Association of Type 2 Diabetes With Cyclooxygenase-Mediated Inflammation and Oxidative Stress in an Elderly Population

Abstract

Background— Involvement of cyclooxygenase (COX)-mediated inflammation in type 2 diabetes has not been studied, and the association between cytokine-mediated inflammation and diabetes is not fully clarified. Methods and Results— 15-Keto-dihydro-prostaglandin F 2α (a metabolite of prostaglandin F 2α and an indicator of COX-mediated inflammation), high-sensitivity C-reactive protein (CRP), serum amyloid protein A (SAA), 8-iso-PGF 2α (a nonenzymatic, free radical product of arachidonic acid and an indicator of oxidative stress), and α-tocopherol were measured in a population-based sample of 77-year-old men (n=765), in which 112 men had type 2 diabetes. The inflammatory indicators were increased in men with diabetes (urinary 15-keto-dihydro-PGF 2α , P <0.001, CRP and SAA, P <0.05). However, when adjusted for body mass index, waist circumference, or fasting insulin, no association was found between diabetes and CRP or SAA. The oxidative stress indicator 8-iso-PGF 2α in urine was increased ( P <0.01) in men with diabetes. Patients who were newly diagnosed with diabetes (<7 years since diagnosis) had increased urinary 15-keto-dihydro-PGF 2α and decreased α-tocopherol, but 8-iso-PGF 2α was unaltered. Conclusions— This is the first study to show that type 2 diabetes in elderly men is related to COX-mediated inflammation, reflected by enhanced prostaglandin formation. The high levels of cytokine-mediated acute-phase proteins observed in men with diabetes appear to be related to obesity and increased fasting insulin. The results further suggest that the appearance of chronic inflammation is an early process in the pathogenesis of diabetes, whereas oxidative injury may be a later process, possibly related to inflammation.