Published Online
on March 22, 2004

A more recent version of this article appeared on April 13, 2004

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Submitted on June 11, 2003
Revised on October 29, 2003
Accepted on January 21, 2004

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

Johanna Helmersson MD, Bengt Vessby MD, PhD, Anders Larsson MD, PhD, and Samar Basu PhD^*

From the Sections of Geriatrics and Clinical Nutrition Research (J.H., B.V., S.B.) and the Section of Clinical Chemistry (A.L.), Faculty of Medicine, Uppsala University, Uppsala, Sweden.

^* To whom correspondence should be addressed. E-mail: Samar.Basu{at}pubcare.uu.se.

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 F₂ (a metabolite of prostaglandin F₂ and an indicator of COX-mediated inflammation), high-sensitivity C-reactive protein (CRP), serum amyloid protein A (SAA), 8-iso-PGF₂ (a nonenzymatic, free radical product of arachidonic acid and an indicator of oxidative stress), and -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-PGF₂, 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-PGF₂ 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-PGF₂ and decreased -tocopherol, but 8-iso-PGF₂ 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.

Key words: diabetes mellitus • inflammation • prostaglandins • free radicals

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