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


METHODS
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.


METHODS
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.
Department of Internal Medicine 3, Technische Universität Dresden, University Hospital Carl Gustav Carus, Dresden, Germany.
Steffi
S
Kopprasch
Department of Medical Informatics and Biometry, Technische Universität Dresden, University Hospital Carl Gustav Carus, Dresden, Germany.
Dheban
D
Srirangan
Institute of Clinical Chemistry and Laboratory Medicine, Technische Universität Dresden, University Hospital Carl Gustav Carus, Dresden, Germany.
Sybille
S
Bergmann
Department of Internal Medicine 3, Technische Universität Dresden, University Hospital Carl Gustav Carus, Dresden, Germany.
Juergen
J
Graessler
Department of Internal Medicine 3, Technische Universität Dresden, University Hospital Carl Gustav Carus, Dresden, Germany.
Peter E H
PE
Schwarz
Department of Internal Medicine 3, Technische Universität Dresden, University Hospital Carl Gustav Carus, Dresden, Germany.
Stefan R
SR
Bornstein
D000704:Analysis of Variance; D001786:Blood Glucose / Q000378:metabolism; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000503:physiopathology* / Q000517:prevention & control; D005260:Female; D018149:Glucose Intolerance / Q000097:blood / Q000503:physiopathology*; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology*; D018570:Risk Assessment / Q000379:methods / Q000706:statistics & numerical data; D012307:Risk Factors
D001786:Blood Glucose; D007328:Insulin