Risk factors and consequences of post‐transplant diabetes mellitus

Demirci MS, Toz H, Y?lmaz F, Ertilav M, Asci G, Ozkahya M, Zeytinoglu A, Nart D, Ok E. Risk factors and consequences of post‐transplant diabetes mellitus.
Clin Transplant 2010 DOI: 10.1111/j.1399‐0012.2010.01247.x.
© 2010 John Wiley & Sons A/S. Abstract: Background: The aim of this study is to investigate the clinical course as well as risk factors and prognosis of post‐transplant diabetes mellitus (PTDM). Methods: Five hundred fifty‐five kidney transplant recipients were retrospectively evaluated. PTDM was defined as fasting blood glucose ≥140 mg/dL on at least two consecutive measurements or requirement of oral antidiabetic drug or insulin. Patients with PTDM were divided into subgroups according to time of onset (early; <90 d vs. late, ≥90 d) and duration of diabetes (transient, <90 d vs. sustained ≥90 d). Results: The frequency of PTDM was 18.3%. In multivariate analysis age (p < 0.001), hepatitis C virus (HCV) infection (p < 0.05) and tacrolimus use (p < 0.001) were independent risk factors. Among 220 HCV+ patients, liver biopsy was performed in 158, the histological grade (3.3 ± 2.8 vs. 4.4 ± 3.1) and stage (0.9 ± 1.1 vs. 1.4 ± 1.2) were significantly more severe in patients with PTDM than in non‐diabetics. Incidence of PTDM in patients with severe fibrosis was 46.7%; 19.2% in nil or mild fibrosis (p < 0.05). Patient and graft survival were significantly worse, and cardiovascular events and life‐threatening infection episodes were more frequent in PTDM. Half of the patients had early PTDM, while 30.3% of patients with PTDM showed transient nature. Five‐ and 10‐yr death censored graft survival rates were worse in transient subgroup compared with sustained patients with diabetes (log rank 0.025) whereas there was no difference in outcome between early and late subgroups. Conclusions: Age, tacrolimus, and HCV are independent risk factors for PTDM. PTDM has a negative impact on both patient and graft survival, irrespective of the time of onset and duration of diabetes.     

Visceral fat is strongly associated with post‐transplant diabetes mellitus and glucose metabolism 1 year after kidney transplantation

Body composition after kidney transplantation is linked to glucose metabolism, and impaired glucose metabolism is associated with increased risk of cardiovascular events and death. One year after transplantation, we examined 150 patients for post‐transplant diabetes performing oral glucose tolerance tests and body composition measurements including visceral adipose tissue (VAT) content from dual‐energy X‐ray absorptiometry scans. We found that glucose metabolism was generally improved over the first year post‐transplant, and that the levels of VAT and percentage VAT of total body fat mass (VAT_%totBFM) were lowest in those with normal glucose tolerance and highest in those with post‐transplant diabetes mellitus. In a multivariable linear regression analysis, 87.4% of the variability in fasting glucose concentration was explained by insulin resistance (P<.001, HOMA‐IR index), beta cell function (P<.001, HOMA‐beta), VAT_%totBFM (P=.007), and body mass index (BMI; P=.015; total model P<.001), while insulin resistance (P<.001) and beta cell function (P<.001) explained 31.9% of the variability in 2‐hour glucose concentration in a multivariable model (total model P<.001). VAT was associated with glucose metabolism to a larger degree than BMI. In conclusion, VAT is associated with hyperglycemia one year after kidney transplantation, and insulin resistance and beta cell function estimates are the most robust markers of glucose metabolism.     

Effect of new‐onset diabetes mellitus on arterial stiffness in renal transplantation

New onset diabetes (NODM) is a common and serious complication of kidney transplantation, and is associated with increased cardiovascular morbidity and mortality. Cardiovascular morbidity and mortality, in turn, are closely associated with arterial stiffening. We hypothesize that NODM may be associated with an increase in arterial stiffness in renal transplantation. We compared pulse wave velocity (PWV) and augmentation index in 318 renal transplant patients with (n = 57) and without NODM (n = 261). PWV was determined from pressure tracing over carotid and femoral arteries. Augmentation‐index was derived by pulse‐wave‐analysis using radial applanation tonometry. PWV was significantly higher in transplant recipients with NODM (10.5 m/s) compared with transplant patients without NODM (8.7 m/s, P = 0.0002). There was no difference in augmentation index between patients with (27.7%) and without NODM (28.1%, P = 0.87). When analyzed by multiple regression analysis, PWV was only significantly correlated to age (P < 0.0001), NODM (P = 0.0325), and systolic blood pressure (P = 0.0081). NODM in renal transplant patients may accelerate arterial stiffening, thereby contributing to cardiovascular morbidity and mortality.     

New onset diabetes mellitus post-kidney transplantation

The study explores the prevalence of unrecognized diabetes mellitus (DM), the incidence and risk factors new onset diabetes mellitus (NODM) and determines whether patient survival differs between patients with transient (NODM that resolves) compared with those with fixed NODM. This is a single center review of solitary kidney recipients transplanted from 1993 to 2003. Of the 381 patients without DM pre-transplant, 111 met criteria for DM post. Of these 17 were unrecognized to have DM, 31 had transient (resolved) NODM and 64 had fixed NODM. In a multivariate analysis, age, body mass index, repeat transplant and rejection were risk factors for NODM. In a separate analysis of only fixed NODM, tacrolimus use showed a trend for an independent association (HR 1.7 95% CI 0.95-2.9). NODM patient survival was comparable to non-diabetic recipients even up to 10 yr; however, excess mortality started to be seen in the fixed NODM subgroup at late follow up. Use of more stringent DM criteria results in a population with relatively good intermediate term survival and allows detection and treatment of early disease. Transient NODM represents approximately one third of NODM and has a relatively good prognosis.     

Incidence,risk factors,and outcomes of stroke post‐transplantation in patients receiving a steroid sparing immunosuppression protocol

Corticosteroid use after transplantation is associated with an increased incidence of cardiovascular events and death. Cerebrovascular disease is a common cause of morbidity and mortality post‐renal transplantation; however, a dedicated analysis of cerebrovascular disease in recipients of a steroid sparing protocol has not been reported. The aim of this study was to examine the incidence, risk factors, and outcomes of CVA in transplant recipients receiving a steroid sparing protocol. We retrospectively analyzed 1237 patients who received a kidney alone or a simultaneous pancreas and kidney (SPK) transplant. Fifty‐six of 1237 (4.53%) patients had a CVA post‐transplant. All‐cause mortality was significantly higher in the CVA group compared with the non‐CVA group, OR: 3.4 (1.7–7.0), p < 0.001. Factors found to be associated with increased risk of CVA by multivariate analysis were older age, HR: 1.07 (1.04–1.09), p < 0.001; diabetes at the time of transplantation, HR: 2.83 (1.42–5.64), p = 0.003; corticosteroid use pre‐transplant, HR: 3.27 (1.29–8.27), p = 0.013 and recipients of a SPK, HR: 4.03 (1.85–8.79), p < 0.001. This study has identified subgroups of patients who are at increased risk of CVA post‐transplant in patients otherwise receiving a steroid sparing immunosuppression protocol.     

肝移植术后糖尿病的最新进展

糖尿病是肝移植术后最常见的并发症之一,肝移植术后并发糖尿病的受者生存率及移植物长期存活率明显低于无糖尿病的肝移植受者。近年来,随着肝移植在中国迅速发展,肝移植术后糖尿病也引发了高度关注。尽管过去20余年对于移植后糖尿病(PTDM)的研究从未停歇,但仍有许多问题有待进一步研究解决。本文旨在总结肝移植术后糖尿病的最新研究进展,包括PTDM的定义与诊断标准,肝移植术后糖尿病的危险因素、预防及治疗等,以期加深对于肝移植术后糖尿病的认识和理解,并进行有效预防和治疗,从而提高肝移植受者长期存活率及生活质量。     

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...     

Long‐term patient survival and kidney allograft survival in post‐transplant diabetes mellitus: a single‐center retrospective study

A decade ago, observations suggested that post‐transplant diabetes mellitus (PTDM) was linked to allograft loss and shorter patient survival. Increasing awareness, improvements in care, and changes in the immunosuppressive regimen may have modified this association. Single‐center analysis of 1990 (age>18; transplantation date 1996–2012) primary kidney recipients (KTR). Patients with <12 months follow‐up were excluded. Diabetes was diagnosed according to ADA criteria and characterized as follows: No diabetes, PTDM in the first post‐transplant year not treated with glucose‐lowering medications (GLM) at 12 months, PTDM in the first post‐transplant year treated with GLM at 12 months, and pretransplant diabetes. Cox proportional hazards models were used to examine the relationship of PTDM with allograft and patient survival. Mean follow‐up time was 6.8 years for allograft survival and 7.4 years for patient survival. PTDM treated with medication at year one was not associated with allograft survival (HR 1.28, 95% CI 0.97–1.69), but was significantly associated with overall mortality and death with functioning graft (DWFG) (HR overall: 1.81, 95% CI 1.36–2.39; HR DWFG: 1.59 95% CI 1.05–2.38). In this cohort, KTR with PTDM being treated with glucose‐lowering medication at 12 months experienced significantly shorter overall survival and survival with functioning graft.     

Estimated impact of introduction of new diagnostic criteria for gestational diabetes mellitus

BACKGROUNDImplementation of new diagnostic criteria for gestational diabetes mellitus (GDM) are still a subject of debate, mostly due to concerns regarding the effects on the number of women diagnosed with GDM and the risk profile of the women newly diagnosed.AIMTo estimate the impact of the World Health Organization (WHO) 2013 criteria compared with the WHO 1999 criteria on the incidence of gestational diabetes mellitus as well as to determine the diagnostic accuracy for detecting adverse pregnancy outcomes. METHODSWe retrospectively analyzed a single center Dutch cohort of 3338 women undergoing a 75 g oral glucose tolerance test where the WHO 1999 criteria to diagnose GDM were clinically applied. Women were categorized into four groups: non-GDM by both criteria, GDM by WHO 1999 only (excluded from GDM), GDM by WHO 2013 only (newly diagnosed) and GDM by both criteria. We compared maternal characteristics, pregnancy outcomes and likelihood ratios for adverse pregnancy outcomes. RESULTSRetrospectively applying the WHO 2013 criteria increased the cohort incidence by 13.1%, from 19.3% to 32.4%. Discordant diagnoses occurred in 21.3%; 4.1% would no longer be labelled as GDM, and 17.2% were newly diagnosed. Compared to the non-GDM group, women newly diagnosed were older, had higher rates of obesity, higher diastolic blood pressure and higher rates of caesarean deliveries. Their infants were more often delivered preterm, large-for-gestational-age and were at higher risk of a 5 min Apgar score < 7. Women excluded from GDM were older and had similar pregnancy outcomes compared to the non-GDM group, except for higher rates of shoulder dystocia (4.3% vs 1.3%, P = 0.015). Positive likelihood ratios for adverse outcomes in all groups were generally low, ranging from 0.54 to 2.95.CONCLUSIONApplying the WHO 2013 criteria would result in a substantial increase in GDM diagnoses. Newly diagnosed women are at increased risk for pregnancy adverse outcomes. This risk, however, seems to be lower than those identified by the WHO 1999 criteria. This could potentially influence the treatment effect that can be achieved in this group. Evidence on treatment effects in newly diagnosed women is urgently needed.     

Increased morbidity and mortality in patients with diabetes mellitus after kidney transplantation as compared with non-diabetic patients.

The results of renal transplantation in patients with juvenile-onset diabetes mellitus were compared to those of a well-matched control group of non-diabetic patients. All transplantations were performed between 1977 and 1988. In the diabetic group hypertension (72 versus 41%), coronary artery disease (17 versus 0%), and peripheral vascular disease (19 versus 0%) had been significantly more frequent pretransplantation. Fewer diabetic patients had previously been treated with dialysis therapy (69 versus 97%). Graft function measured by creatinine clearance after 1 year follow-up, and incidence of proteinuria were not significantly different. The overall graft survival was significantly worse in the diabetic group compared to the control group: 42 versus 69% after 60 months and 21 versus 62% after 90 months. This was caused by a significantly worse patient survival in the diabetic group after 105 months: 28 versus 78% in the control group. The graft survival following exclusion of the patients who died with a functioning graft did not differ significantly between the groups after 60 and 90 months: 62 and 31% in the diabetic group and 69 and 62% in the control group. The existence of any vascular disease before transplantation, especially pre-existing peripheral vascular disease, had a significant effect on mortality in diabetic patients (P = 0.0003). After transplantation, diabetic patients had significantly more cerebrovascular accidents (23 versus 3%), peripheral vascular disease (31 versus 3%), and number of infections (1.9 versus 1.2). Retransplantation was carried out in each group to the same extent, with the same success rate.     

Elevated glycosylated haemoglobin (HbA1c) is a risk marker in coronary artery bypass surgery

Objective. To evaluate if glycosylated haemoglobin 1 (HbA_1c) was associated with increased risk of infection and mortality after coronary artery bypass grafting (CABG). Design. Prospective observational study. Preoperative HbA_1c concentrations were correlated to outcome in patients followed for an average of 3.5 years after CABG. Results. HbA_1c was ≥6% in 68% of 161 patients with diabetes mellitus (DM) and in 3% of 444 patients without DM. Superficial sternal wound infection was observed in 13.9% if HbA_1c ≥6% versus in 5.5% if <6% (p=0.007). Mediastinitis occurred in 4.9% if HbA_1c≥6% and in 2.1% if HbA_1c<6% (p=0.20) (Hazard ratio (HR) 1.9, 95% CI 0.6-5.9). Follow-up mortality was 18.9% in patients with HbA_1c≥6% compared to 4.1% if HbA_1c<6% (p<0.001) with HR 5.4, (95% CI 3.0-10.0) after multivariable adjustment. The risk of death was similar regardless of DM diagnosis. Conclusions. HbA_1c ≥6% was associated with an increased risk of postoperative superficial sternal wound infections and a trend for higher mediastinitis rate and significantly higher mortality three years after CABG.     

肾移植受者发生移植后糖尿病的危险因素分析及预测模型的构建

目的  分析肾移植受者发生移植后糖尿病（PTDM）的危险因素,建立PTDM预测模型并评价其预测价值。方法  回顾性分析915例肾移植受者的临床资料。根据有否发生PTDM,分为PTDM组（78例）和非PTDM组（837例）。收集受者的主要指标,对肾移植受者发生PTDM的危险因素进行单因素和多因素分析; 建立PTDM预测模型并评价其预测价值。结果  糖尿病家族史、体质量指数（BMI）、术前餐后2 h血糖、术前糖化血红蛋白是肾移植受者发生PTDM的独立危险因素。PTDM预测模型为logit（P）=2.199×糖尿病家族史（有=1,无=0）+0.109×BMI+0.151×餐后2 h血糖（mmol/L）+0.508×糖化血红蛋白（%）-9.123。受试者工作特征（ROC）曲线结果显示,联合4种预测因子预测肾移植受者发生PTDM的曲线下面积（AUC）为0.830[95%可信区间（CI）0.786~0.873],界值为0.0608,灵敏度为0.821,特异度为0.700,约登指数为0.521（P < 0.05）。结论  糖尿病家族史、BMI、术前餐后2 h血糖、术前糖化血红蛋白是肾移植受者发生PTDM的独立危险因素。联合4种预测因子的PTDM预测模型具有较好的预测价值。     

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.     

Rosiglitazone is a safe and effective treatment option of new-onset diabetes mellitus after renal transplantation

The purpose of this study was to assess the safety and efficacy of the insulin sensitizer rosiglitazone in patients with new-onset diabetes mellitus (NODM) after renal transplantation. Twenty-two patients with NODM after renal transplantation were selected to receive rosiglitazone therapy. All patients received prednisone, 15 patients were treated with tacrolimus and seven patients received cyclosporine A. For 16 of the 22 patients treatment with rosiglitazone therapy was successful and mean fasting blood glucose decreased from 182 +/- 17 to 127 +/- 7 mg/dl. Six patients were not treated successfully with rosiglitazone alone, one patient needed a second oral antidiabetic agent and four patients insulin therapy. In one patient rosiglitazone was stopped because of edema after 5 days. There were no changes either in serum creatinine concentrations, or cyclosporine and tacrolimus blood levels respectively. Treatment with rosiglitazone appears to be safe and effective in patients with NODM after renal transplantation.