Handisurya Ammon, Kerscher Corinna, Tura Andrea, Herkner Harald, Payer Berit Anna, Mandorfer Mattias, Werzowa Johannes, Winnicki Wolfgang, Reiberger Thomas, Kautzky-Willer Alexandra, Pacini Giovanni, Säemann Marcus, Schmidt Alice
Department of Internal Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria.
Institute of Neurosciences, CNR, Padova, Italy.
PLoS One. 2016 Jan 6;11(1):e0145319. doi: 10.1371/journal.pone.0145319. eCollection 2016.
Calcineurin-inhibitors and hepatitis C virus (HCV) infection increase the risk of post-transplant diabetes mellitus. Chronic HCV infection promotes insulin resistance rather than beta-cell dysfunction. The objective was to elucidate whether a conversion from tacrolimus to cyclosporine A affects fasting and/or dynamic insulin sensitivity, insulin secretion or all in HCV-positive renal transplant recipients.
In this prospective, single-center study 10 HCV-positive renal transplant recipients underwent 2h-75g-oral glucose tolerance tests before and three months after the conversion of immunosuppression from tacrolimus to cyclosporine A. Established oral glucose tolerance test-based parameters of fasting and dynamic insulin sensitivity and insulin secretion were calculated. Data are expressed as median (IQR).
After conversion, both fasting and challenged glucose levels decreased significantly. This was mainly attributable to a significant amelioration of post-prandial dynamic glucose sensitivity as measured by the oral glucose sensitivity-index OGIS [422.17 (370.82-441.92) vs. 468.80 (414.27-488.57) mL/min/m2, p = 0.005), which also resulted in significant improvements of the disposition index (p = 0.017) and adaptation index (p = 0.017) as markers of overall glucose tolerance and beta-cell function. Fasting insulin sensitivity (p = 0.721), insulinogenic index as marker of first-phase insulin secretion [0.064 (0.032-0.106) vs. 0.083 (0.054-0.144) nmol/mmol, p = 0.093) and hepatic insulin extraction (p = 0.646) remained unaltered. No changes of plasma HCV-RNA levels (p = 0.285) or liver stiffness (hepatic fibrosis and necroinflammation, p = 0.463) were observed after the conversion of immunosuppression.
HCV-positive renal transplant recipients show significantly improved glucose-stimulated insulin sensitivity and overall glucose tolerance after conversion from tacrolimus to cyclosporine A. Considering the HCV-induced insulin resistance, HCV-positive renal transplant recipients may benefit from a cyclosporine A-based immunosuppressive regimen.
ClinicalTrials.gov NCT02108301.
钙调神经磷酸酶抑制剂和丙型肝炎病毒（HCV）感染会增加移植后糖尿病的风险。慢性HCV感染会促进胰岛素抵抗而非β细胞功能障碍。目的是阐明从他克莫司转换为环孢素A是否会影响HCV阳性肾移植受者的空腹和/或动态胰岛素敏感性、胰岛素分泌或全部情况。
在这项前瞻性单中心研究中，10名HCV阳性肾移植受者在免疫抑制从他克莫司转换为环孢素A之前和之后三个月接受了2小时75克口服葡萄糖耐量试验。计算基于口服葡萄糖耐量试验建立的空腹和动态胰岛素敏感性及胰岛素分泌参数。数据以中位数（四分位间距）表示。
转换后，空腹血糖和激发后血糖水平均显著降低。这主要归因于口服葡萄糖敏感性指数OGIS测量的餐后动态葡萄糖敏感性显著改善[422.17（370.82 - 441.92）对468.80（414.27 - 488.57）mL/min/m2，p = 0.005]，这也导致作为总体葡萄糖耐量和β细胞功能标志物的处置指数（p = 0.017）和适应指数（p = 0.017）显著改善。空腹胰岛素敏感性（p = 0.721）、作为第一相胰岛素分泌标志物的胰岛素生成指数[0.064（0.032 - 0.106）对0.083（0.054 - 0.144）nmol/mmol，p = 0.093]和肝脏胰岛素提取率（p = 0.646）保持不变。免疫抑制转换后未观察到血浆HCV - RNA水平（p = 0.285）或肝脏硬度（肝纤维化和坏死性炎症，p = 0.463）的变化。
HCV阳性肾移植受者从他克莫司转换为环孢素A后，葡萄糖刺激的胰岛素敏感性和总体葡萄糖耐量显著改善。考虑到HCV诱导的胰岛素抵抗，HCV阳性肾移植受者可能受益于基于环孢素A的免疫抑制方案。
ClinicalTrials.gov NCT02108301。
