Aging, androgens, and the metabolic syndrome in a longitudinal study of aging.

BACKGROUND: Based on Adult Treatment Panel III criteria, we previously reported that the prevalence of the metabolic syndrome (MS) increased with aging; was higher if elevated 2-h plasma postglucose challenge values were included as a criterion; and was greater in men, compared with women. The aim of this study was to evaluate the relationship between the MS and circulating androgen levels in a cohort of men in the Baltimore Longitudinal Study of Aging. METHODS AND RESULTS: Study participants were Caucasian community-dwelling adult men in the Baltimore Longitudinal Study of Aging, who underwent a fasting 2-h oral glucose tolerance test and had serum concentrations of total testosterone (T), dehydroepiandrosterone sulfate, and SHBG levels measured. The prevalence of the MS was 4, 21, 21, and 18% for men between the ages of 20 and 39, 40 and 59, 60 and 79, and 80 and 94 yr, respectively. Total T and SHBG were inversely related to the development of the MS over a mean follow-up period of 5.8 yr (range 1.5-14.0 yr), whereas the free T index and body mass index were positively related to the incidence of the MS. Age alone did not predict the development of the MS, nor did the inclusion of abnormal 2-h plasma postglucose challenge levels in the classification of the MS. Stepwise proportional hazards regression analyses showed that among the various measurements, SHBG levels exerted the greatest influence on development of the MS. CONCLUSION: The prevalence of the MS increased with aging, and this was associated with lower androgen levels. Lower total T and SHBG predicted a higher incidence of the MS.

The combination of high fruit and vegetable and low saturated fat intakes is more protective against mortality in aging men than is either alone: the Baltimore Longitudinal Study of Aging.

Saturated fat (SF) intake contributes to the risk of coronary heart disease (CHD) mortality. Recently, the protective effects of fruit and vegetable (FV) intake on both CHD and all-cause mortality were documented. However, individuals consuming more FV may be displacing higher-fat foods. Therefore, we investigated the individual and combined effects of FV and SF consumption on total and CHD mortality among 501 initially healthy men in the Baltimore Longitudinal Study of Aging (BLSA). Over a mean 18 y of follow-up, 7-d diet records were taken at 1-7 visits. Cause of death was ascertained from death certificates, hospital records, and autopsy data. After adjustment for age, total energy intake, BMI, smoking, alcohol use, dietary supplements, and physical activity score, FV and SF intakes were individually associated with lower all-cause and CHD mortality (P < 0.05). When both FV and SF were included in the same model, associations of each were attenuated with CHD mortality, and no longer significant for all-cause mortality. Men consuming the combination of > or =5 servings of FV/d and < or =12% energy from SF were 31% less likely to die of any cause (P < 0.05), and 76% less likely to die from CHD (P < 0.001), relative to those consuming < 5 FV and >12% SF. Men consuming either low SF or high FV, but not both, did not have a significantly lower risk of total mortality; but did have 64-67% lower risk of CHD mortality (P < 0.05) relative to those doing neither. These results confirm the protective effects of low SF and high FV intake against CHD mortality. In addition, they extend these findings by demonstrating that the combination of both behaviors is more protective than either alone, suggesting that their beneficial effects are mediated by different mechanisms.

Metabolic syndrome amplifies the age-associated increases in vascular thickness and stiffness.

OBJECTIVES: We sought to evaluate whether the clustering of multiple components of the metabolic syndrome (MS) has a greater impact on these vascular parameters than individual components of MS. BACKGROUND: Intima-media thickness (IMT) and vascular stiffness have been shown to be independent predictors of adverse cardiovascular events. The MS is defined as the clustering of three or more of the cardiovascular risk factors of dysglycemia, hypertension, dyslipidemia, and obesity. METHODS: Carotid IMT and stiffness were derived via B-mode ultrasonography in 471 participants from the Baltimore Longitudinal Study on Aging, who were without clinical cardiovascular disease and not receiving antihypertensive therapy. RESULTS: The MS conferred a disproportionate increase in carotid IMT (+16%, p < 0.0001) and stiffness (+32%, p < 0.0001), compared with control subjects. Multiple regression models, which included age, gender, smoking, low-density lipoprotein, as well as each individual component of MS as continuous variables, showed that MS was an independent determinant of both IMT (p = 0.002) and stiffness (p = 0.012). The MS was associated with a greater prevalence of subjects whose values were in the highest quartiles of IMT, stiffness, or both. CONCLUSIONS: Even after taking into account each individual component of MS, the clustering of at least three of these components is independently associated with increased IMT and stiffness. This suggests that the components of MS interact to synergistically impact vascular thickness and stiffness. Future studies should examine whether the excess cardiovascular risk associated with MS is partly mediated through the amplified alterations in these vascular properties.

Association of prostate cancer risk with insulin, glucose, and anthropometry in the Baltimore longitudinal study of aging.

OBJECTIVES: To examine the relationship of insulin, glucose, and anthropometry with the subsequent risk of prostate cancer. METHODS: The relative risk of prostate cancer by insulin, glucose, and anthropometric measures was evaluated in 823 male participants (87 patients with prostate cancer in 10,737 person-years of follow-up) of the Baltimore Longitudinal Study of Aging who had at least one fasting plasma insulin measurement, which was prediagnostic for those with prostate cancer. Age-adjusted and multivariate-adjusted relative risks were estimated from Cox proportional hazards regression models. RESULTS: Insulin concentrations were in the normal range (defined as less than 20 microU/mL) for 95.1% of participants. Fasting insulin and glucose levels were unrelated to prostate cancer risk in our overall analysis (P for trend = 0.56 and 0.45, respectively). The relative risk of prostate cancer for the second through fourth quartiles of the waist/hip ratio compared with the lowest quartile was 2.10, 1.96, and 2.06, respectively (P for trend = 0.32). Risk was unrelated to waist circumference and body mass index. CONCLUSIONS: The results of this study do not conclusively support positive associations of markers of insulin and glucose metabolism and obesity with prostate cancer. Additional larger prospective studies with repeated measure of these parameters are warranted to explore these associations further.

Glucose tolerance, glucose utilization and insulin secretion in ageing.

Ageing is associated with an increased incidence of hypertension, macrovascular disease and type 2 diabetes (non-insulin-dependent diabetes). It has been suggested that a common mechanism may be responsible for all of these pathological states since all of these conditions often cluster in the same individual. Epidemiological and clinical data have consistently demonstrated an association between insulin resistance and/or hyperinsulinaemia and glucose intolerance, dyslipidaemia and elevated systolic blood pressures. Therefore, insulin resistance and hyperinsulinaemia have been proposed as the causal link among the elements of the clusters. The elderly are more glucose intolerant and insulin resistant, but it remains controversial whether this decrease in function is due to an inevitable consequence of 'biological ageing' or due to environmental or lifestyle variables, noticeably increased adiposity/altered fat distribution and physical inactivity. An increase of these modifiable factors has been shown to result in increases in insulin resistance and hyperinsulinaemia and vice versa. However, insulin secretion appears to decrease with age even after adjustments for differences in adiposity, fat distribution and physical activity. The glucose intolerance of ageing may be due, in part, to decreased insulin sensitivity of pancreatic / cells to insulinotropic gut hormones (GLP1/GIP) and in part to alterations of hepatic glucose production.