心脏移植术后患者新发糖尿病危险因素的Meta分析

目的 系统评价心脏移植术后患者新发糖尿病的危险因素,为临床防治心脏移植术后新发糖尿病提供依据.方法 计算机检索PubMed、Embase、Cochrane、Web of Science、CINAHL、中国知网、万方数据库、中国生物医学文献数据库和维普数据库,检索时间均为建库至2020年9月,收集心脏移植术后新发糖尿病危险因素的观察性研究.由2名研究者提取资料并进行偏倚风险评价,用RevMan5.3软件进行Meta分析.结果 共纳入14项研究9808例研究对象,心脏移植术后新发糖尿病总发病率为20.22％(1983/9808).Meta分析结果显示,不可干预的危险因素有年龄、糖尿病家族史(OR=1.21、2.15,均P<0.01);可干预的危险因素有体重指数、术前空腹血糖、使用他克莫司、使用类固醇、冷缺血时间(OR=1.08～5.13,P≤0.01).结论 心脏移植术后新发糖尿病受较多因素影响,医护人员应识别其危险因素,采取针对性干预措施,提高治疗效果与移植成功率.     

Recent advances in new-onset diabetes mellitus after kidney transplantation

A common challenge in managing kidney transplant recipients (KTR) is post-transplant diabetes mellitus (PTDM) or diabetes mellitus (DM) newly diagnosed after transplantation, in addition to known pre-existing DM. PTDM is an important risk factor for post-transplant cardiovascular (CV) disease, which adversely affects patient survival and quality of life. CV disease in KTR may manifest as ischemic heart disease, heart failure, and/or left ventricular hypertrophy. Available therapies for PTDM include most agents currently used to treat type 2 diabetes. More recently, the use of sodium glucose co-transporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1 RA), and dipeptidyl peptidase 4 inhibitors (DPP4i) has cautiously extended to KTR with PTDM, even though KTR are typically excluded from large general population clinical trials. Initial evidence from observational studies seems to indicate that SGLT2i, GLP-1 RA, and DPP4i may be safe and effective for glycemic control in KTR, but their benefit in reducing CV events in this otherwise high-risk population remains unproven. These newer drugs must still be used with care due to the increased propensity of KTR for intravascular volume depletion and acute kidney injury due to diarrhea and their single-kidney status, pre-existing burden of peripheral vascular disease, urinary tract infections due to immunosuppression and a surgically altered urinary tract, erythrocytosis from calcineurin inhibitors, and reduced kidney function from acute or chronic rejection.     

Adiponectin and risk of new-onset diabetes mellitus after kidney transplantation

BACKGROUND: New-onset diabetes mellitus after transplantation (NODAT) is a severe complication of kidney transplantation (KTx) with negative effects upon patient and graft survival. Several risk factors for NODAT have been described; however, the search for an early predictive marker is ongoing. It has recently been demonstrated that high concentrations of adiponectin (APN), which is an adipocyte-derived peptide with antiinflammatory and insulin-sensitizing properties, protect against future development of type 2 diabetes in healthy individuals. The purpose of this report was to study pretransplant insulin resistance and analyze pretransplant serum leptin and APN levels as independent risk factors for the development of NODAT. METHODS: A total of 68 KTx patients were studied [mean age, 48 +/- 11 years; 70% males; body mass index (BMI), 25 +/- 3 kg/m]; 31 KTx patients with NODAT and 37 KTx patients without NODAT (non-NODAT) with similar age, sex, BMI, immunosuppression, and posttransplant time were studied. All patients received prednisone and calcineurin inhibitors (75% tacrolimus and 25% cyclosporine A), and 76% of patients received mycophenolate mofetil. Family history of diabetes mellitus was recorded. Pretransplant homeostasis model assessment for insulin resistance (HOMA-IR) index was calculated from fasting plasma glucose and insulin. Pretransplant serum leptin and APN levels were determined by radioimmunoassay. RESULTS: NODAT patients showed higher pretransplant plasma insulin concentrations [NODAT, 13.4 (11-22.7) microIU/mL; non-NODAT, 10.05 (7.45-18.4) microIU/mL; P=0.049], HOMA-IR index [NODAT, 4.18 (2.49-5.75); non-NODAT, 2.63 (1.52-4.68); P=0.043], and lower pretransplant serum APN concentration [NODAT, 8.78 (7.2-11.38) microg/mL; non-NODAT, 11.4 (8.56-15.27) microg/mL, P=0.012]. Inverse correlations between APN and BMI (r=-0.33; P=0.014) and APN and HOMA-IR index (r=-0.39; P=0.002) and between APN and NODAT (r=-0.31; P=0.011) were observed. Multiple logistic regression analysis showed the patients with lower pretransplant APN concentrations to be those at greater risk of developing NODAT [Odds Ratio=0.832 (0.71-0.96); P=0.01]. CONCLUSION: Pretransplant serum APN concentration is an independent predictive factor for NODAT development in kidney-transplanted patients.     

肾移植术后新发糖尿病危险因素分析

目的 探讨肾移植术后新发糖尿病(new-onset diabetes mellitus after renal transplantation,NODAT)的危险因素.方法 术前未患糖尿病接受同种尸体肾移植的患者706例,根据入选时有否NODAT分为NODAT组和非NODAT组.统计NODAT发生率,对两组患者可能存在...     

Risk factors for development of new-onset diabetes mellitus after transplant in adult lung transplant recipients

The objectives of this study are to examine the incidence of new-onset diabetes mellitus after transplant (NODAT) and to identify its risk factors in adult lung transplant recipients using the Organ Procurement and Transplant Network/United Network of Organ Sharing database. Between July 2004 and December 2007, a total of 3540 adults (≥18 yr old) received their first single- or double-lung transplant alone and had at least one follow-up report of post-transplant diabetic status. Among these, 2991 recipients were identified as not having diabetes mellitus (DM) pre-transplant. Risk factors for NODAT were examined. DM was newly reported in 33.4% of the 2991 recipients over the median follow-up time of 670 d. Significant independent risk factors for the development of NODAT included male gender (HR = 1.15), recipient age ≥50 (1.46), African American (1.39), higher body mass index (1.51 for ≥30 vs. 18-25), cystic fibrosis (3.30), and tacrolimus use at discharge (1.67). NODAT occurred in a third of adult lung transplant recipients during the median follow-up period. Some of the risk factors for NODAT after lung transplant are similar to those reported in other solid-organ transplants. Cystic fibrosis is a strong risk factor for development of NODAT after lung transplant.     

Incidence and risk factors of new-onset diabetes mellitus after renal transplantation

PURPOSE: New-onset diabetes mellitus (PTDM), a major metabolic complication after renal transplantation, examined for incidence and risk factors. METHODS: The records of 358 renal transplant recipients with functioning grafts, from 1986 to 2006, were categorized into two groups according to the usage of tacrolimus (FK): FK-based (n = 120 patients) and non-FK-based (n = 238). Using Kaplan-Meier survival analysis and a Cox regression model, this study analyzed the cumulative incidence of PTDM and risk factors, including gender, age, and presence of hepatitis. RESULTS: Cumulative incidences of PTDM after 1, 3, and 5 years posttransplantation in the FK-based group were 11%, 18%, and 22%, respectively. In the non-FK-based group, the cumulative incidences were 5%, 9%, and 12% (P = .01). Taking into account the risk factors, the cumulative incidence of PTDM was significant among patients 51 years or older (odds ratio, 3.965; P = .005), but not with regard to gender or presence of hepatitis B and/or C. Overall cumulative incidence of PTDM in our series was 15% (54/358), including 44% (24/54) of cases that occurred within 1 year after renal transplantation. CONCLUSION: FK is more diabetogenic than cyclosporine or sirolimus. Older age (>==51 years) is a significant risk factor, in contrast to hepatitis and gender. About half of these cases of PTDM occurred within 1 year after transplantation. These results suggest that aggressive monitoring of blood sugar is necessary for early detection of PTDM.     

肾移植术后新发糖尿病危险因素研究现状

综述肾移植术后新发糖尿病的定义及诊断标准、肾移植术后新发糖尿病发病率和危险因素,为临床医护工作者更好地了解该疾病及预防肾移植术后糖尿病的发生提供参考。     

The burden of new-onset diabetes mellitus after transplantation

The clinical impact of new-onset diabetes mellitus (NODM) is frequently underestimated by clinicians. NODM occurs in approximately 15-20% of renal transplant patients and 15% of liver transplant recipients. Diabetes after transplantation is a leading risk factor for cardiovascular events, with a higher prognostic value than in the non-transplant population. NODM also appears to have a negative influence on graft function, and graft survival rates after renal transplantation are significantly lower in patients who develop diabetes than in controls. Patient mortality following renal transplantation is generally found to be higher in patients with NODM, due to increased cardiovascular and peripheral vascular disease, accelerated graft deterioration and diabetes-related complications, notably infection. A renal registry analysis has reported an increase of 87% in risk of death following onset of NODM. There is also limited evidence that NODM is associated with increased risk of death in liver transplant patients. The relative incidence and severity of diabetic complications in transplant recipients have not been assessed rigorously in a clinical trial but registry data indicate that 20% of renal transplant patients with NODM experience at least one clinically significant diabetic complication within three years. Financially, the additional healthcare costs incurred over the first two years following onset of NODM amount to 21,500 dollars. Routine pre-transplant assessment of diabetic risk, with requisite modification of lifestyle, glycaemic monitoring and immunosuppressive regimens, and coupled with standardized, aggressive hypoglycaemic management as necessary, offers an important opportunity to alleviate the burden of NODM for transplant patients.     

Renal resistive index as a new independent risk factor for new-onset diabetes mellitus after kidney transplantation

Pulse pressure and urinary albumin excretion were recently identified as risk factors of new-onset diabetes after renal transplantation (NODAT), suggesting that microvascular injury may be implicated in NODAT. However, the relationship between of microvascular injury and NODAT is unknown. In the present long-term (median follow-up: 5.7years; observation period: 4908 patient-years) retrospective study in 656 renal transplant recipients, the association between baseline renal resistance index (RI, used as a marker of widespread microvascular damage) and the incidence of NODAT was assessed. The incidence of NODAT was 11.2% and 14.6% at 5 and 10years, respectively, after transplantation. RI at 3months was a risk factor for NODAT [hazard ratio (HR) per 0.1: 2.19 (1.55-3.09), P<0.0001]. RI >0.75 (vs. 0≤0.75) was a potent a predictor of NODAT [HR: 3.29 (1.91-5.67), P<0.0001], even after adjustments [HR: 3.29 (1.50-7.24), P=0.0030] on age, weight, glucose, nephropathy, and arterial pressure. Similar results were observed when RI was measured at 1month [HR per 0.1:1.74 (1.33-2.27), P<0.0001] and 12months [HR per 0.1:1.74 (1.33-2.27), P<0.0001] after transplantation. High RI early after renal transplantation is a long-term risk factor for NODAT, and could be used to refine the individual risk of NODAT.     

Immunosuppressive medications, clinical and metabolic parameters in new-onset diabetes mellitus after kidney transplantation.

New-onset diabetes after transplantation (NODAT) is a growing concern in transplantation. All modifiable risk factors are not yet identified. We assessed the relationship between baseline clinical and biochemical parameters and NODAT. Eight-hundred and fifty-seven in-Caucasian renal transplant recipients were included. Charts were individually reviewed. The follow-up was 5.3 years (ranges: 0.25-20.8; 5613 patient-years). The incidence of NODAT was 15.0%, 18.4% and 22.0% at 10, 15 and 20 years following transplantation. Age, body mass index (BMI), glucose (all P < 0.0001) and triglycerides [hazard ratio (HR) per 1 mmol/l: 1.44 [1.17-1.77], P = 0.0006] were potent risk factors whereas steroid withdrawal (HR: 0.69 [0.47-1.01], P = 0.0601) reduced the risk. As compared to cyclosporine, sirolimus (HR: 3.26 [1.63-6.49], P = 0.0008) and tacrolimus (HR: 3.04 [2.02-4.59], P < 0.0001) were risk factors for NODAT. The risk of NODAT was comparable for sirolimus (HR: 2.35 [1.06-5.19], P = 0.0350) and tacrolimus (HR: 2.34 [1.46-3.75], P = 0.0004) after adjustments on age, BMI, glucose and steroid withdrawal; however, unlike sirolimus, tacrolimus remained significant after adjustment on triglycerides. The risk of NODAT appeared similar, but its pathophysiology seemed different in sirolimus- and tacrolimus-treated patients; this observation needs confirmation. However, main independent risk factors were age, BMI, initial glucose and triglycerides.     

Risk factors for the development of new-onset diabetes mellitus in a living related renal transplant program

New-onset diabetes mellitus is associated with considerable morbidity after transplantation. We evaluated 78 living related renal transplant recipients due to all causes except diabetic nephropathy a waiting a living related renal transplantation. We evaluated demographic characteristics, pretransplant glycemic profile, fasting C-peptide levels, plasma insulin levels, pretransplant insulin resistance, and immunosuppression protocols. Among the 16.7% of patients developing diabetes mellitus at the end of 1 year, age, family history, and impaired glucose tolerance at the time of transplantation corelated with the development of diabetes mellitus in the posttransplant period.     

原位异体肝移植术后新发慢性肾脏病的危险因素和预后分析

目的:探索术前估测肾小球滤过率（estimated glomerular filtration rate, eGFR）正常的成年人肝移植术后新发慢性肾脏病（new-onset chronic kidney disease, NOCKD）的围手术期危险因素,为NOCKD高危人群的筛查提供早期预测模型。方法:采用回顾性病例...     

Polycystic kidney disease is a risk factor for new-onset diabetes after transplantation

BACKGROUND: Data from matched historical cohort studies suggest that autosomal-dominant polycystic kidney disease (ADPKD) may be a risk factor for new-onset diabetes after transplantation (NODAT). METHOD: A retrospective study of 429 renal allografts transplanted from 1990 through 2004 in nondiabetic patients was performed. A multivariate analysis of risk factors for NODAT was performed with focus on ADPKD. RESULTS: A total of 6.5% of all patients developed NODAT and a further 11% developed impaired glucose tolerance. NODAT developed in 13.4% of patients with ADPKD compared with 5.2% of non-ADPKD patients (P=0.01). There were significant univariate associations between NODAT and recipient age (P=0.001) and weight (P<0.0001). There was no association between NODAT and recipient gender, human leukocyte antigen mismatch, acute rejection, or cumulative methylprednisolone dose. In a multivariate analysis, ADPKD was a strong risk factor for the development of NODAT (odds ratio [OR]=2.41, P=0.035) after correction for recipient age, weight, gender, ethnicity, and tacrolimus use. Age (OR=1.06), weight (OR=1.04), and nonwhite race (OR=5.04) were the other significant variables. CONCLUSION: We conclude that ADPKD is a significant risk factor for the development of NODAT. This may influence the follow up and management choices of these patients in the future.     

影响肝移植术后新发糖尿病逆转的相关因素

目的 探讨影响肝移植术后新发糖尿病(PTDM)逆转的相关因素.方法 回顾分析232例肝移植受者的临床资料,术后共有62例患者发生PTDM,发生率为26.7%.根据PTDM是否发生逆转,将62例患者分为暂时性PTDM组(34例)和持续性PTDM组(28例).对两组患者的性别、年龄、体重指数、糖尿病家族史、乙型肝炎病毒感染情况、术前空腹血糖水平、免疫抑制剂使用及其血药浓度、皮质激素的使用时间等相关因素进行分析.结果 两组间患者的性别、体重指数、糖尿病家族史、术前空腹血糖水平、免疫抑制方案中皮质激素的持续使用时间、术后血他克莫司浓度及使用环孢素A的患者比例等因素的差异均无统计学意义(P＞0.05).与持续性PTDM组相比,暂时性PTDM组患者移植时年龄较轻,分别为(54±8)岁和(42±6)岁(P＜0.05);发生PTDM的术后时间较晚,分别为术后(18±23)d和(35±42)d(P＜0.05);免疫抑制方案中联合运用吗替麦考酚酯(MMF)或西罗莫司(SRL)的患者比例较高,分别为0和8.9%(P＜0.05).经多因素Logistic回归分析显示,只有移植时年龄是PTDM逆转的独立预测因子(比值比为1.312,95%可信区间为1.005～1.743).结论 患者移植时年龄、发生PTDM时的术后时间及免疫抑制方案中使用MMF或SRL的患者比例等因素与肝移植术后PTDM逆转相关,但只有移植时年龄是PTDM逆转的独立预测因子.

Abstract：

Objective To study the related factors associated with the reversal of posttransplant diabetes mellitus (PTDM) following liver transplantation. Methods The clinical data of 62patients with PTDM in 232 patients receiving liver transplantation (26. 7 %) were retrospectively analyzed and the patients were divided into two groups: patients with transient PTDM (34 cases) and those with persistent PTDM (28 cases). Pre-operative and post-operative variables, including sex,age, body mass index, family history of diabetes, hepatitis B virus infection, pretransplantation fasting plasma glucose, the immunosuppressant regime, FK506 concentration and duration of steroid usage, were analyzed retrospectively. Results The variables, including sex, age, body mass index,family history of diabetes, hepatitis B virus infection, pretransplantation fasting plasma glucose,FK506 concentration at month 1, 3 and 6 after operation, rate of cyclosporine usage and duration of steroid usage had no significant difference between the two groups (P＞0. 05). Compared with the persistent PTDM patients, the transient PTDM patients were characterized by younger age at the time of transplantation (54 ± 8 vs. 42 ± 6 years, P＜0. 05), longer time before the development of PTDM (18 ± 23 vs. 35 ± 42 days, P＜0. 05), and higher rate of mycophenolate mofetil or sirolimus usage (0vs. 8. 9 %, P＜0. 05). Based on a multivariate analysis, age at the time of transplantation was determined as the single independent predictive factor associated with reversal of PTDM following liver transplantation (odds ratio: 1. 312, 95 % confidence interval: 1. 005 - 1. 743). Conclusion Age at the time of transplantation, duration before the development of PTDM and rate of mycophenolate mofetil or sirolimus usage are associated with reversal of PTDM following liver transplantation. Among these factors, age at the time of transplantation is only the single independent predictive factor.     

Outcome of patients with new-onset diabetes mellitus after liver transplantation compared with those without diabetes mellitus

In liver transplant recipients, new onset of diabetes mellitus (posttransplant diabetes mellitus or PTDM) is estimated to occur in 9% to 21% of recipients. The limited published data on survival and posttransplant complications in liver transplant recipients who develop PTDM show conflicting results. The objective of our study was to compare the morbidity and mortality of 46 patients who developed PTDM with 92 age- and sex-matched patients without pretransplant or posttransplant diabetes mellitus (DM). The demographics of both groups were similar except that there were more blacks with PTDM. The incidence of following complications was higher in the PTDM group compared with the control group: cardiac (48% v 24%; P = .005), major infections (41% v 25%; P = .07), minor infections (28% v 5%; P = .001), neurologic (22% v 9%; P = .05), and neuropsychiatric (22% v 6%; P = .009). Acute rejection was seen more commonly in the PTDM group (50% v 30%; P = .03). The duration of hospital stay, cost of hospitalization, retransplantation rate, and graft survival were similar in both groups. Patient survival also was similar in the PTDM and control groups at 1 year (93.5% v 83.5%), two years (88.1% v 77.9%), and 5 years (75% v 77.2%); Kaplan-Meier survival analysis also did not show survival difference. In conclusion, PTDM was associated with significant morbidity, and our findings suggest that patients with PTDM should be monitored very closely to improve long-term outcome. (Liver Transpl 2002;8:708-713.)     

影响肝移植术后新发糖尿病逆转的相关因素

Objective To study the related factors associated with the reversal of posttransplant diabetes mellitus (PTDM) following liver transplantation. Methods The clinical data of 62patients with PTDM in 232 patients receiving liver transplantation (26. 7 %) were retrospectively analyzed and the patients were divided into two groups: patients with transient PTDM (34 cases) and those with persistent PTDM (28 cases). Pre-operative and post-operative variables, including sex,age, body mass index, family history of diabetes, hepatitis B virus infection, pretransplantation fasting plasma glucose, the immunosuppressant regime, FK506 concentration and duration of steroid usage, were analyzed retrospectively. Results The variables, including sex, age, body mass index,family history of diabetes, hepatitis B virus infection, pretransplantation fasting plasma glucose,FK506 concentration at month 1, 3 and 6 after operation, rate of cyclosporine usage and duration of steroid usage had no significant difference between the two groups (P＞0. 05). Compared with the persistent PTDM patients, the transient PTDM patients were characterized by younger age at the time of transplantation (54 ± 8 vs. 42 ± 6 years, P＜0. 05), longer time before the development of PTDM (18 ± 23 vs. 35 ± 42 days, P＜0. 05), and higher rate of mycophenolate mofetil or sirolimus usage (0vs. 8. 9 %, P＜0. 05). Based on a multivariate analysis, age at the time of transplantation was determined as the single independent predictive factor associated with reversal of PTDM following liver transplantation (odds ratio: 1. 312, 95 % confidence interval: 1. 005 - 1. 743). Conclusion Age at the time of transplantation, duration before the development of PTDM and rate of mycophenolate mofetil or sirolimus usage are associated with reversal of PTDM following liver transplantation. Among these factors, age at the time of transplantation is only the single independent predictive factor.     

影响肝移植术后新发糖尿病逆转的相关因素

Objective To study the related factors associated with the reversal of posttransplant diabetes mellitus (PTDM) following liver transplantation. Methods The clinical data of 62patients with PTDM in 232 patients receiving liver transplantation (26. 7 %) were retrospectively analyzed and the patients were divided into two groups: patients with transient PTDM (34 cases) and those with persistent PTDM (28 cases). Pre-operative and post-operative variables, including sex,age, body mass index, family history of diabetes, hepatitis B virus infection, pretransplantation fasting plasma glucose, the immunosuppressant regime, FK506 concentration and duration of steroid usage, were analyzed retrospectively. Results The variables, including sex, age, body mass index,family history of diabetes, hepatitis B virus infection, pretransplantation fasting plasma glucose,FK506 concentration at month 1, 3 and 6 after operation, rate of cyclosporine usage and duration of steroid usage had no significant difference between the two groups (P＞0. 05). Compared with the persistent PTDM patients, the transient PTDM patients were characterized by younger age at the time of transplantation (54 ± 8 vs. 42 ± 6 years, P＜0. 05), longer time before the development of PTDM (18 ± 23 vs. 35 ± 42 days, P＜0. 05), and higher rate of mycophenolate mofetil or sirolimus usage (0vs. 8. 9 %, P＜0. 05). Based on a multivariate analysis, age at the time of transplantation was determined as the single independent predictive factor associated with reversal of PTDM following liver transplantation (odds ratio: 1. 312, 95 % confidence interval: 1. 005 - 1. 743). Conclusion Age at the time of transplantation, duration before the development of PTDM and rate of mycophenolate mofetil or sirolimus usage are associated with reversal of PTDM following liver transplantation. Among these factors, age at the time of transplantation is only the single independent predictive factor.     

影响肝移植术后新发糖尿病逆转的相关因素

Objective To study the related factors associated with the reversal of posttransplant diabetes mellitus (PTDM) following liver transplantation. Methods The clinical data of 62patients with PTDM in 232 patients receiving liver transplantation (26. 7 %) were retrospectively analyzed and the patients were divided into two groups: patients with transient PTDM (34 cases) and those with persistent PTDM (28 cases). Pre-operative and post-operative variables, including sex,age, body mass index, family history of diabetes, hepatitis B virus infection, pretransplantation fasting plasma glucose, the immunosuppressant regime, FK506 concentration and duration of steroid usage, were analyzed retrospectively. Results The variables, including sex, age, body mass index,family history of diabetes, hepatitis B virus infection, pretransplantation fasting plasma glucose,FK506 concentration at month 1, 3 and 6 after operation, rate of cyclosporine usage and duration of steroid usage had no significant difference between the two groups (P＞0. 05). Compared with the persistent PTDM patients, the transient PTDM patients were characterized by younger age at the time of transplantation (54 ± 8 vs. 42 ± 6 years, P＜0. 05), longer time before the development of PTDM (18 ± 23 vs. 35 ± 42 days, P＜0. 05), and higher rate of mycophenolate mofetil or sirolimus usage (0vs. 8. 9 %, P＜0. 05). Based on a multivariate analysis, age at the time of transplantation was determined as the single independent predictive factor associated with reversal of PTDM following liver transplantation (odds ratio: 1. 312, 95 % confidence interval: 1. 005 - 1. 743). Conclusion Age at the time of transplantation, duration before the development of PTDM and rate of mycophenolate mofetil or sirolimus usage are associated with reversal of PTDM following liver transplantation. Among these factors, age at the time of transplantation is only the single independent predictive factor.