow-up of (5.65 ± 3.68) years after renal transplantation.The onset of PTDM occurred in 57 patients (65.5％ of total PTDM) primarily within the first year after transplantation.Univariate analysis showed that older age,body mass index (BMI),smoking history,family history of diabetes mellitus,deceased donor transplantation,hepatitis C virus infection,cytomegalovirus infection,FPG before transplantation as well as 1 week after transplantation,total cholesterol and triglyceride before transplantation,switching from cyclosporine to tacrolimus(FK506),and peak plasma concentration of cyclosporine in the first 6 and 12 months were associated with the onset of PTDM.The prevalence of PTDM was markedly elevated in the group who has cyclosporine converted to FK506 (P＜0.05),but not in the group with cyclosporine converted to rapamycin.By multivariate analysis,FPG before transplantation,age,BMI,and deceased donor transplantation were independently associated with the onset of PTDM.Conclusions There is high incidence of PTDM in patients following renal transplantation; and early diagnosis,treatment as well as prevention are mandatory.

Analysis on the changing trend of fasting plasma glucose and its impact on prognosis after renal transplantation / 中华内分泌代谢杂志

ObjectiveTo explore the long-term fluctuation of fasting plasma glucose (FPG) and its effect on prognosis in patients surviving for more than 1 year after renal transplantation.MethodsFour hundred and forty-six patients underwent kidney transplantation from January,1993 to December,2008.According to preoperative FPG levels,patients were divided into diabetic,impaired fasting glucose (IFG),and normal fasting glucose (NFG)groups. The changing trend of FPG level was observed and analyzed. For 428 non-diabetic patients before transplantation,the prevalence and different outcomes of post-transplantation diabetes( PTDM ) according to FPG after transplantation were analyzed.The characteristics of the patients with persistent PTDM ( P-PTDM ) and transient PTDM (T-PTDM) were compared.The incidence of complications and patient survival between the PTDM group and non-PTDM groups were also compared.ResultsFPG level was increased early and then decreased in patients after renal transplantation.Of the 428 patients,87 developed into PTDM ( 20.3％ ) including 15 T-PTDM patients ( 17.2％ of total PTDM ),who eventually recovered to NFG or IFG.Compared with P-PTDM group,the incidence of acute rejection episodes was higher for T-PTDM ( P =0.043 ).The incidence of infections,hypertension,and dyslipidemia within the first year,was higher in PTDM group compared with non-PTDM group but patient survival was not different within a mean follow-up of ( 5.65 ± 3.68 ) years.ConclusionPTDM will not be permanent and may recover to NFG or IFG in the course of the disease.Acute rejections are associated with the onset of T-PTDM.The overall patient survival is not affected by PTDM,although complications,such as infections,hypertention,and hyperlipidemia are more frequently encountered in PTDM patients.

Long-term impacts of post-transplant diabetes mellitus on transplant recipients / 中华内分泌代谢杂志

Post-transplant diabetes mellitus (PTDM) remains a major clinical challenge following transplantation.This article reviews the long-term negative impact of PTDM on transplant recipients, including impaired allograft function, poor patient survival, accelerated onset of diabetic complications, a significantly higher rate of infection, as well as chronic rejection, etc.

Prevalence of abnormal glucose metabolism and preliminary investigation of its pathogenesis in patients being alive over 3 years after liver transplantation / 中华内分泌代谢杂志

Objective To evaluate the status of abnormal glucose metabolism in patients being alive over 3years after liver transplantation and discuss the possible mechanism of post-transplant diabetes mellitus ( PTDM ).Methods In this study, the clinical data of patients with liver transplantation were collected from April 2001 to December 2008. Patients with diabetes mellitus before operation and those who had died and failed to appear during follow-up were exluded. 199 patients living over 3 years after liver transplantation were follow-up. The prevalence of PTDM was evaluated according to fasting plasma glucose(FPG). Among those without diabetes according to FPG,32patients underwent 75 g oral glucose tolerance test (OGTT) , and fasting and 2 h plasma glucose and insulin were determined. 32 patients were divided into three groups [normal, impaired glucose regulation ( IGR ) , and PTDM groups], proportion of PTDM and homeostasis model assessment ( HOMA ) index were calculated. Results In patients alive over 3 years after liver transplantation, the prevalence of PTDM was 34.67% according to FPG. The OGTT result showed that the proportion of PTDM was 9.38%, IGR, including impaired fasting glucose(IFG) and impaired glucose tolerance ( IGT ) , was 56. 25% , while 34. 37% remained normal. The homeostasis model assessment β cell function index( HOMA-β ) decreased progressively from normal group, IGR group to PTDM group,and that in PTDM group was significantly lower than those in normal and IGR group( P＜0.01 ). IGR group had the highest homeostasis model assessment for insulin resistance (HOMA-IR) and PTDM group the next, and HOMA-IR in IGR group was significantly higher than normal group. Conclusion In patients alive over 3 years after liver transplantation, the prevalence of PTDM reached 44.05%. Insulin resistance existed during early period of impaired glucose regulation, while the degeneration of β cell progressed with the worsening of impaired glucose regulation.

Long-term Outcomes of Post-transplant Diabetes Mellitus in Renal Transplant Recipients / 대한이식학회지

PURPOSE: Post-transplant diabetes mellitus (PTDM) is believed to cause serious complications. PTDM might be one of the important risk factors of cardiovascular death after renal transplantation. Because the consequence of PTDM is expected to take long time, long-term follow-up is necessary. We performed this study not only to define the prevalence and risk factors of PTDM but also to define the long-term clinical impact of PTDM. METHODS: Among 508 patients who had received renal transplantation at Seoul National University Hospital between July 1969 and December 1995, 431 patients were included. Patients were grouped into PTDM and non-DM groups. The clinical characteristics were compared between two groups. RESULTS: Mean follow-up duration was 121.9 months (2~346 months). PTDM was developed in 68 (15.8%) patients. Recipient age at transplantation (P=0.004), family history of DM (P=0.000) and obesity (P= 0.000) were significant risk factors in multivariate analysis. Complications of PTDM such as cerebrovascular disease (CVD, P=0.040), ischemic heart disease (IHD, P=0.040), and infection (p=0.044) were significantly more frequent in PTDM group. The frequency of chronic allograft nephropathy (CAN) was not different between two groups. Although graft survival rate was not affected by PTDM, patient survival rate was significantly lower in PTDM group (P=0.002). CONCLUSION: PTDM increased complication rates such as CVD, IHD and infection. PTDM seemed not to affect graft survival, but to worsen the patient survival rate.

Risk Factors and Clinical Characteristics of Post-Renal Transplant Diabetes Mellitus / 대한신장학회잡지

To investigate the risk factors and clinical characteristics of postrenal transplant diabetes mellitus (PTDM), we reviewed the records of 177 renal allograft recipients in Maryknoll Hospiatal whose allografts had functioned longer than 6 months. Nineteen patients (10.7%) developed PTDM at 5.0+/-7.8 (1-52) months; 9 (47%) of these within 1 month. PTDM patients were older than nondiabetic renal transplants (42+/-2 vs 37+/-1 years, P<0.05). Body mass index tended to be higher in PTDM (23.5+/-1.0 vs 21.8+/-0.3kg/m2, P=0.09). Number of acute rejections (0.6+/-0.2 vs 0.5+/-0.1) and serum creatinine at 1 year after transplantation (1.2+/-0.8 vs 1.3+/-0.3mg/dL) were not different. Fasting (103.6+/-10.4 vs 84.4+/-1.6mg/dL, P<0.05) and postprandial (189.2+/-24.8 vs 118.6+/-2.3 mg/dL, P<0.01) blood sugars, measured before transplantation, were higher in PTDM. CsA blood level at 1 month posttransplantation was higher in PTDM (350+/-34 vs 279+/-8ng/mL, P<0.05). Fasting serum insulin was significantly higher (28.2+/-12.2 vs 7.3+/-2.0 microunit/dL, P<0.05) and serum C-peptide tended to be higher in PTDM patients compared with euglycemic renal recipients (6.3+/-1.6 vs 3.8+/-0.9ng/dL, P=0.08). All the PTDM patients were treated by either insulin or oral agent; 15 of 19 required no treatment after 4.7+/-6.9 months. In conclusion, prevalence of PTDM was 10.7%. PTDM patients were older. Body mass index was tended to be higher. Fasting and postprandial blood sugars, measured before transplantation, were higher in PTDM. Faslting serum insulin was higher and C-peptide tended to be higher in diabetics. These results suggested that increased insulin resistance plays a major role in the pathogenesis of PTDM.

Conversion Effect from Prednisone to Deflazacort in Diabetic Kidney Transplants / 대한신장학회잡지

The blood sugar control has been a significant problem after transplantation. Cyclosporine is partly responsible for post-transplantation diabetes mellitus (PTDM), but steroid has been well known to have diabetogenic effect and mainly responsible for glucose intolerance after transplantation. Deflazacort, a new steroid, has been introduced as a substitute of conventional steroid to prevent glucose intolerance after transplantation. We performed prospective study of deflazacort conversion from conventional steroid in kidney transplant patients with pre-transplantation diabetes mellitus(pre-Tx DM) or PTDM. A total of 82 kidney transplant patients was included for this study. Forty two patients were converted to deflazacort as a conversion group and 40 patients were remained on conventional steroid as a control group. In conversion group, the patients were converted from steroid to deflazacort with ratio of 5:6 in dosage. Nine patients developed severe anorexia with nausea/vomiting and three patients among them went back on steroid within 3 months after conversion(conversion failure 7.1%). After minimal 6 months of follow-up, there was neither episodes of graft dysfunction nor rejection. There was a significant improvement of glucose control in conversion group. In 12 patients(30.8%), more than 50% dose reduction of insulin or oral hypoglycemics requirement was possible. In control group, however, only 2 patients showed greater than 50% of insulin or oral hypoglycemics dose reduction. We could find that deflazacort conversion had a significant impact on blood sugar control in PTDM patients(11/26) but not in pre-Tx DM patients(1/13). In conclusion, conversion to deflazacort in PTDM patients with stable graft function was safe and blood sugar control was readily possible without an increment of risks of rejection and infection. We propose to use deflazacort as a substitute for prednisone in PTDM patients with stable graft function.