Oxidative stress and response in relation to coronary artery disease in type 1 diabetes.
OBJECTIVE
Although oxidative stress (OxS) is thought to contribute to atherosclerosis and coronary artery disease (CAD), little is known about the variability in an individual's ability to respond to OxS. Therefore, we assessed potential indices of response to OxS and evaluated whether they modify the association between OxS and CAD.


METHODS
We evaluated plasma α- and γ-tocopherol per unit cholesterol (potential response markers); urinary 15-isoprostane F2t per milligram creatinine (isoprostane [IsoP], a potential stress marker); and the α-tocopherol-to-IsoP ratio (as a measure of response to stress), measured three times during 20 years of follow-up, in relation to CAD incidence in a cohort with childhood-onset type 1 diabetes (n = 658; mean age at baseline, 28 years; duration of diabetes, 19 years). Participants with three samples (blood and either 24-h or overnight urine) available before the onset of CAD or the end of follow-up (n = 356) were selected for study.


RESULTS
In multivariable mixed models, α-tocopherol over time was inversely associated with CAD (β = -0.27; P = 0.02), whereas a direct association was observed for IsoP (β = 0.0008; P = 0.06). Moreover, the α-tocopherol-to-IsoP ratio was strongly and inversely related to CAD incidence (β = -0.72; P = 0.003), whereas in a separate model including α-tocopherol and IsoP, both biomarkers maintained statistical significance. No association was observed for γ-tocopherol (β = -0.22; P = 0.54).


CONCLUSIONS
These data suggest that a greater potential capability (α-tocopherol) to respond to OxS (urinary IsoP) relates to CAD incidence.
Corresponding author: Tina Costacou, costacout@edc.pitt.edu.
Tina
T
Costacou
Rhobert W
RW
Evans
Gerald L
GL
Schafer
Trevor J
TJ
Orchard
D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000652:urine; D003324:Coronary Artery Disease / Q000150:complications / Q000453:epidemiology / Q000503:physiopathology*; D003404:Creatinine / Q000652:urine; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000453:epidemiology / Q000503:physiopathology*; D015237:Dinoprost / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D015994:Incidence; D028421:Isoprostanes / Q000652:urine; D008297:Male; D018384:Oxidative Stress; D055815:Young Adult; D024502:alpha-Tocopherol / Q000097:blood
D015415:Biomarkers; D028421:Isoprostanes; C075750:8-epi-prostaglandin F2alpha; D003404:Creatinine; D015237:Dinoprost; D024502:alpha-Tocopherol