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 relation of fasting and 2-h postchallenge plasma glucose concentrations to mortality: data from the Baltimore Longitudinal Study of Aging with a critical review of the literature.

OBJECTIVE: Under the auspices of the National Institutes of Health, American Diabetes Association, and World Health Organization, expert committees lowered the fasting plasma glucose (FPG) concentration diagnostic for diabetes from 7.8 to 7.0 mmol/l and defined 6.1-6.9 mmol/l as impaired fasting glucose (IFG) and <6.1 mmol/l as normal fasting glucose. In 2003, IFG was lowered to 5.6-6.9 mmol/l and normal fasting glucose to <5.6 mmol/l. Reports of the relationship between glucose concentration and all-cause mortality have been inconsistent. It is not known if the 2-h plasma glucose (2hPG) concentration from an oral glucose tolerance test (OGTT) adds to the predictive power of FPG. RESEARCH DESIGN AND METHODS: We followed 1,236 men for an average of 13.4 years to determine the relationship between both FPG and 2hPG and all-cause mortality. RESULTS: Risk for mortality did not increase until the FPG exceeded 6.1 mmol/l. Risk increased by approximately 40% in the 6.1-6.9 mmol/l range and doubled when FPG ranged from 7.0 to 7.7 mmol/l. A combination of the 2hPG and FPG allowed better estimation of risk than the FPG alone. Within any category of FPG, risk generally increased as the 2hPG increased, and within any category of 2hPG, risk generally increased as the FPG increased. CONCLUSIONS: These data support the decision to lower the FPG diagnostic for diabetes from 7.8 to 7.0 mmol/l, show that both IFG and impaired glucose tolerance have risks between the normal and diabetic ranges, and show that the OGTT adds predictive power to that of FPG alone and should not be abandoned. The lowering of IFG to 5.6 mmol/l from 6.1 mmol/l, at least for mortality, is, however, not supported by our results.

The natural history of progression from normal glucose tolerance to type 2 diabetes in the Baltimore Longitudinal Study of Aging.

The natural history of progression from normal glucose tolerance (NGT) to impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and type 2 diabetes is not well defined. We studied this progression using biennial oral glucose tolerance tests performed in the Baltimore Longitudinal Study of Aging and survival analysis to assess progression from NGT to abnormal fasting plasma glucose (FPG; > or =6.1 mmol/l), abnormal 2-h plasma glucose (2hPG; > or =7.8 mmol/l), IFG (FPG 6.1-6.9 mmol/l, 2hPG < or =7.8 mmol/l), and IGT (FPG <6.1 mmol/l, 2hPG 7.8-11.0 mmol/l), and from IFG-IGT to diabetes (FPG > or =7.0 mmol/l or 2hPG > or =11.1 mmol/l). At baseline, the 815 subjects had a mean age of 57 years, 35% were women, and 60% had NGT. Of the 488 subjects with NGT, over half were followed for at least 10 years. By 10 years, 14% had progressed to abnormal FPG and 48% to abnormal 2hPG. Of the 267 subjects who progressed to IFG-IGT, 216 had additional follow-up. By 10 years, 8% of these progressed to diabetes by FPG whereas 27% progressed by 2hPG. In subsidiary analyses, we defined "abnormal" FPG as > or =5.55 mmol/l and "diabetic" FPG as > or =6.1 mmol/l, making the baseline prevalence of IFG similar to that of IGT. By these criteria, 43% progressed to abnormal FPG and 43% to abnormal 2hPG by 10 years of follow-up; among subjects developing impaired FPG or 2hPG, 22% progressed to diabetes by FPG whereas 17% progressed by 2hPG at 10 years. Nonetheless, 42% of subjects developing abnormal FPG did not develop abnormal 2hPG, and vice versa. We conclude that, although phenotypic differences in rates of progression are partly a function of diagnostic thresholds, fasting and postchallenge hyperglycemia may represent phenotypes with distinct natural histories in the evolution of type 2 diabetes.

Impaired glucose tolerance, but not impaired fasting glucose, is associated with increased levels of coronary heart disease risk factors: results from the Baltimore Longitudinal Study on Aging.

Impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) identify individuals at high risk for progression to diabetes. Whether IFG and IGT have comparable coronary heart disease (CHD) risk factor profiles, independent of their progression to diabetes, is unclear. We determined CHD risk factor levels in 937 nondiabetic individuals at baseline and biannually over a mean follow-up period of 9.5 years. Subjects had no known CHD at baseline and had > or =2 (mean 4.2) oral glucose tolerance tests during follow-up. We classified glucose tolerance categories using American Diabetes Association diagnostic criteria or modified criteria that redefined IFG as 100-126 mg/dl, creating a similar baseline prevalence of IFG and IGT. Subjects who developed diabetes during follow-up were excluded from our analysis. Baseline CHD risk factors were similar in subjects with normal glucose tolerance (NGT) and IFG, but significantly more atherogenic in those with IGT or IFG + IGT. These findings were unchanged when the modified criteria were used, suggesting that IGT is phenotypically different from IFG and is associated with increased levels of CHD risk factors. Subjects with isolated IFG had similar levels of CHD risk factors as NGT subjects, even when IFG was redefined with a lower threshold. Although CHD risk factors were increased in the IGT group, the incidence of CHD events was not significantly different among groups, perhaps owing to the limited number of events. The differences in CHD risk factors among prediabetic groups may have clinical implications for screening strategies and CHD risk stratification of individuals with IFG and IGT.

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.

Contribution of impaired glucose tolerance in subjects with the metabolic syndrome: Baltimore Longitudinal Study of Aging.

BACKGROUND: In addition to fasting plasma glucose (FPG), we examined the contribution of the oral glucose tolerance test (OGTT) in the prevalence of subjects with the metabolic syndrome (MS). METHODS AND RESULTS: Study participants were white adults in the Baltimore Longitudinal Study of Aging who underwent a fasting 2-hour OGTT. In men between the ages of 20 to 39, 40 to 59, 60 to 79, and 80 to 95 years, the prevalence of the MS by Adult Treatment Panel (ATP) III criteria (which excludes OGTT) was 11%, 28%, 32%, and 15%, respectively; whereas in women the prevalence was 5%, 12%, 24%, and 16%, respectively. If the current ATPIII dysglycemia criteria also included a 2-hour postchallenge glucose (2hPG) of 7.8 mmol/L or higher, the prevalence of the MS increased from 25% to 33% in men and from 15% to 21% in women (P<.0001). In study participants with FPG less than 5.6 mmol/L, the prevalence of the MS increased from 16% to 23% in men and from 9% to 13% in women. In men between the ages of 20 to 39, 40 to 59, 60 to 79, and 80 to 95 years and FPG less than 5.6 mmol/L, the prevalence of the MS increased to 15%, 32%, 40%, and 29%, respectively (P<.005 for men between 40 and 95 years of age), with inclusion of an abnormal 2hPG. In women between the ages of 20 to 39, 40 to 59, 60 to 79, and 80 to 95 years and FPG less than 5.6 mmol/L, the prevalence of the MS increased to 7%, 14%, 33%, and 31%, respectively, with inclusion of an abnormal 2hPG (P<.001 for women between 60 and 95 years of age). CONCLUSION: The prevalence of the MS is significantly underestimated when the current ATPIII criteria of FPG 6.1 mmol/L or higher is the only determinant of dysglycemia.

Elevated plasma glucose-dependent insulinotropic polypeptide associates with hyperinsulinemia in impaired glucose tolerance.

OBJECTIVE: The role of gut-derived incretin, glucose-dependent insulinotropic polypeptide (also known as gastric inhibitory peptide [GIP]), in compensatory beta-cell hypersecretion during insulin-resistant states and in transition to beta-cell failure in type 2 diabetes is unknown. RESEARCH DESIGN AND METHODS: We carried out oral glucose tolerance testing followed by blood sampling 10 times for 2 h on 68 age- and BMI-matched participants of the Baltimore Longitudinal Study on Aging (BLSA) with normal glucose tolerance (34 subjects), impaired glucose tolerance (IGT) (18 subjects with both impaired fasting and 2-h plasma glucose levels), and type 2 diabetes (16 subjects with both diabetic fasting and 2-h plasma glucose levels). We assayed plasma glucose, insulin, C-peptide, glucagon, and intact and total GIP levels and quantitated glucose and hormone responses to the oral glucose tolerance test. We also compared GIP and insulin release and sensitivity indexes between groups. RESULTS: After glucose ingestion, subjects with IGT had both hyperinsulinemia and hyperemia, while subjects with type 2 diabetes had both beta- and GIP-cell deficiency. In the former group, there was also a significant positive correlation between the augmented plasma intact and total GIP levels and both fasting and post-oral glucose load plasma insulin levels. CONCLUSIONS: Elevated plasma GIP levels are correlated with hyperinsulinemia in the impaired glucose-tolerant state, whereas type 2 diabetes is associated with a failure to secrete adequate amounts of both GIP and insulin, indicating a common pathway of resistance to and eventually failure of glucose responsiveness in beta- and GIP-cells.

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.

High-dose isoflavones do not improve metabolic and inflammatory parameters in androgen-deprived men with prostate cancer.

The profound hypogonadism that occurs with androgen deprivation therapy (ADT) for prostate cancer (PCa) results in complications such as diabetes and metabolic syndrome that predispose to cardiovascular disease. Because phytoestrogens have been associated with an improvement in metabolic parameters, we evaluated their role in men undergoing ADT. Our objective was to evaluate the effects of high-dose isoflavones on metabolic and inflammatory parameters in men undergoing ADT. This was a randomized, double-blind, placebo-controlled, 12-week pilot study. Participants were randomly assigned to receive 20 g of soy protein containing 160 mg of total isoflavones vs taste-matched placebo (20 g whole milk protein). The study was conducted at a tertiary care center in the United States. Thirty-three men (isoflavones = 17, placebo = 16) undergoing ADT for PCa completed this pilot study. Mean age in the 2 groups was 69 years and the majority of men were Caucasians. Mean duration of ADT in both groups was approximately 2 years (P = .70). The 2 groups were well matched at baseline. After 12 weeks of intervention, there was no significant difference in either metabolic or inflammatory parameters between the 2 groups. We found that high-dose isoflavones over a course of 12 weeks do not improve metabolic or inflammatory parameters in androgen-deprived men.

Is longitudinal pulse pressure a better predictor of 24-hour urinary albumin excretion than other indices of blood pressure?

The strong relationship between urinary albumin excretion (UAE) and pulse pressure (PP) in cross-sectional studies suggests that pressure pulsatility may contribute to renal microvascular injury. The longitudinal relationships between UAE and the various indices of blood pressure (BP) are not well studied. We compared the associations of UAE with the longitudinal exposure to PP and systolic, diastolic, and mean BPs. UAE was measured from 24-hour urine collections in 450 community-dwelling subjects (age: 57+/-15 years, 53% women, all with UAE <200 microg/min). For each subject, longitudinal indices of BP were estimated by dividing the area under the curve of serial measurements of BP (median: 5) during 1 to 22 years preceding UAE measurement by the number of follow-up years. Median (interquartile range) UAE was 4.7 microg/min (3.3 to 7.8 microg/min) in women and 5.2 microg/min (3.7 to 9.8 microg/min) in men. In women, UAE was not related to longitudinal indices of BP. In men, in multivariable-adjusted models that included either longitudinal systolic and diastolic BPs or longitudinal PP and mean BP, UAE was independently associated with systolic (standardized regression coefficient [beta]=0.227; P=0.03) but not with diastolic (beta=-0.049; P=0.59) BP and with PP (beta=0.216; P=0.01) but not with mean BP (beta=0.032; P=0.72). Comparisons of these 2 models and stepwise regression analyses both indicated that, of the 4 longitudinal indices of BP, PP was the strongest predictor of UAE in men. The pulsatile component of BP confers the highest risk for BP-induced renal microvascular injury. Future studies should examine whether PP reduction provides additional renoprotection beyond that attained by conventional BP goals alone.

Effects of high-dose isoflavones on metabolic and inflammatory markers in healthy postmenopausal women.

OBJECTIVE: After menopause, women experience changes in body composition, especially an increase in fat mass. In addition, advancing age, decreased physical activity, and increased inflammation may predispose them to develop type 2 diabetes. Isoflavones have been shown to improve metabolic parameters in postmenopausal women. However, the effect of isoflavones on adipokines/cytokines remains unclear. The purpose of this study was to evaluate the effect of high-dose isoflavones on inflammatory and metabolic markers in postmenopausal women. METHODS: We measured glucose, insulin, and adipokines/cytokines in 75 healthy postmenopausal women who were randomized to receive 20 g of soy protein with 160 mg of total isoflavones (64 mg genistein, 63 mg daidzein, and 34 mg glycitein) or 20 g of soy protein placebo for 12 weeks. Women taking estrogen discontinued therapy at least 3 months before the study. The supplements were given in a powder form and consumed once daily with milk or other beverages. RESULTS: Mean ages in the placebo and active groups were similar (P = 0.4). Average time since menopause was 9 years, and two thirds of the women underwent natural menopause. There was no significant difference in body mass index at baseline between the groups (placebo, 25.1 kg/m; active, 26 kg/m) and it did not change significantly during the study. At baseline, the placebo group had significantly higher levels of tumor necrosis factor alpha (P < 0.0001); otherwise, there was no difference in any other parameter. After 12 weeks of treatment, there were significant positive changes in tumor necrosis factor alpha levels within the placebo group (P < 0.0001) and adiponectin levels within the isoflavone group (P = 0.03). Comparison of pre-post change between the groups showed a small but significant increase in serum adiponectin levels in the isoflavone group (P = 0.03) compared with the placebo group. No significant changes were seen in any other parameter between the two groups. CONCLUSIONS: Healthy, normal-weight postmenopausal women may not experience improvement in metabolic parameters when given high-dose isoflavones despite an increase in serum adiponectin levels. The role of isoflavones in obese and insulin-resistant postmenopausal women needs exploration.

Pulse wave velocity is an independent predictor of the longitudinal increase in systolic blood pressure and of incident hypertension in the Baltimore Longitudinal Study of Aging.

OBJECTIVES: This study sought to evaluate whether pulse wave velocity (PWV), a noninvasive index of arterial stiffness, is a predictor of the longitudinal changes in systolic blood pressure (SBP) and of incident hypertension. BACKGROUND: Although arterial stiffness is believed to underlie, in part, the age-associated changes in SBP, particularly at older ages, few longitudinal studies in humans have examined the relationship between arterial stiffness and blood pressure. METHODS: Pulse wave velocity was measured at baseline in 449 normotensive or untreated hypertensive volunteers (age 53 +/- 17 years). Repeated measurements of blood pressure were performed during an average follow-up of 4.9 +/- 2.5 years. RESULTS: After adjusting for covariates including age, body mass index, and mean arterial pressure, linear mixed effects regression models showed that PWV was an independent determinant of the longitudinal increase in SBP (p = 0.003 for the interaction term with time). In a subset of 306 subjects who were normotensive at baseline, hypertension developed in 105 (34%) during a median follow-up of 4.3 years (range 2 to 12 years). By stepwise Cox proportional hazards models, PWV was an independent predictor of incident hypertension (hazard ratio 1.10 per 1 m/s increase in PWV, 95% confidence interval 1.00 to 1.30, p = 0.03) in individuals with a follow-up duration greater than the median. CONCLUSIONS: Pulse wave velocity is an independent predictor of the longitudinal increase in SBP and of incident hypertension. This suggests that PWV could help identify normotensive individuals who should be targeted for the implementation of interventions aimed at preventing or delaying the progression of subclinical arterial stiffening and the onset of hypertension.

Ubiquitination is involved in glucose-mediated downregulation of GIP receptors in islets.

Glucose-dependent insulinotropic polypeptide (GIP) is a gastrointestinal hormone that has a potent stimulatory effect on insulin release under conditions of normal glucose tolerance. However, its insulinotropic effect is reduced or even absent entirely in type 2 diabetic patients. In this study, we addressed the role of glucose concentration in the diabetic range of >or=11 mM, i.e., hyperglycemia per se, as a cause of the lack of response to GIP. Culturing rat and human pancreatic islets in >or=11 mM glucose for up to 24 h resulted in prevention of GIP-mediated intracellular cAMP increase compared with culturing in 5 mM glucose. Western blot analysis revealed a selective 67 +/- 2% (rat) and 60 +/- 8% (human) decrease of GIP-R expression in islets exposed to >or=11 mM glucose compared with 5 mM glucose (P < 0.001). We further immunoprecipitated GIP-R from islets and found that GIP-R was targeted for ubiquitination in a glucose- and time-dependent manner. Downregulation of GIP-R was rescued by treating isolated islets with proteasomal inhibitors lactacystin and MG-132, and the islets were once again capable of increasing intracellular cAMP levels in response to GIP. These results suggest that the GIP-R is ubiquitated, resulting in downregulation of the actions of GIP.

Hyperglycemia and insulin resistance in men with prostate carcinoma who receive androgen-deprivation therapy.

BACKGROUND: Prostate carcinoma (PCa) is one of the most common malignancies in men. Androgen-deprivation therapy (ADT) is used frequently in the treatment of recurrent and metastatic PCa, rendering these men hypogonadal. Because male hypogonadism is associated with an unfavorable metabolic profile, and men with PCa have high cardiovascular mortality, the authors evaluated the effects of long-term ADT on fasting glucose levels, insulin levels, and insulin resistance. METHODS: To evaluate the long-term effects of ADT on fasting glucose and insulin resistance in men with PCa who received ADT and to determine whether these metabolic alterations are a result of hypogonadism, the authors conducted a cross-sectional study at a university-based research institution in the United States. In total, 53 men were evaluated, including 18 men with PCa who received ADT for at least 12 months prior to the onset of the study (the ADT group), 17 age-matched men with nonmetastatic PCa who had undergone prostatectomy and/or received radiotherapy and who were not receiving ADT (the non-ADT group), and 18 age-matched controls (the control group). None of the men had a known history of diabetes mellitus. RESULTS: The mean age was similar in all 3 groups (P=0.33). Serum total testosterone levels (P<0.0001) and free testosterone levels (P<0.0001) were significantly lower in the ADT group compared with the other groups. Men in the ADT group had a higher BMI compared with the other groups (overall P=0.005). After adjustment for age and BMI, men in the ADT group had significantly higher fasting levels of the following parameters: 1) Glucose levels were 131.0+/-7.43 mg/dL in the ADT group compared with 103.0+/-7.42 mg/dL in the non-ADT group (P=0.01) and 99.0+/-7.58 mg/dL in the control group (P<0.01). 2) Insulin levels were 45.0+/-7.25 uU/mL in the ADT group compared with 24.0+/-7.24 uU/mL in the non-ADT group (P=0.05) and 19.0+/-7.39 uU/mL in the control group (P=0.02). 3) Leptin levels were 25.0+/-2.57 ng/mL in the ADT group compared with 12.0+/-2.56 ng/mL in the non-ADT group (P<0.01) and 6.0+/-2.62 ng/mL in the control group (P<0.01). 4) The homeostatic model assessment for insulin resistance (HOMAIR)=17.0+/-2.78 in the ADT group compared with HOMAIR=6.0+/-2.77 in the non-ADT group (P<0.01) and HOMAIR=5.0+/-2.83 in the control group (P=0.01). There was a significant negative correlation between total and free testosterone levels with fasting glucose, insulin, leptin, and HOMAIR. CONCLUSIONS: The current data suggested that men with PCa who are receiving long-term ADT are at risk for developing insulin resistance and hyperglycemia, thus leading to their increased risk of cardiovascular disease. This adverse metabolic profile developed independent of age and BMI and appeared to be a direct result of androgen deprivation.

Metabolic syndrome in men with prostate cancer undergoing long-term androgen-deprivation therapy.

PURPOSE: Prostate cancer (PCa) is one of the most common cancers in men. Men with recurrent or metastatic PCa are treated with androgen-deprivation therapy (ADT), resulting in profound hypogonadism. Because male hypogonadism is a risk factor for metabolic syndrome and men with PCa have high cardiovascular mortality, we evaluated the prevalence of metabolic syndrome in men undergoing long-term ADT. PATIENTS AND METHODS: This was a cross-sectional study. We evaluated 58 men, including 20 with PCa undergoing ADT for at least 12 months (ADT group), 18 age-matched men with nonmetastatic PCa who had received local treatment and were recently found to have an increasing prostate-specific antigen (non-ADT group), and 20 age-matched controls (control group). Men in the non-ADT and control groups were eugonadal. Metabolic syndrome was defined according to the Adult Treatment Panel III criteria. RESULTS: Mean age was similar among the groups. Men on ADT had significantly higher body mass index and lower total and free testosterone levels. The prevalence of metabolic syndrome was higher in the ADT group compared with the non-ADT (P < .01) and control (P = .03) groups. Among the components of metabolic syndrome, men on ADT had a higher prevalence of abdominal obesity and hyperglycemia. Androgen-deprived men also had elevated triglycerides compared with controls (P = .02). The prevalence of hypertension and low high-density lipoprotein levels were similar. CONCLUSION: These data suggest that metabolic syndrome was present in more than 50% of the men undergoing long-term ADT, predisposing them to higher cardiovascular risk. Abdominal obesity and hyperglycemia were responsible for this higher prevalence. We recommend prospective studies to further delineate this association.

Serum vitamin levels and the risk of asthma in children.

Dietary intake, especially of antioxidant vitamins A, C, E, and the carotenoids, has been linked with the presence and severity of asthma. From the Third National Health and Nutrition Examination Survey (NHANES III), conducted in the United States between 1988 and 1994, the authors selected 4,093 children (aged 6-17 years) for whom relevant medical, socioeconomic, and anthropometric data were complete. The children were 50.6% female, and 9.7% reported a diagnosis of asthma. Bivariate analyses showed that asthma diagnosis was associated with lower levels of serum vitamin C, alpha-carotene, beta-carotene, and beta-cryptoxanthin. However, antioxidant levels may be surrogate markers for socioeconomic variables such as race, poverty, tobacco exposure, or general nutritional status. In logistic models that included age, body mass index, socioeconomic variables, antioxidant levels, parental asthma, and household smoking, the only antioxidants significantly associated with asthma were vitamin C (odds ratio = 0.72 per mg/dl, 95% confidence interval = 0.55, 0.95) and alpha-carotene (odds ratio = 0.95 per micro g/dl, 95% confidence interval = 0.90, 0.99). The odds ratio for asthma in the highest quintile of serum vitamin C relative to the lowest was 0.65 (p < 0.05), whereas it was 0.74 for alpha-carotene (p = 0.066). The authors concluded that low vitamin C and alpha-carotene intakes are associated with asthma risk in children.

Racial difference in lung function in African-American and White children: effect of anthropometric, socioeconomic, nutritional, and environmental factors.

African-American children have lower lung volumes than White children. However, the contributions of anthropometric, socioeconomic, nutritional, and environmental factors to this difference are unknown. From participants in the Third National Health and Nutrition Examination Survey (1988-1994), the authors selected 1,462 healthy nonsmoking children (623 White and 839 African-American) aged 8-17 years. The African-American children were taller and heavier but had lower lung function. African Americans were poorer and had lower levels of the antioxidant vitamins A and C and alpha-carotene. The authors performed regression analyses using data on anthropometric, socioeconomic, and nutritional factors and smoke exposure. Adjustment for sitting height explained 42-53% of the racial difference. Socioeconomic factors and antioxidant vitamin levels accounted for an additional 7-10%. Overall, the authors could account for only 50-63% of the racial difference. Exposure to tobacco in the home was weakly associated with forced expiratory volume in 1 second in girls, accounting for 1% of the difference. In children aged 8-12 years (n = 752), birth weight explained 3-5% of the racial difference, whereas in-utero exposure to maternal smoking had no significant effect. The authors conclude that in healthy children, the major explanatory variable for the racial difference in lung function is body habitus; socioeconomic, nutritional, and environmental confounders play a smaller role.

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.