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- Title
Cross-Sectional Association of Oxidative Stress, Insulin Resistance, and Prediabetic Phenotypes: The Framingham Offspring Study.
- Authors
Meigs, James B.; Larson, Martin G.; Fox, Caroline S.; Keaney, John F.; Vasan, Ramachandran S.; Benjamin, Emelia J.
- Abstract
Systemic oxidative stress causes insulin resistance (IR) in rodents. We tested the hypothesis that oxidative stress and IR are associated in humans. We used cross-sectional data from 2002 non-diabetic (no anti-diabetes treatment, FPG <7.0 mmol/l) subjects of the community-based Framingham Offspring Study (mean age 54 yr, 55% women). We measured IR with the homeostasis model (HOMA-IR), defined categorical IR as HOMA-IR in the top 25th%ile and measured systemic oxidative stress with the ratio of urine 8-epi-PGF2a/creatinine. We used age-sex-adjusted linear and logistic regression models to test the hypothesis that systemic oxidative stress is positively associated with IR in people without type 2 diabetes and among the subgroup of those at moderate-to-elevated risk of diabetes. Across 8-epi-PGF2a/creatinine tertiles, the prevalence of IR increased (18.0%, 27.5%, and 29.4%; age-sex-adjusted model chi square p<0.0001), as did adjusted mean levels of HOMA-IR (3.28, 3.83, 4.06 units; p<0.0001). The IR-oxidative stress association was slightly 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 >=30 kg/m2), 39% had metabolic syndrome (ATP3 definition) and 37% had IFG (fasting glucose 5.6-6.9 mmol/l). Among 528 obese participants, adjusted IR prevalence was 41.3%, 60.6%, and 54.2% across 8-epi-PGF2a/creatinine tertile (age-sex-adjusted model chi square p=0.005). Among 781 with metabolic syndrome, IR prevalence was 41.3%, 56.7%, and 51.7% across 8-epi-PGF2a/creatinine tertile (p=0.0025). Among 749 with IFG, adjusted IR prevalence was 39.6%, 47.2%, and 51.6% across 8-epi-PGF2(/creatinine tertile (p=0.00). BMI-, metabolic syndrome-, and IFG-by-8-epi-PGF2a/creatinine interactions were significant (all p<0.00) for mean HOMA-IR level but not (p>0.05) for IR prevalence. We conclude that systemic oxidative stress is positively associated with a surrogate marker of IR in people without diabetes, even after accounting for BMI. Elevated oxidative stress in people at elevated risk of type 2 diabetes is associated with evidence of especially high levels of IR. ADA-Funded Research
- Publication
Diabetes, 2007, Vol 56, pA247
- ISSN
0012-1797
- Publication type
Academic Journal