Strøm Halden Thea Anine, Åsberg Anders, Vik Karen, Hartmann Anders, Jenssen Trond
Department of Transplant Medicine, Section of Nephrology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
Nephrol Dial Transplant. 2014 Apr;29(4):926-33. doi: 10.1093/ndt/gft536. Epub 2014 Jan 22.
New-onset diabetes after transplantation (NODAT) is a common complication after renal transplantation. There are limited available oral drugs to treat hyperglycaemia in this population owing to reduced renal function, potential interactions with immunosuppressive drugs and adverse effects such as hypoglycaemic events that may increase the cardiovascular risk. This study was initiated to investigate efficacy and safety of sitagliptin treatment that may represent a novel alternative in renal transplant recipients.
Nineteen long-term stable renal transplant recipients with NODAT were included in a controlled, cross-over study and randomized to first receive either sitagliptin 50-100 mg/day or a sitagliptin-free period of 4 weeks. Median age (interquartile range, IQR) was 67 (62-72) years (12 males/7 females), all studied 1 (1-3) year after transplantation. The immunosuppressive regimen was a triple calcineurin inhibitor-based therapy. Oral glucose tolerance test (OGTT) with insulin and C-peptide responses and laser Doppler (LD) flowmetry assessment of endothelial function were performed at baseline and after each treatment period. Home measurements of plasma glucose were performed daily during the study.
The median (IQR) first- and second-phase insulin secretion responses increased significantly by 56.3% (45.2-112.6%, P = 0.005) and 39.3% (26.5-81.0%, P = 0.006), respectively, following sitagliptin treatment as compared with no sitagliptin treatment. Fasting and 2-h plasma glucose concentrations fell significantly {0.9 mmol/L [0.5-1.7 mmol/L (16.2 mg/dL), P = 0.003] and 2.9 mmol/L [0.5-6.4 mmol/L (52.3 mg/dL), P = 0.004], respectively}, as did also home measurements of plasma glucose. Endothelial function and plasma markers of cardiovascular risk were unaffected. No serious adverse events were observed. Two mild and asymptomatic hypoglycaemic episodes were observed in combination with glipizide.
Sitagliptin increases insulin secretion and reduces fasting and postprandial plasma glucose in renal transplant recipients with NODAT. The short-term treatment was well tolerated, and sitagliptin seems safe in this population.
移植后新发糖尿病（NODAT）是肾移植后常见的并发症。由于肾功能减退、与免疫抑制药物的潜在相互作用以及可能增加心血管风险的低血糖事件等不良反应，治疗该人群高血糖的口服药物有限。本研究旨在调查西他列汀治疗的疗效和安全性，其可能是肾移植受者的一种新选择。
19例患有NODAT的长期稳定肾移植受者纳入一项对照交叉研究，随机分为先接受西他列汀50 - 100mg/天治疗或为期4周的无西他列汀治疗期。中位年龄（四分位间距，IQR）为67（62 - 72）岁（12例男性/7例女性），均在移植后1（1 - 3）年接受研究。免疫抑制方案为基于三联钙调神经磷酸酶抑制剂的治疗。在基线及每个治疗期后进行口服葡萄糖耐量试验（OGTT）及胰岛素和C肽反应测定，以及激光多普勒（LD）血流仪评估内皮功能。研究期间每天进行家庭血糖测量。
与未接受西他列汀治疗相比，接受西他列汀治疗后，第一相和第二相胰岛素分泌反应的中位数（IQR）分别显著增加56.3%（45.2 - 112.6%，P = 0.005）和39.3%（26.5 - 81.0%，P = 0.006）。空腹和餐后2小时血糖浓度显著下降{分别为0.9mmol/L[0.5 - 1.7mmol/L（16.2mg/dL），P = 0.003]和2.9mmol/L[0.5 - 6.4mmol/L（52.3mg/dL），P = 0.004]}，家庭血糖测量结果也是如此。内皮功能和心血管风险的血浆标志物未受影响。未观察到严重不良事件。与格列吡嗪联合使用时观察到2例轻度无症状低血糖发作。
西他列汀可增加NODAT肾移植受者的胰岛素分泌，降低空腹和餐后血糖。短期治疗耐受性良好，西他列汀在该人群中似乎是安全的。
