Insulin resistance in the elderly: The Rotterdam Study

Insulin resistance is a diminished ability to keep the serum glucose low with insulin levels in the normal range. Subjects with raised insulin resistance therefore usually have increased serum insulin levels. When the B-cells of the pancreas are no longer able to produce these increased amounts of insulin, serum glucose increases and diabetes mellitus develops. Raised insulin resistance and the ensuing hyperinsulinemia increase with age. Because hyperinsulinemia is a risk factor for several (chronic) diseases which are common in the elderly, insulin resistance was assessed as part of a large population-based study to chronic diseases in the elderly, the Rotterdam Study. In this first chapter a general description of the Rotterdam Study is given, with an overview of the measurements of the glucose metabolism. This is followed by a review on the oral glucose tolerance test. Finally, the results of a validation study are reported on the nonfasting oral glucose tolerance test, as used in the Rotterdam Study

Peroxiredoxin 4, a novel circulating biomarker for oxidative stress and the risk of incident cardiovascular disease and all-cause mortality

BACKGROUND: Oxidative stress has been suggested to play a key role in the development of cardiovascular disease (CVD). The aim of our study was to investigate the associations of serum peroxiredoxin 4 (Prx4), a hydrogen peroxide-degrading peroxidase, with incident CVD and all-cause mortality. We subsequently examined the incremental value of Prx4 for the risk prediction of CVD compared with the Framingham risk score (FRS). METHODS AND RESULTS: We performed Cox regression analyses in 8141 participants without history of CVD (aged 28 to 75 years; women 52.6%) from the Prevention of Renal and Vascular End-stage Disease (PREVEND) study in Groningen, The Netherlands. Serum Prx4 was measured by an immunoluminometric assay in baseline samples. Main outcomes were: (1) incident CVD events or CVD mortality and (2) all-cause mortality during a median follow-up of 10.5 years. In total, 708 participants (7.8%) developed CVD events or CVD mortality, and 517 participants (6.3%) died. Baseline serum Prx4 levels were significantly higher in participants with incident CVD events or CVD mortality and in those who died than in participants who remained free of outcomes (both P<0.001). In multivariable models with adjustment for Framingham risk factors, hazard ratios were 1.16 (95% CI 1.06 to 1.27, P<0.001) for incident CVD events or CVD mortality and 1.17 (95% CI 1.06 to 1.29, P=0.003) for all-cause mortality per doubling of Prx4 levels. After the addition of Prx4 to the FRS, the net reclassification improvement was 2.7% (P=0.01) using 10-year risk categories of CVD. CONCLUSIONS: Elevated serum Prx4 levels are associated with a significantly higher risk of incident CVD events or CVD mortality and all-cause mortality after adjustment for clinical risk factors. The addition of Prx4 to the FRS marginally improved risk prediction of future CVD

High blood pressure and the incidence of non-insulin dependent diabetes mellitus: Findings in A 11.5 year follow-up study in the Netherlands

To examine the contribution of cardiovascular risk factors to the development of non-insulin dependent diabetes mellitus, a prospective follow-up study was performed of a cohort, initially examined in a population survey on cardiovascular risk factors. The survey was conducted from 1975 to 1978 in the Netherlands among 5700 men and women aged 20 to 65. In 1988 a questionnaire on the prevalence of chronic diseases, including diabetes mellitus, was sent to all living participants of the initial survey. The general practitioners of the persons who indicated to have diabetes mellitus were asked to confirm the diagnosis. Diabetes mellitus was defined as current use of oral hypoglycemic drugs or insulin. After exclusion of the prevalent cases at the initial survey, 65 incident confirmed cases remained. All others responding to the questionnaire served as controls. The incidence of diabetes mellitus was associated with body mass index, use of diuretics, systolic and diastolic blood pressure. After adjustment for age and body mass index systolic and diastolic blood pressure were still associated with the incidence of non-insulin dependent diabetes mellitus in men; relative risks 1.28 (95% confidence interval 1.06-1.54) and 1.40 (95% CI 1.06-1.85) per 10 mmHg respectively. For women, only the relative risk associated with the use of diuretics remained statistically significant (2.26, 95% CI 1.04-4.90). This probably reflects the risk of (treated) hypertension: adjusted for blood pressure, the relative risk lost statistical significance. These findings suggest that elevated blood pressure is a risk for the development of non-insulin dependent diabetes mellitus (NIDDM). This supports the view that NIDDM and hypertension may have a similar origin