Longitudinal Associations of Body Mass Index, Waist Circumference, and Waist-to-Hip Ratio with Biomarkers of Oxidative Stress in Older Adults: Results of a Large Cohort Study

Background: In the literature, obesity is discussed as a determinant of high oxidative stress (OS). Hence, prevention or reduction of obesity could prevent high OS and subsequently serve as a target for “healthy aging.” Methods: Diacron’s reactive oxygen metabolites test (D-ROM) and total thiol levels (TTL), a marker of antioxidant defense capacity, were measured in 1,734 participants of a population-based cohort study of older adults (age range: 57–83 years) at 2 time points 3 years apart. The longitudinal associations of body mass index, waist-to-hip ratio, and waist circumference with D-ROM and TTL were assessed with multivariable adjusted generalized linear models. Dose-response analyses were conducted with restricted cubic splines. Results: D-ROM was not significantly associated with any of the weight measures. On the contrary, TTL showed statistically significant, inverse linear associations with all weight measures. Conclusion: A healthy body weight seems to be highly relevant for the antioxidative defense capacity of human beings. In contrast, D-ROM levels were independent of the study participant’s weight. Clinical trials are needed to corroborate if loss of weight by obese individuals can effectively increase TTL and subsequently also life expectancy

Factors associated with high oxidative stress in patients with type 2 diabetes: a meta-analysis of two cohort studies

ObjectiveOur objective is to identify the potential factors associated with serum Diacron’s reactive oxygen metabolites test (D-ROM) levels of patients with type 2 diabetes mellitus (T2DM) by conducting cross-sectional and longitudinal analyses in two large cohorts and further strengthening these results by performing a meta-analysis.MethodsSerum D-ROM concentrations were measured in 1045 and 1101 patients with T2DM from two independent cohort studies from Germany at baseline and repeatedly 3–4 years later. The cross-sectional and longitudinal associations of various potential determinants with D-ROM levels were assessed with a backwards selection algorithm in multivariable adjusted models.ResultsIn the meta-analysis of the cross-sectional analysis, female sex, low education, obesity, smoking, high total cholesterol, hemoglobin A1c ≥7%, no diabetes medication, a history of myocardial infarction, heart failure, a history of cancer and C reactive protein levels (CRP) >3 mg/L were statistically significantly associated with increased D-ROM levels in patients with T2DM. The meta-analysis of the longitudinal analysis revealed that old age, female sex, obesity, smoking, physical inactivity, high alcohol consumption, ≥5 years since diabetes diagnosis and CRP levels between 3 mg/L and 10 mg/L were statistically significantly associated with D-ROM levels measured 3–4 years later.Conclusions (validity, limitations and clinical applicability)This comprehensive analysis confirmed that several modifiable risk factors are being associated with oxidative stress in patients with T2DM within an observational study design. We discuss potential prevention measures against these risk factors that might help to reduce oxidative stress and to prevent some cases of premature mortality in patients with T2DM

Factors associated with high oxidative stress in patients with type 2 diabetes: a meta-analysis of two cohort studies.

In the meta-analysis of the cross-sectional analysis, female sex, low education, obesity, smoking, high total cholesterol, hemoglobin A1c ≥7%, no diabetes medication, a history of myocardial infarction, heart failure, a history of cancer and C reactive protein levels (CRP) >3 mg/L were statistically significantly associated with increased D-ROM levels in patients with T2DM. The meta-analysis of the longitudinal analysis revealed that old age, female sex, obesity, smoking, physical inactivity, high alcohol consumption, ≥5 years since diabetes diagnosis and CRP levels between 3 mg/L and 10 mg/L were statistically significantly associated with D-ROM levels measured 3-4 years later

Pre-diagnostic derivatives of reactive oxygen metabolites and the occurrence of lung, colorectal, breast and prostate cancer: An individual participant data meta-analysis of two large population-based studies.

Oxidative stress may be involved in carcinogenesis and biomarkers of oxidative stress like derivatives of reactive oxygen metabolites (d-ROM) may be useful for cancer prediction. However, no previous study assessed the association of pre-diagnostic d-ROM measurements with cancer incidence. We measured serum d-ROM levels in a cohort sample of n = 4,345 participants of the German ESTHER study and in a case-cohort sample of the Norwegian Tromsø study (cancer cases: n = 941; subcohort: n = 1,000). Moreover, d-ROM was repeatedly measured at follow-ups of both studies. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were derived by (weighted) multivariable-adjusted Cox regression with time-dependent modeling of d-ROM levels for incident lung, colorectal, breast and prostate cancer. Individual study results were pooled by random effects meta-analysis. The HRs (95% CI) for comparison of top and bottom d-ROM tertile were statistically significant for lung (1.90 [1.25-2.89]), colorectal (1.70 [1.15-2.51]) and breast cancer incidence (1.45 [1.01-2.09]) but not for prostate cancer incidence (1.20 [0.84-1.72]). In conclusion, this individual participant data meta-analysis of two large population-based cohort studies with repeated d-ROM measurements yielded evidence for an involvement of high oxidative stress in carcinogenesis. Given the observed associations of pre-diagnostic d-ROM measurements with lung, colorectal and breast cancer incidence, subjects with increased serum d-ROM levels should be recommended to reduce these levels by lifestyle changes including smoking cessation, a healthy diet and an increase in physical activity

Pre-diagnostic derivatives of reactive oxygen metabolites and the occurrence of lung, colorectal, breast and prostate cancer: An individual participant data meta-analysis of two large population-based studies.

Oxidative stress may be involved in carcinogenesis and biomarkers of oxidative stress like derivatives of reactive oxygen metabolites (d-ROM) may be useful for cancer prediction. However, no previous study assessed the association of pre-diagnostic d-ROM measurements with cancer incidence. We measured serum d-ROM levels in a cohort sample of n = 4,345 participants of the German ESTHER study and in a case-cohort sample of the Norwegian Tromsø study (cancer cases: n = 941; subcohort: n = 1,000). Moreover, d-ROM was repeatedly measured at follow-ups of both studies. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were derived by (weighted) multivariable-adjusted Cox regression with time-dependent modeling of d-ROM levels for incident lung, colorectal, breast and prostate cancer. Individual study results were pooled by random effects meta-analysis. The HRs (95% CI) for comparison of top and bottom d-ROM tertile were statistically significant for lung (1.90 [1.25-2.89]), colorectal (1.70 [1.15-2.51]) and breast cancer incidence (1.45 [1.01-2.09]) but not for prostate cancer incidence (1.20 [0.84-1.72]). In conclusion, this individual participant data meta-analysis of two large population-based cohort studies with repeated d-ROM measurements yielded evidence for an involvement of high oxidative stress in carcinogenesis. Given the observed associations of pre-diagnostic d-ROM measurements with lung, colorectal and breast cancer incidence, subjects with increased serum d-ROM levels should be recommended to reduce these levels by lifestyle changes including smoking cessation, a healthy diet and an increase in physical activity