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Indicator of RNA oxidation in urine for the Prediction of Mortality in Patients with Type 2 Diabetes and Microalbuminuria: A Post-Hoc Analysis of the Steno-2 Trial

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OBJECTIVE: The RNA oxidation product, 8-oxo-7,8-dihydroguanosine (8-oxoGuo), has been associated with mortality in patients with type 2 diabetes (T2D). However, the identification and the potential effect of approved treatments decreasing urine 8-oxoGuo level remain unraveled. In the Steno-2 study intensified multifactorial treatment compared with conventional multifactorial treatment reduced mortality in T2D patients with microalbuminuria by 45 percent. We assessed association between 8-oxoGuo at advanced baseline and total mortality with up to 19.9 years follow-up and from end of intervention to end of follow-up up to (13.9 years).

MATERIALS AND METHODS: In 1993, 160 T2D patients with microalbuminuria were included in the Steno-2 trial. Urine samples from baseline were not available, but samples were available from 155 patients (97%) in 1995 (advanced baseline) and from 125 patients (96%) in 2001 (end of intervention). Hazard ratios (HR) for log2-transformed 8-oxoGuo and dichotomized (cut-off at median; low vs. high RNA oxidation) were estimated using Cox regressions.

RESULTS: During follow-up of 19.9 years after advanced baseline, 89 died and no association between 8-oxoGuo and mortality was found (p=0.40). From the end of 7.8 years of intervention and during remaining 13.9 years of observation, 61 died and doubling the urine 8-oxoGuo level was associated with mortality with a HR 3.08 (95% CI [1.86-5.12]; p<0.001) after multiple adjustments. Patients with low 8-oxoGuo in the intensified-treatment had the lowest risk of dying compared with high 8-oxoGuo in the conventional-treatment both from advanced baseline onwards, adjusted HR 0.40 (95% CI [0.21-0.75]; p=0.004), and from end of intervention onwards, adjusted HR 0.28 (95% CI [0.13-0.61]; p=0.001).

CONCLUSIONS: In T2D patients with microalbuminuria, high levels of urine 8-oxoGuo after 7.8 years of multifactorial intervention was associated with higher mortality during 13.9 years of post-trial follow-up. Patients with low 8-oxoGuo in the intensified treatment group had the lowest risk of dying.

OriginalsprogEngelsk
TidsskriftFree Radical Biology & Medicine
Vol/bind129
Sider (fra-til)247-255
Antal sider9
ISSN0891-5849
DOI
StatusUdgivet - dec. 2018

ID: 55275856