全身氧化应激与胰岛素抵抗/敏感性指标之间的关联——PREDIAS研究

Association between systemic oxidative stress and insulin resistance/sensitivity indices - the PREDIAS study.

作者信息

Kopprasch Steffi, Srirangan Dheban, Bergmann Sybille, Graessler Juergen, Schwarz Peter E H, Bornstein Stefan R

机构信息

Department of Internal Medicine 3, Technische Universität Dresden, University Hospital Carl Gustav Carus, Dresden, Germany.

Department of Medical Informatics and Biometry, Technische Universität Dresden, University Hospital Carl Gustav Carus, Dresden, Germany.

出版信息

Clin Endocrinol (Oxf). 2016 Jan;84(1):48-54. doi: 10.1111/cen.12811. Epub 2015 Jun 4.

DOI:10.1111/cen.12811

PMID:25940301

Abstract

OBJECTIVE

Systemic oxidative stress has been causally related to insulin resistance and the subsequent development of type 2 diabetes mellitus (T2D). We investigated associations between circulating oxidative stress markers and different surrogate indexes of insulin sensitivity/resistance.

PATIENTS

Cross-sectional data were obtained from 1183 subjects with normal glucose tolerance (NGT), 280 subjects with impaired glucose tolerance (IGT) and 69 newly detected T2D individuals entering the PREDIAS (prevention of diabetes) study.

MEASUREMENTS

Following oral glucose tolerance test, five different insulin sensitivity/resistance indices were estimated: homoeostasis model of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), early phase insulin release (EPIR), insulin sensitivity index (ISI) and disposition index (DI). Additionally, circulating phagocyte generation of reactive oxygen species (ROS) and plasma total antioxidant capacity (TAC) was measured.

RESULTS

After adjustment for five covariates, HOMA-IR was significantly increased in IGT and T2D subjects when compared to NGT subjects (P = 0·000). QUICKI (P = 0·000), ISI (P = 0·000), EPIR (0·005/0·012) and DI (P = 0·000) were significantly attenuated in IGT and T2D. The prevalence of IGT and T2D individuals increased with increasing ROS generation and TAC tertiles. Increased systemic ROS generation was paralleled by increased HOMA-IR (P < 0·001, tertile 1/T1/vs tertile 3/T3/), decreased QUICKI (P < 0·001, T1 vs T3) and decreased ISI (P < 0·05, T1 vs T3). A similar tendency for indices was observed when comparing TAC tertiles: increase in HOMA-IR, decrease in QUICKI and ISI (P < 0·001, T1 vs T3 each). EPIR and DI did not differ significantly across ROS generation and TAC tertiles.

CONCLUSIONS

Systemic oxidative stress is associated with elevated insulin resistance index HOMA-IR, and decreased insulin sensitivity surrogates QUICKI and ISI.

摘要

目的

全身性氧化应激与胰岛素抵抗及随后2型糖尿病（T2D）的发生存在因果关系。我们研究了循环氧化应激标志物与胰岛素敏感性/抵抗的不同替代指标之间的关联。

患者

横断面数据来自1183例糖耐量正常（NGT）的受试者、280例糖耐量受损（IGT）的受试者以及69例新诊断的T2D个体，这些个体均参与了PREDIAS（糖尿病预防）研究。

测量

口服葡萄糖耐量试验后，评估了五个不同的胰岛素敏感性/抵抗指标：胰岛素抵抗稳态模型（HOMA-IR）、定量胰岛素敏感性检查指数（QUICKI）、早期胰岛素释放（EPIR）、胰岛素敏感性指数（ISI）和处置指数（DI）。此外，还测量了循环吞噬细胞活性氧（ROS）的生成和血浆总抗氧化能力（TAC）。

结果

在对五个协变量进行调整后，与NGT受试者相比，IGT和T2D受试者的HOMA-IR显著升高（P = 0·000）。IGT和T2D患者的QUICKI（P = 0·000）、ISI（P = 0·000）、EPIR（0·005/0·012）和DI（P = 0·000）显著降低。IGT和T2D个体的患病率随ROS生成和TAC三分位数的增加而升高。全身性ROS生成增加与HOMA-IR升高（P < 0·001，三分位数1/T1/与三分位数3/T3/相比）、QUICKI降低（P < 0·001，T1与T3相比）和ISI降低（P < 0·05，T1与T3相比）平行。比较TAC三分位数时，各指标也观察到类似趋势：HOMA-IR升高，QUICKI和ISI降低（各P < 0·001，T1与T3相比）。EPIR和DI在ROS生成和TAC三分位数之间无显著差异。