肝移植术后患者葡萄糖耐量的调节：环孢素与他克莫司治疗的影响

Regulation of glucose tolerance in patients after liver transplantation: impact of cyclosporin versus tacrolimus therapy.

作者信息

Konrad T, Steinmüller T, Vicini P, Toffolo G, Grewerus D, Schüller A, Bechstein W O, Usadel K H, Cobelli C, Neuhaus P

机构信息

Department of Internal Medicine I, Center of Internal Medicine, J. W. Goethe-University, Frankfurt, Germany.

出版信息

Transplantation. 2000 May 27;69(10):2072-8. doi: 10.1097/00007890-200005270-00017.

DOI:10.1097/00007890-200005270-00017

PMID:10852599

Abstract

BACKGROUND

We investigated the factors regulating glucose homeostasis in 10 healthy (control) subjects, as well as in stable, long-term, liver-grafted patients receiving monotherapy in the form of either cyclosporin A (n=10) or tacrolimus (n=10).

METHODS

We measured insulin sensitivity, first- and second-phase insulin secretion, with a minimal modeling technique based on the analysis of glucose, insulin, and C-peptide profiles during frequently sampled intravenous glucose tolerance tests (FSIGTT). Proinsulin levels, as a marker of beta-cell dysfunction, were measured in the fasting state and during FSIGTT.

RESULTS

Glucose and insulin concentrations before and after glucose loading did not differ in liver transplant patients and in control subjects. Fasting C-peptide levels in both liver-grafted groups were higher than in healthy subjects and remained elevated during FSIGTT (P<0.05). Intravenous glucose tolerance [(K(G)), i.e. the slope of the regression of logarithm of the blood glucose concentrations vs. time], insulin sensitivity, and first-phase insulin secretion did not differ in liver-grafted groups and healthy subjects. Second-phase insulin secretion was about 56% higher in liver-grafted patients than in controls (P<0.05). Body mass index was the overall determinant of insulin sensitivity in all groups.

CONCLUSIONS

Long-term monotherapy with cyclosporin A or tacrolimus has no deleterious effects on insulin sensitivity, first-phase insulin secretion, and insulin synthesis in liver transplant patients. Normal insulin sensitivity (posthepatic insulin effect) and enhanced second-phase insulin secretion (prehepatic insulin) point to an accelerated hepatic insulin clearance rate in liver transplant patients. Increased hepatic insulin clearance is compensated by enhanced insulin secretion, indicating that insulin clearance is the major determinant of pancreatic function in liver-grafted patients.

摘要

背景

我们研究了10名健康（对照）受试者以及接受环孢素A（n = 10）或他克莫司（n = 10）单药治疗的稳定、长期肝移植患者体内调节葡萄糖稳态的因素。

方法

我们采用一种基于频繁采样静脉葡萄糖耐量试验（FSIGTT）期间葡萄糖、胰岛素和C肽曲线分析的最小建模技术，测量胰岛素敏感性、第一相和第二相胰岛素分泌。在空腹状态和FSIGTT期间测量胰岛素原水平，作为β细胞功能障碍的标志物。

结果

肝移植患者和对照受试者在葡萄糖负荷前后的葡萄糖和胰岛素浓度没有差异。两个肝移植组的空腹C肽水平均高于健康受试者，并且在FSIGTT期间一直保持升高（P<0.05）。肝移植组和健康受试者的静脉葡萄糖耐量[K(G)，即血糖浓度对数与时间的回归斜率]、胰岛素敏感性和第一相胰岛素分泌没有差异。肝移植患者的第二相胰岛素分泌比对照组高约56%（P<0.05）。体重指数是所有组中胰岛素敏感性的总体决定因素。

结论

环孢素A或他克莫司长期单药治疗对肝移植患者的胰岛素敏感性、第一相胰岛素分泌和胰岛素合成没有有害影响。正常的胰岛素敏感性（肝后胰岛素效应）和增强的第二相胰岛素分泌（肝前胰岛素）表明肝移植患者的肝脏胰岛素清除率加快。肝脏胰岛素清除增加通过增强胰岛素分泌得到补偿，这表明胰岛素清除是肝移植患者胰腺功能的主要决定因素。