Denise von Mühlen

Vitamin D Status and Cardiometabolic Risk Factors in the United States Adolescent Population

OBJECTIVE: Evidence on the association of vitamin D with cardiovascular risk factors in youth is very limited. We examined whether low serum vitamin D levels (25-hydroxyvitamin D [25(OH)D]) are associated with cardiovascular risk factors in US adolescents aged 12 to 19 years. METHODS: We conducted a cross-sectional analysis of 3577 fasting, nonpregnant adolescents without diagnosed diabetes who participated in the 2001–2004 National Health and Nutrition Examination Survey. Cardiovascular risk factors were measured using standard methods and defined according to age-modified Adult Treatment Panel III definitions. RESULTS: Mean 25(OH)D was 24.8 ng/mL; it was lowest in black (15.5 ng/mL), intermediate in Mexican American (21.5 ng/mL), and highest in white (28.0 ng/mL) adolescents (P < .001 for each pairwise comparison). Low 25(OH)D levels were strongly associated with overweight status and abdominal obesity (P for trend < .001 for both). After adjustment for age, gender, race/ethnicity, BMI, socioeconomic status, and physical activity, 25(OH)D levels were inversely associated with systolic blood pressure (P = .02) and plasma glucose concentrations (P = .01). The adjusted odds ratio (95% confidence interval) for those in the lowest (<15 ng/mL) compared with the highest quartile (>26 ng/mL) of 25(OH)D for hypertension was 2.36 (1.33–4.19); for fasting hyperglycemia it was 2.54 (1.01–6.40); for low high-density lipoprotein cholesterol it was 1.54 (0.99–2.39); for hypertriglyceridemia it was 1.00 (0.49–2.04); and for metabolic syndrome it was 3.88 (1.57–9.58). CONCLUSIONS: Low serum vitamin D in US adolescents is strongly associated with hypertension, hyperglycemia, and metabolic syndrome, independent of adiposity.

Endogenous Levels of Dehydroepiandrosterone Sulfate, but Not Other Sex Hormones, Are Associated with Depressed Mood in Older Women: The Rancho Bernardo Study

OBJECTIVE: The purpose of this study was to determine whether endogenous steroid hormone levels are associated with depressed mood in community‐dwelling older women.

Waist circumference and testosterone levels in community dwelling men. The Tromsø study.

To examine the relationship of total and free testosterone and sex hormone-binding globulin (SHBG) with central obesity in men, we studied 1548 men aged 25–84 years that took part in the 1994–1995 survey of the Tromsø study. Total testosterone and SHBG were measured by immuno-assay and the free testosterone fraction was calculated. These measurements were analyzed in relation to anthropometric data and lifestyle factors. The age-adjusted correlation between waist circumference (WC) and total testosterone was −0.34 (p < 0.001), between WC and free testosterone −0.09 (p < 0.001) and, between WC and SHBG −0.44 (p < 0.001). Adjusting for BMI and lifestyle factors weakened, but did not eliminate these associations. All hormone and SHBG associations were stronger for WC than for waist-hip ratio or BMI. In age- and BMI-adjusted analyses men with a WC ≥ 102 cm had significantly lower levels of total testosterone and SHBG compared to men with an optimal WC, defined as < 94 cm (12.3 vs. 13.9 nmol/l; p < 0.01 and 48.5 vs. 55.1 nmol/l; p < 0.001, respectively). The lowest levels of total and free testosterone were observed in men with relatively high WC despite relatively low overall obesity (BMI), suggesting that WC should be the preferred anthropometric measurement in predicting endogenous testosterone levels.

Relation of 25-hydroxyvitamin D and parathyroid hormone levels with metabolic syndrome among US adults

OBJECTIVE Previous research on the combined association of 25-hydroxyvitamin D (25(OH)D) and parathyroid hormone (PTH) with metabolic syndrome may have been limited by restricted age variability and a lack of representation of the general population. This study examined the combined association of 25(OH)D and PTH with Adult Treatment Panel III-defined MetSyn among a nationally representative sample of US adults. DESIGN AND METHODS This population-based cross-sectional study included 834 men and 820 women aged > or =20 years without diagnosed diabetes who completed a physical examination as part of the 2003-2004 US National Health and Nutrition Examination Survey. RESULTS After adjusting for age, sex, race/ethnicity, income, lifestyle factors, total calcium, and energy intake, the odds ratio (OR) for MetSyn in the highest quintile of 25(OH)D (median 88.0 nmol/l) compared with the lowest quintile (median 26.8 nmol/l) was 0.27 (0.15, 0.46; P(trend)<0.001). This relation was unchanged after additional adjustment for PTH level (OR, 0.26; 0.15, 0.44; P(trend)<0.001) and did not differ by sex (P interaction 0.6) or age (< or > or =50 years; P interaction 0.2). In contrast, the multivariable-adjusted odds for MetSyn increased with increasing PTH among older men (P(trend) 0.004), but not younger men (P(trend) 0.4) or women regardless of age (P(trend) 0.4 in younger and older women). CONCLUSIONS These data suggest an inverse association of 25(OH)D with MetSyn, independent of potential confounding factors, calcium intake, and PTH, and a positive association of PTH with MetSyn among older men.

Serum vitamin D, parathyroid hormone levels, and carotid atherosclerosis

Evidence suggests low vitamin D and elevated parathyroid hormone (PTH) concentrations may increase risk for cardiovascular disease. However, little is known about the association between vitamin D or PTH and subclinical atherosclerosis. This cross-sectional study included 654 community-dwelling older adults aged 55-96 years (mean age, 75.5 years) without a history of coronary heart disease, revascularization, or stroke enrolled in the Rancho Bernardo Study who completed a clinic examination in 1997-1999 and provided a blood sample for determination of serum 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)(2)D], and PTH concentrations. Carotid artery intima-media wall thickness (IMT) was measured as an indicator of atherosclerosis at two sites with B-mode ultrasound. After adjusting for age, sex, smoking, alcohol intake, waist-to-hip ratio, exercise, season of blood draw, diabetes, and hypertension, geometric mean internal carotid IMT (p(trend) 0.022), but not common carotid IMT (p(trend) 0.834) decreased in a dose-dependent fashion with increasing concentration of 25(OH)D. There was no association of 1,25(OH)(2)D or PTH with either measure of carotid IMT. In subgroup analyses, 1,25(OH)(2)D was inversely associated with internal carotid IMT among those with hypertension (p for interaction 0.036). These findings from a population-based cohort of older adults suggest a potential role for vitamin D in the development of subclinical atherosclerosis. Additional research is needed to determine whether vitamin D may influence the progression of atherosclerosis, including the effects of supplementation on the atherosclerotic process.

Measures of renal function, BMD, bone loss, and osteoporotic fracture in older adults: the Rancho Bernardo study.

The association between bone and renal function in healthy seniors is not well studied. In this cross‐sectional and longitudinal study in 1713 older men and women, creatinine clearance was significantly associated with hip BMD. If confirmed, this may warrant adding mild to moderate renal dysfunction as an indication for osteoporosis screening.

A community-based study of menopause symptoms and estrogen replacement in older women

This study examines the symptoms after a natural menopause recalled by women aged 50-89 years. We determined the frequency and clustering of symptoms, the effect of age on symptoms, and the relation of symptoms to the use of estrogen therapy in a cross-sectional, community-based study of 589 Caucasian, middle- to upper-middle-class women from Rancho Bernardo, California. At the time of menopause, 55% of the women reported that they felt life was getting better and 57% were more cheerful. The most frequently recalled symptoms were hot flushes (74%), propensity to weight gain (45%), night sweats (35%), tiredness (32%), and insomnia (28%). Irritability was reported by one-fourth, depression by one-fifth. Nearly 11% reported anxiety about looking older. The recalled prevalence of hot flushes, irritability, weepiness and tiredness did not vary by current age, but younger women were significantly more likely than older women to have experienced night sweats, visible flushes, depression, anxiety about looking older and insomnia. Principal components factor analysis yielded four main independent factors: psychological symptoms (21% of the variance), vasomotor symptoms (14%), positive feelings (11%), and negative self-image (8%). The four symptom groupings suggest different causal mechanisms. Forty-two percent reported past, and 27% reported current use of estrogen therapy. Both past and current hormone users were significantly more likely to report menopause symptoms than non-users. Estrogen use was not associated with positive feelings or self-image at the time of menopause. Although three-quarters experienced symptoms, the majority of women reported positive feelings about menopause.

Differences in vitamin D status as a possible contributor to the racial disparity in peripheral arterial disease

BACKGROUND Racial differences in cardiovascular risk factors do not fully explain the higher prevalence of lower-extremity peripheral arterial disease (PAD) in black adults. OBJECTIVE We sought to determine whether any of this excess risk may be explained by vitamin D status, which has been widely documented to be lower in blacks than in whites. DESIGN This population-based cross-sectional study included 2987 white and 866 black persons aged >or=40 y from the 2001-2004 National Health and Nutrition Examination Survey. PAD was defined as an ankle-brachial pressure index of <0.90 in either leg. RESULTS Mean (+/-SEM) 25-hydroxyvitamin D [25(OH)D] concentrations were significantly lower in black than in white adults (39.2 +/- 1.0 and 63.7 +/- 1.1 nmol/L, respectively; P < 0.001). Adjusted odds ratios for PAD decreased in a dose-dependent fashion with increasing quartiles of 25(OH)D in white adults [1.00 (referent), 0.86, 0.67, and 0.53; P for trend < 0.001]. In black adults, the association was nonlinear; models with cubic splines suggested evidence of greater odds for PAD and a trend for lower odds for PAD at the lowest and highest concentrations of 25(OH)D, respectively. After adjustment for racial differences in socioeconomic status and for traditional and novel risk factors, odds for PAD in black compared with white adults were reduced from 2.11 (95% CI: 1.55, 2.87) to 1.67 (1.11, 2.51). After additional adjustment for 25(OH)D, the odds were further reduced to 1.33 (0.84, 2.10). CONCLUSIONS Racial differences in vitamin D status may explain nearly one-third of the excess risk of PAD in black compared with white adults. Additional research is needed to confirm these findings.

Leptin predicts BMD and bone resorption in older women but not older men: the Rancho Bernardo study.

We studied the relation of leptin to bone, bone loss, and bone turnover in community‐dwelling men and women. Leptin predicted higher BMD and lower bone turnover only in women. Leptin was not associated with 4‐year bone loss in either sex.

Serum uric acid levels improve prediction of incident type 2 diabetes in individuals with impaired fasting glucose: the Rancho Bernardo Study.

OBJECTIVE To determine whether serum uric acid predicts incident type 2 diabetes by glucose tolerance status in older community-dwelling adults. RESEARCH DESIGN AND METHODS Participants without diabetes at baseline were evaluated for incident type 2 diabetes 13 years later. Baseline glucose tolerance status was defined as normoglycemia, impaired fasting glucose, and impaired postchallenge glucose tolerance. RESULTS A total of 566 participants were included (mean age 63.3 ± 8.6 years; 41% men). Regression models adjusted for age, sex, BMI, diuretic use, and estimated glomerular filtration rate showed that for each 1 mg/dl increment in uric acid levels, incident type 2 diabetes risk increased by ∼60%. When analyses were stratified by glucose status, uric acid levels independently predicted incident type 2 diabetes among participants who had impaired fasting glucose (odds ratio 1.75, 95% CI 1.1–2.9, P = 0.02). CONCLUSIONS Uric acid may be a useful predictor of type 2 diabetes in older adults with impaired fasting glucose.