DOI: 10.2337/dc07-0817
Association of Oxidative Stress, Insulin Resistance, and Diabetes Risk Phenotypes: The Framingham Offspring Study
1 General Medicine Division and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA jmeigs{at}partners.org ABSTRACT Objective:Systemic oxidative stress causes insulin resistance (IR) in rodents. We tested the hypothesis that oxidative stress and IR are associated in humans. Research Design and Methods:We used cross-sectional data from 2002 non-diabetic subjects of the community-based Framingham Offspring Study. We measured IR with the homeostasis model and defined categorical IR as HOMA-IR >75%ile. We measured oxidative stress using the ratio of urine 8-epi-PGF2a/creatinine, and used age-sex-adjusted regression models to test the association of oxidative stress with IR in people without diabetes and among subgroups at elevated risk of diabetes.
Results:Across 8-epi-PGF2a/creatinine tertile the prevalence of IR increased (18.0%, 27.5%, and 29.4%; p <0.0001), as did mean levels of HOMA-IR (3.28, 3.83, 4.06 units; p<0.0001). The IR-oxidative stress association was attenuated by additional adjustment for BMI (p=0.06 across tertile for IR prevalence, p=0.004 for mean HOMA-IR). Twenty-six percent of participants were obese (BMI Conclusions:Systemic oxidative stress is associated with IR in people at average or elevated risk of diabetes, even after accounting for BMI.
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