Markers of oxidative stress and risk of type 2 diabetes mellitus: Results from the MONICA/KORA Augsburg Study 1984–2002

Background: We sought to elucidate the role of oxidative stress in the development of incident type 2 diabetes by measuring oxidized LDL (ox-LDL) and myeloperoxidase (MPO) in a large cohort study. Methods: Using a case-cohort design, serum levels of ox-LDL and MPO were measured in 460 cases with incident type 2 diabetes and 1,474 non-cases selected from a source population of 7,936 middle-aged men and women who participated in the population-based MONICA/KORA Augsburg studies between 1984–1995. The mean follow-up time was 10.9±4.7 years. Results: After adjustment for age, survey, and lifestyle factors, elevated ox-LDL was significantly associated with the risk of type 2 diabetes in both sexes. Hazard ratios (HR) and 95% confidence intervals (CI) were 2.39 (1.63–3.52) for men and 3.02 (1.81–5.03) for women, respectively, comparing tertile extremes. MPO, however, was significantly associated with type 2 diabetes development in women only (HR [95% CI] 1.77 [1.18–2.65]). Further adjustment for body mass index, systolic blood pressure, total cholesterol/HDL-cholesterol, family history of diabetes and markers of inflammation attenuated the observed HR and they became clearly non-significant for ox-LDL (p-trend=0.178 for men and 0.920 for women), but remained borderline significant for MPO in women (p-trend=0.063). Conclusions: Our findings indicate that markers of oxidative stress predict incident type 2 diabetes. However, the effect is not independent of other known risk factors for type 2 diabetes including lipids and markers of inflammation. Further studies should also consider potential sex differences.