Hagen Monica, Hjelmesaeth Joran, Jenssen Trond, Morkrid Lars, Hartmann Anders
Department of Medicine, Section of Nephrology, Rikshospitalet, 0027 Oslo, Norway.
Nephrol Dial Transplant. 2003 Oct;18(10):2154-9. doi: 10.1093/ndt/gfg338.
It is well known that both insulin resistance and insulin deficiency are involved in the pathogenesis of post-transplant diabetes mellitus (PTDM), but the relative importance of the two different mechanisms is still under debate. The present prospective longitudinal study was performed over 6 years to investigate the impact of impaired insulin secretion (ISec) and insulin sensitivity (IS) in the development of PTDM in renal transplant recipients.
A total of 95 non-diabetic patients underwent a 75 g oral glucose tolerance test (OGTT) 10 weeks post-transplant. Six years later, 63 of these recipients were re-examined, the majority (n = 58) with an OGTT. Fasting, 1- and 2-h insulin and glucose levels were measured and used to estimate the insulin secretory response and IS both at baseline and at follow-up.
The proportion of recipients with normal glucose tolerance (NGT) rose from 46% (baseline) to 65% (follow-up) (P = 0.008), and median fasting and 2-h serum glucose were reduced by 0.7 mmol/l (P < 0.001) and 1.3 mmol/l (P = 0.039), respectively. The recipients with PTDM at follow-up had a significant decline in the estimated median first and second phase ISec (-58 and -47%, respectively, P = 0.005 for both). The patients who normalized their glucose tolerance from PTDM or IGT at baseline to NGT at follow-up increased their IS significantly (68%, P = 0.002) without significant alterations in ISec.
Impaired ISec seems to be the dominant mechanism in the development of PTDM after renal transplantation. In contrast, normalization of glucose intolerance is associated with improved IS.
众所周知，胰岛素抵抗和胰岛素缺乏均参与移植后糖尿病（PTDM）的发病机制，但这两种不同机制的相对重要性仍存在争议。本前瞻性纵向研究历时6年，旨在调查胰岛素分泌受损（ISec）和胰岛素敏感性（IS）对肾移植受者发生PTDM的影响。
95例非糖尿病患者在移植后10周接受了75克口服葡萄糖耐量试验（OGTT）。6年后，对其中63例受者进行了复查，大多数（n = 58）进行了OGTT。测量空腹、1小时和2小时的胰岛素和葡萄糖水平，并用于评估基线和随访时的胰岛素分泌反应和IS。
葡萄糖耐量正常（NGT）的受者比例从46%（基线）升至65%（随访）（P = 0.008），空腹和2小时血清葡萄糖中位数分别降低了0.7 mmol/l（P < 0.001）和1.3 mmol/l（P = 0.039）。随访时发生PTDM的受者估计的第一和第二阶段ISec中位数显著下降（分别为-58%和-47%，两者P = 0.005）。那些从基线时的PTDM或糖耐量受损（IGT）转变为随访时NGT的患者，其IS显著增加（68%，P = 0.002），而ISec无显著变化。
ISec受损似乎是肾移植后发生PTDM的主要机制。相反，糖耐量异常的正常化与IS改善有关。
