Oxidatively Damaged DNA/RNA and 8-Isoprostane Levels Are Associated With the Development of Type 2 Diabetes at Older Age: Results From a Large Cohort Study

Diabetes Care. 2020 Jan;43(1):130-136. doi: 10.2337/dc19-1379. Epub 2019 Oct 25.

Abstract

Objective: Oxidative stress is believed to play an important role in the pathophysiology of type 2 diabetes, but the few cohort studies that have assessed the association of oxidative stress biomarkers with type 2 diabetes incidence were small and reported inconclusive results.

Research design and methods: We examined the associations of urinary oxidized guanine/guanosine (OxGua) levels (a biomarker of DNA/RNA oxidation) and urinary 8-isoprostane levels (a biomarker of lipid peroxidation) with type 2 diabetes incidence in 7,828 individuals initially without diabetes from a population-based German cohort study with 14 years of follow-up. Hazard ratios (HRs) (95% CIs) per 1 SD were obtained using multivariable-adjusted Cox proportional hazards regression models.

Results: In the total population, weak but statistically significant associations with type 2 diabetes incidence were observed for OxGua levels (HR [95% CI] per 1 SD 1.05 [1.01; 1.09]) and 8-isoprostane levels (1.04 [1.00; 1.09]). Stratified analyses showed that associations of both biomarkers with type 2 diabetes incidence were absent in the youngest age-group (50-59 years) and strongest in the oldest age-group (65-75 years) of the cohort, with HR of OxGua levels 1.14 (1.05; 1.23) per 1 SD and of 8-isoprostane levels 1.22 (1.02; 1.45) per 1 SD.

Conclusions: These results from a large cohort study support suggestions that an imbalanced redox system contributes to the development of type 2 diabetes but suggest that this association becomes clinically apparent at older ages only, possibly as a result of reduced cellular repair capacity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Aged
  • Aging / physiology*
  • Biomarkers / metabolism
  • Biomarkers / urine
  • Cohort Studies
  • DNA / metabolism
  • DNA Damage / physiology*
  • Diabetes Mellitus, Type 2 / epidemiology*
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / urine
  • Dinoprost / analogs & derivatives*
  • Dinoprost / urine
  • Female
  • Follow-Up Studies
  • Germany / epidemiology
  • Humans
  • Incidence
  • Lipid Peroxidation / physiology
  • Male
  • Middle Aged
  • Oxidation-Reduction
  • Oxidative Stress / physiology*
  • RNA / metabolism

Substances

  • Biomarkers
  • 8-epi-prostaglandin F2alpha
  • RNA
  • DNA
  • Dinoprost