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Solid organ transplantation has significantly prolonged the survival of patients with end-stage diseases. However, long-term use of immunosuppressants will increase the risk of post-transplantation diabetes mellitus (PTDM) in the recipients, thereby elevating the risk of infection, cardiovascular disease and death. In recent years, with persistent improvement of diagnostic criteria of PTDM, clinicians have deepened the understanding of this disease. Compared with type 2 diabetes mellitus, PTDM significantly differs in pathophysiological characteristics and clinical progression. Hence, different treatment strategies should be adopted. Early identification of risk factors of organ transplant recipients, early diagnosis and intervention are of significance for improving the quality of life of recipients, prolonging the survival of grafts and reducing the fatality of recipients. Therefore, the diagnosis, incidence and risk factors of PTDM were reviewed in this article, aiming to provide reference for clinicians to deliver prompt diagnosis and intervention for PTDM.
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Diabetes mellitus is one of the most common complications after liver transplantation. The survival rate of recipients after liver transplantation with diabetes mellitus and the long-term survival rate of grafts are significantly lower than those of their counterparts without diabetes mellitus. In recent years, diabetes mellitus after liver transplantation has attracted widespread attention along with the rapid development of liver transplantation in China. Although post-transplantation diabetes mellitus (PTDM) has been extensively investigated in the past two decades, multiple problems remain to be further resolved. The study was designed to review the latest research progress upon diabetes mellitus after liver transplantation, covering the definition and diagnostic criteria of PTDM, risk factors, prevention and treatment of diabetes mellitus after liver transplantation, aiming to deepen the understanding of diabetes mellitus following liver transplantation, deliver effective prevention and management, improve the long-term survival rate and enhance the quality of life of the recipients.
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Objective To analyze the risk factors for the occurrence of post transplantation diabetes mellitus (PTDM) in renal transplant recipients, establish a prediction model for PTDM and evaluate its prediction value. Methods Clinical data of 915 renal transplant recipients were retrospectively analyzed. According to the occurrence of PTDM, all recipients were divided into the PTDM group (n=78) and non-PTDM group (n=837). The main indexes of recipients were collected. The risk factors for the occurrence of PTDM in renal transplant recipients were analyzed by univariate and multivariate analysis. The prediction model for PTDM was established and its prediction value was evaluated. Results Family history of diabetes mellitus, body mass index (BMI), preoperative 2 h postprandial blood glucose and preoperative glycosylated hemoglobin were the independent risk factors for the occurrence of PTDM in renal transplant recipients. The prediction model for PTDM was logit (P)=2.199×family history of diabetes (yes=1, no=0)+0.109×BMI+0.151×2 h postprandial blood glucose (mmol/L)+0.508×glycosylated hemoglobin (%)-9.123. The results of receiver operating characteristic (ROC) curve showed that the area under the curve (AUC) of these 4 predictors combined for predicting PTDM in renal transplant recipients was 0.830 [95% confidence interval (CI) 0.786-0.873], the cut-off value was 0.0608, the sensitivity was 0.821, the specificity was 0.700, and the Youden index was 0.521 (P < 0.05). Conclusions Family history of diabetes mellitus, BMI, preoperative 2 h postprandial blood glucose and preoperative glycosylated hemoglobin are the independent risk factors for the occurrence of PTDM in renal transplant recipients. The prediction model for PTDM combined with4 predictors yield relatively high prediction value for PTDM.
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Objective To observe of the effects of tacrolimus on blood glucose,insulin secretion and the expression of phosphorylated AKT in rats in order to study the mechanism of diabetogenic effects of tacrolimus.Methods 40 male SD rats were randomly divided into two groups.The rats in tacrolimus group were delivered tacrolimus at a dose of 4mg/kg· d.The rats in the control group were given the same amount of saline solution in the same way.The body weights,fasting blood glucose levels and blood concentrations of tacrolimus were measured monthly.After 5 months,all rats were killed.Pancreas and liver tissue were stored in 4％ paraformaldehyde solution.Serum insulin levels were detected by radioimmunoassay method.The expression of phosphorylated AKT in liver were measured by immunohisto-chemical method.Results ①The body weights in tacrolimus group in the 3rd,4th,and 5th month were significantly lower than those in the control group (P＜0.01).②The blood glucose levels in tacrolimus group in the 3rd,4th,and 5th month were significantly higher than those in the control group (P＜0.05).③The insulin secretion and insulin sensitivity index in tacrolimus group were significantly lower than those in the control group (P＜0.01).④The rats in tacrolimus group showed varying degrees of damage in pancreatic duct and pancreatic islet cells.⑤The expression of phosphorylated AKT in liver cells in tacrolimus group were significantly lower than those in the control group (P＜0.05).Conclusions Tacrolimus can induce pancreatic islet cells necrosis,decrease the number of islet cells,reduce insulin secretion and insulin sensitivity,which lead to blood hyperglycemia in rats.In addition,we also find that tacrolimus can reduce expression of phosphorylated AKT in hepatic tissue,which indicates that tacrolimus results insulin resistance through interfering PI3K/ AKT signal transduction pathways.
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Objective To systematically review the predictive factors associated with reversibility of post-transplantation diabetes mellitus in adults using Meta-analysis,and to provide a theoretical basis for clinical prevention and treatment of diabetes after transplantation.Methods Pub Med,Web of Science,Cochrane Library (Issue 5,2017),CNKI,VIP and WanFang Data were searched from inception until May 2017.Two authors independently assessed the trials for inclusion and extracted the data.Discrepancies were resolved in consultation with a third reviewer.Publication biases were evaluated,and the Meta-analyses were conducted with RevMan5.3.Results A total of 7 studies were analyzed which involved 979 adults.Metaanalysis showed the following significant predictive factors:male (OR =1.73,95％ CI 1.19 to 2.50,P ＜0.05),advanced age (MD =1.73,95％ CI 0.07 to 10.39,P =0.05),high FPG before transplantation (MD=5.66,95％CI 0.11 to 11.31,P=0.05),hepatitis C virus (HCV) infection (OR=1.52,95％CI 1.08 to 2.14,P ＜ 0.05),high frequency of combination therapy with MMF (OR =0.26,95％ CI 0.11 to 0.61,P ＜ 0.05),and short time before development of PTDM (MD =-19.08,95％ CI-37.08 to -1.07,P ＜ 0.05).There was no correlation with preoperative BMI,family history of diabetes and acute rejection.Conclusion The study showed that male,advanced age,high FPG before transplantation,hepatitis C virus infection,high frequency combination therapy with MMF,short time before development of posttransplantation diabetes mellitus were the predictive factors associated with reversibility of post-transplantation diabetes mellitus.
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Objective To observe the effects of tacrolimus on blood glucose, insulin, expressions of protein phos-phatase 2A and P-AKT in rats in order to explore the mechanism of hyperglycemic action of tacrolimus. Methods Sixty male SD rats (body weight 89. 83 ±4. 44 g) were randomly divided into tacrolimus group (n =40) and control group (n=20). The rats in the tacrolimus group were administrated with tacrolimus 4 mg/kg daily. The rats in the control group were given the same amount of normal drinking water daily. The rat body weight, fasting blood glucose concentration and blood concentration of tacrolimus were measured monthly. All rats were killed at 5 months after the tacrolimus administra-tion. The serum insulin levels were detected by radioimmunoassay method. The expressions of PP2A and P-AKT in liver tissues were assessed by immunohistochemistry. Results After two months of administration, the blood glucose levels in the tacrolimus group were significantly higher than those in the control group. The HOMA-IR in tacrolimus group was signif- icantly higher than that in the control group P<0. 05 ) . ISI was significantly lower than that in the control group ( P<0. 05). Immunohistochemical examination showed that the expression of PP2A in hepatocytes in the tacrolimus group was increased compared with the control group, while expression of P-AKT in hepatocytes of the tacrolimus group was decreased than that in the control group. Conclusions Tacrolimus can induce necrosis of islet cells, decrease of the amount of islet cells and insulin secretion, decease of sensitivity to insulin, and increase the resistance to insulin, therefore, leading to in-crease the blood glucose level in rats. The expression of PP2A in hepatocytes in the tacrolimus group is increased, while the expression of P-AKT is decreased. Interfering of insulin signal transduction pathways may be involved in the hyperglyce-mic effects of tacrolimus.
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Objective To observe the effects of cyclosporin A on the expression of phosphorylated AKT in hepatocytes, and to investigate the mechanism of insulin resistance caused by cyclosporin A. Methods This study included two parts. 1. In vitro experiment:Human hepatocyte HL77022 cell line was cultured at different concentrations of cyclosporin A (0?1 μmol/L, 1 μmol/L, 5 μmol/L) for 48 hours. The expressions of phosphorylated AKT ( P?AKT) in HL77022 cells were measured by Western blot assay. 2. Rat in vivo experiment: SD rats were randomly divided into 2 groups. The rats in the control group were administrated with distilled water 1 mL/Kg/d. The rats in the cyclosporine group were administrated with cyclosporine 25 mg/Kg/d. The total experiment time was 5 months. The levels of fasting blood glucose and insulin were tested at the end of the experiment. The insulin resistance index and insulin sensitivity index were calculated. The expression of P?AKT in the rat hepatocytes was measured by immunohistochemistry. Results 1. Each group of the HL7702 cells treated by CsA ( 0?1 μmol/L, 1 μmol/L, 5 μmol/L ) showed a significantly decreased expression of P?AKT (P<0?05, P<0?01, and P<0?01). 2. After 5 months of therapy, the fasting blood glucose level of rats in the cyclosporine group was 9?28 mmol/L, indicating that cyclosporine?induced diabetic rat models were established. The insulin sensitivity index in the cyclosporine group was lower than that in the control group ( P<0?05 ) . The expression of P?AKT in liver in the cyclosporine group was significantly lower than that in the control group ( P <0?05) . Conclusions Therapeutic dose of cyclosporine has hyperglycemic effects on rats. Cyclosporine can reduce the expression of phosphorylated AKT in hepatic tissue in rats and also decrease the expression of P?AKT in human hepatocyte HL77022 cells, which indicate that cyclosporine may cause insulin resistance by interfering PI3K/AKT signal transduction pathway.
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Objective Glucose metabolism trend was dynamicly mornitored following liver transplantation, and its affecting factors were assessed. Methods The glucose metabolism status were assessed at four time points respectively after liver transplants, then they were divided into two groups:normal glucose metabolism (NGM) and abnormal glucose metabolism (AGM). The clinical data were univariate analyzed and multivariate analyzed to screen the risk factors. Results At 1 month, 3 months, 1 year and 3 years post-transplantation, the incidence of AGM were 74.0%, 43.9%, 29.4%, 24.1% respectively Between these two groups, age > 45 y had a significant difference at 1 month, 3 months, 1 year and 3years post-transplantation; the use of tacrolimus had a significant difference at 3 months, 1 year and 3years post-transplantation, but the dose of tacrolimus or tacrolimus blood concentration showed no significant difference; high dose of glucocorticoid had significant difference at 1 month , 3 months post-transplantation; high BMI and acute rejection had significant difference at 1 month post-transplantation. Conclusions There is a high incidence of abnormal glucose metabolism (AGM) in the early stage post-transplantation, and a considerable number of patients' glucose metabolism improved in the later period. Age>45 y and tacrolimus affect glucose metabolism for a longer period post-transplants. High BMI and acute rejection have an impact on glucose metabolism only in the early stage post-transplantation. Large dose of glucocorticoid affect glucose metabolism for at least 3 months post-transplantation , and there is no significant difference after 1 year.
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Objective To evaluate the efficacy and safety of glargine combined with repaglinide in the treatment of post-transplantation diabetes mellitus(PTDM).Methods PTDM patients who were treated in our hospital from Jan 1,2010 to Dec 31,2010 were enrolled in this study.They were administrated with glargine combined with repaglinide for 6 months,and their glucose level,hepatic and renal function indicators,and tacrolimus concentration were examined at baseline and 1,3,and 6 months after treatment.Results Totally 44 patients were included and given dietary control.Three cases were not given any hypoglycemic drugs,7 were administrated with glargine only,30 cases received glargine combined with repaglinide therapy,and 4 cases required intensive insulin therapy.All the patients achieved satisfactory glycemic control.The hepatic function,renal function,and serum tacrolimus concentration showed no significant change before and after repaglinide therapy(P ＞ 0.05).Five hypoglycemic events were recorded during the treatment,in which the lowest blood glucose level was 3.7 mmol/L.No severe hypoglycemia happened.Conclusion On the basis of dietary control,glargine combined with repaglinide provides a safe and effective therapy for PTDM.
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La diabetes mellitus postrasplante renal resulta frecuente, precoz, multifactorial y de singular importancia; está vinculada a la aparición de nefropatía crónica y procesos cardiovasculares, principales causas de mortalidad y pérdida de los injertos. Se realizó esta investigación con 307 pacientes que habían recibido trasplantes renales, se excluyeron los diabéticos antes del implante, los retrasplante y aquellos cuyo injerto no sobrepasara el año de vida, para crear un modelo predictivo que permitiera conocer el porcentaje de posibilidades de desarrollar esta complicación. Se hizo un estudio de cohorte retrospectivo, se consideraron complicaciones pretrasplante, se aplicó un modelo de regresión logística binaria con variables de significación estadística < 0,05 y/o un odds ratio diferente de 1, edad del receptor, antecedentes familiares de diabetes, infección por el virus de hepatitis C, cifras de colesterol, triglicéridos y glucemia pretrasplante. Se confeccionó un programa en sistema Excel, que permitió realizar la predicción. Queda ahora, mediante estudio prospectivo, multicéntrico y mayor número de enfermos, validar esta propuesta.
Renal post-transplantation diabetes mellitus if frequent, early, multifactor, and of a peculiar significance; it is linked to appearance of a chronic nephropathy, and cardiovascular processes, mainly causes of mortality, and graft failure. A total of 307 renal transplantation patients were studied, excluding the diabetic ones before transplantation, the re-transplantation, and those whose graft don't exceed of a year of life to create a predictive model allowing know the possibilities percentage to develop this condition. We made a retrospective cohort study, considering pre-transplantation complications. We applied a binary logistic regression model with a statistic significance < 0, 05 and/or a odds ratio different from 1, recipient age, familiar backgrounds of diabetes, infection from hepatitis C, cholesterol figures, triglycerides, and pre-transplantation glycemia. We create a Excel system program allowing us to made the prediction. Now, it is essential to validate this proposal by means of a prospective, multicenter study including a great number of patients.
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Diabetes Mellitus , Valor Predictivo de las Pruebas , Factores de Riesgo , Trasplante de Riñón/efectos adversosRESUMEN
BACKGROUND: New onset diabetes is a common complication after kidney transplantation. However, the clinical course of post-transplant diabetes mellitus (PTDM) remains unclear. The aim of the present study is to analyze the natural courses and risk factors of PTDM according to the time of onset. METHODS: A total of 216 consecutive kidney transplant recipients were enrolled and patient medical records were investigated retrospectively. PTDM was defined as glucose > or =126mg without previous diabetic history. Patients were classified according to the onset (12 months): early PTDM (E-PTDM) and late PTDM (L-PTDM). RESULTS: PTDM was observed in 34 (17.4%) patients. The number of E-PTDM and L-PTDM patients was 17 and 17. Compared with normoglycemic patients, the PTDM group was older and showed higher pre-transplant HbA1c level. The use of tacrolimus was associated with the development of E-PTDM (OR=4.87, 1.71~13.8 in 95% CI) but not L-PTDM (OR=0.34, 0.04~2.70 in 95% CI) CONCLUSIONS: The development of E-PTDM and L-PTDM may have different risk factors. It will be important to choose different therapeutic strategy according to the onset of PTDM.
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Humanos , Diabetes Mellitus , Glucosa , Riñón , Trasplante de Riñón , Registros Médicos , Estudios Retrospectivos , Factores de Riesgo , Tacrolimus , TrasplantesRESUMEN
Objective:To study the effect of cyclosporin A based triple immunosuppressive therapy on the plasma glucose in renal transplant recipients.Method:680 renal transplant recipients treated with cyclosporine A combined with prednisone and mycophenolate mofefil from Jan.1996 to May 2007 were analysed.Result:The morbidities of impaired fast- ing glucose,impaired glucose tolerance and post-transplantation diabetes mellitus (PTDM) were 3.97%,5.15% and 8.09%,respectively.The daily doses and concentrations of CsA and the daily doses of prednisone in the impaired glucose tolerance group and PTDM group were significantly higher than those in the normal plasma glucose group.Conclusion:The daily doses and concentrations of CsA and the daily doses of prednisone were closely related to the impaired glucose toler- ance and PTDM of renal transplant recipients.
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PURPOSE: The aim of this study was to assess the incidence of post-transplantation diabetes mellitus (PTDM) in renal allograft recipients and investigate the risk factors contributing to the development and progression of PTDM and its underlying pathogenic mechanism(s). METHODS: We analyzed the incidence and risk factors of PTDM after renal transplantation, retrospectively. A total of 913 renal transplant recipients with normal glucose tolerance (NGT) were enrolled. The recipient who needs medical treatment of hyperglycemia more than one month was considered as PTDM patient. We classified PTDM as early PTDM (within post-Tx 1 year) and late PTDM. RESULTS: Two hundred seven cases of PTDM were developed (22.7%) out of 913 patients. The cumulative incidence of PTDM was 9.4%, 20.5% and 29.0% at post-transplantation 1-, 5- and 10 year respectively. In uni-variate and multivariate analysis of PTDM onset, elderly recipients, tacrolimus-based immunosuppressive group and hepatitis B virus carrier group showed significantly higher incidence of PTDM. Among 207 cases of PTDM, early and late PTDM were 85 cases and 122 cases respectively. The late PTDM developed persistently after post-transplant 5 years. In risk factor analysis of early and late PTDM, late PTDM showed different results compared to early PTDM. The clinical conditions that cause larger dose or high level of calcineurin inhibitor (CNI), such as double immunosuppressive regimen group, induction immunosuppressive therapy-free group and unrelated donor transplant group, were a significant independent risk factor of late PTDM. CONCLUSION: Our data showed clinical clues that persistent cumulative CNI exposure was correlated with onset of late PTDM. Careful selection of immunosuppressive regimen in high-risk recipients such as elderly patients and hepatitis B virus carrier may decrease the development of PTDM.
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Anciano , Humanos , Aloinjertos , Calcineurina , Diabetes Mellitus , Glucosa , Virus de la Hepatitis B , Hiperglucemia , Incidencia , Trasplante de Riñón , Análisis Multivariante , Estudios Retrospectivos , Factores de Riesgo , Trasplante , Donante no EmparentadoRESUMEN
PURPOSE: Liver transplantation (LT) can cure abnormality of glucose metabolism, but cause altered glucose metabolism with immunosuppressive treatment. Up to now, almost all studies have been performed in cadaveric donor liver transplantation (CDLT). We underwent study in CDLT and also living donor liver transplantation (LDLT) recipients. METHODS: Among 397 adult-to-adult LT recipients between January 1994 and August 2001, we selected 81 patients who could be followed more than 12 months by using the table of random sampling numbers. We reviewed the change of blood glucose and risk factors, complications and survival retrospectively between post-transplantation diabetes mellitus (PTDM) and no PTDM patients. RESULTS: Clinical data showed 34 : 47 in frequency of PTDM to no PTDM. Age, family history of DM, preoperative DM history over 6 months had a significant risk of PTDM. There was no difference of PTDM frequency between CDLT and LDLT and its subgroup. The worse post-transplant graft function causes the more incidence of PTDM (P=0.051). FK506 had higher relation with PTDM than cyclosporine and mycophenolate mofetile (P=0.058). The incidence of DM after operation has been decreased by 6 months, but thereafter no further. There were 18 of De Novo DM among 34 PTDM patients, and only 1 preoperative DM patient improved after LT. Between PTDM and no PTDM group, there were no significant difference of complication rate and 5-year survival rate. CONCLUSIONS: The types of graft would not affect the incidence of PTDM if the graft function were preserved. Other clinical data showed similar results to previous reports.