Hjelmesaeth Jøran, Jenssen Trond, Hagen Monica, Egeland Thore, Hartmann Anders
Department of Medicine, Section of Nephrology, Rikshospitalet, University of Oslo, Oslo, Norway.
Metabolism. 2003 May;52(5):573-8. doi: 10.1053/meta.2003.50092.
The high prevalence of post-transplant glucose intolerance and insulin resistance (IR) is associated with older age, family history of diabetes, immunosuppressive drugs, and antihypertensive therapy. However, the potential determinants of post-transplant beta-cell dysfunction are largely unknown. The objective of the present study was to address this issue in detail. A total of 167 previously nondiabetic renal transplant recipients underwent a 75-g oral glucose tolerance test (OGTT)10 weeks after transplantation. Serum glucose and insulin were measured at 0, 1, and 2 hours. Three insulin release indices (Secr(AUC), Secr(1.phase), and Secr(2.phase)) were calculated to assess the insulin secretory response as the dependent variable. To account for variations in insulin sensitivity (IS), beta-cell function was also estimated as the disposition index (DI); the product of the IS index (ISI(TX)) and Secr(1.phase). Increasing age was strongly and independently associated with a blunted insulin secretory response even after adjustment for IS (P =.001). An 80-year-old recipient had an approximately 50% lower insulin release than a 20-year-old individual, based on the linear regression model. Cytomegalovirus (CMV) disease and treatment with furosemide were both independently associated with beta-cell dysfunction (DI; P <.001 and P =.008). Patients treated with angiotensin-converting enzyme (ACE)-inhibitors had an enhanced absolute insulin release, but the DI was similar in both treated and untreated recipients. We conclude that older age is an important determinant of beta-cell dysfunction after renal transplantation. CMV disease and treatment with furosemide may also negatively influence pancreatic insulin release in renal transplant recipients.
移植后葡萄糖不耐受和胰岛素抵抗（IR）的高发生率与高龄、糖尿病家族史、免疫抑制药物及抗高血压治疗有关。然而，移植后β细胞功能障碍的潜在决定因素在很大程度上尚不清楚。本研究的目的是详细探讨这一问题。共有167例既往无糖尿病的肾移植受者在移植后10周接受了75克口服葡萄糖耐量试验（OGTT）。在0、1和2小时测定血清葡萄糖和胰岛素水平。计算三个胰岛素释放指数（Secr（AUC）、Secr（1期）和Secr（2期））以评估作为因变量的胰岛素分泌反应。为了考虑胰岛素敏感性（IS）的差异，β细胞功能也被估计为处置指数（DI）；即IS指数（ISI（TX））与Secr（1期）的乘积。即使在调整IS后，年龄增长仍与胰岛素分泌反应减弱密切且独立相关（P = 0.001）。根据线性回归模型，80岁的受者胰岛素释放比20岁的个体低约50%。巨细胞病毒（CMV）疾病和使用速尿治疗均与β细胞功能障碍（DI；P < 0.001和P = 0.008）独立相关。接受血管紧张素转换酶（ACE）抑制剂治疗的患者绝对胰岛素释放增加，但治疗组和未治疗组受者的DI相似。我们得出结论，高龄是肾移植后β细胞功能障碍的重要决定因素。CMV疾病和使用速尿治疗也可能对肾移植受者的胰腺胰岛素释放产生负面影响。
