Association between lipid peroxidation and risk of type 2 diabetes in women

Abstract

In-vitro and animal studies demonstrate that lipid peroxidation plays an important role in the pathogenesis of type 2 diabetes (T2D). However, human data from prospective studies are limited and contradictory. We used data originally collected in two nested case-control studies of cancer to prospectively evaluate whether systemic levels of lipid peroxidation were associated with incidence of T2D in 1917 women who were 40–70 years old and diabetes-free at baseline. Lipid peroxidation was measured by urinary F₂-isoprostanes (F₂-IsoPs) and its major metabolite 2,3-dinor-5,6-dihydro-15-F_2t-IsoP (F₂-IsoP-M) with GC/NICI-MS assays. The Cox regression model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident T2D. After a median follow-up of 10.1 years, 187 women were diagnosed with T2D. Urinary concentrations of both F₂-IsoPs and F₂-IsoP-M were significantly higher in T2D cases than in non-cases. Both biomarkers were positively associated with subsequent risk of T2D in multivariable-adjusted Cox models. When further adjusted for body mass index (BMI), the positive association with F₂-IsoP-M was attenuated and no longer statistically significant, whereas the association with F₂-IsoPs remained (P for overall significance < 0.001). HR for T2D was 1.68 (95% CI: 1.13, 2.51) for the highest vs the lowest quartile of F₂-IsoPs. Moreover, this association appeared more pronounced among women with higher BMI. In summary, our study suggests that F₂-IsoPs could be of significance in T2D risk prediction among middle-aged and elderly women.

Keywords:

• Lipid peroxidation
• prospective study
• risk factor
• type 2 diabetes

Acknowledgments

The authors are grateful to the participants and research staff of the Shanghai Women’s Health Study for their contributions to the study. The authors thank Jie Wu, Regina Courtney and Rodica Cal-Chris for sample preparation. Sample preparation was conducted at the Survey and Biospecimen Shared Resources, which is supported in part by the Vanderbilt-Ingram Cancer Center (P30CA068485).

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Data described in the article, code book, and analytic codes will be made available upon request, pending approval by the data management and sharing committee of the Shanghai Women’s Health Study.

Additional information

Funding

This work was supported by the National Institutes of Health [grant numbers R01CA237895, R01CA122364, R01CA106591 and UM1CA182910]. GLM is in part supported by the Vanderbilt Diabetes Research and Training Center [P30DK020593]. The funders had no role in the design of the study; the collection, analysis, and interpretation of the data; the writing of the manuscript; and the decision to submit the manuscript for publication.