RNA oxidation product, 8-oxo-7,8-dihydroguanosine (8-oxoGuo), has been associated with mortality in two cohorts of patients with type 2 diabetes (T2D). However, the potential effect of registered treatments decreasing urine 8-oxoGuo level remains unraveled. In the Steno-2 study intensified multifactorial intervention compared with conventional multifactorial therapy cut by half mortality in T2D patients with microalbuminuria. We assessed association between total mortality and 8-oxoGuo from advanced baseline and for 19.9 years, and from end of 7.8 years of intervention for 12.1 years.

In 1993, 160 T2D patients with microalbuminuria were included in the trial. Urine samples were available from 155 patients in 1995 (advanced baseline) and from 125 patients in 2001 (end of intervention). Cox regression was used for log2-transformed 8-oxoGuo and dichotomized (cut-off at median; low vs. high RNA oxidation).

During a follow-up of 19.9 years after advanced baseline, 89 died. From the end of 7.8 years of intervention and during remaining 12.1 years of observation, 61 of 125 died. From advanced baseline and onwards, no association between 8-oxoGuo and mortality was found (p=0.40). From end of intervention and onwards, a doubling of 8-oxoGuo showed a hazard ratio (HR) of 3.(95% CI [1.86−5.12]; p<0.001; z-score=4.36) after multiple adjustments. Patients with low 8-oxoGuo in the intensive-therapy group had the lowest risk of dying compared with high 8-oxoGuo in the conventional group from advanced baseline and onwards, HR 0.40 (95% CI [0.21−0.75]; p=0.004), and from end of intervention and onwards, HR 0.28 (95% CI [0.13−0.60]; p=0.001) adjusted for age and sex.

In T2D patients with microalbuminuria, urine 8-oxoGuo level after 7.8 years of multifactorial intervention was associated with total mortality during 12.1 years of post-trial follow-up. Patients with low 8-oxoGuo in the intensified multifactorial group had the lowest risk of dying.

Disclosure

L.K. Kjaer: None. J. Oellgaard: None. T. Henriksen: None. P. Gæde: None. O. Pedersen: None. H.E. Poulsen: None.

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