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Biomedical subjects

R E Van Pelt

Publications and source records attributed to R E Van Pelt.

14 recordsLinked to original sources

Lower-body adiposity and metabolic protection in postmenopausal women.

CONTEXT: It has been suggested that the propensity to store fat in the gluteal-femoral region may be cardioprotective. OBJECTIVE: The primary aim of this study was to test whether the favorable associations of leg fat with risk factors for cardiovascular disease persist after controlling for the highly unfavorable effects of abdominal (visceral or sc) adiposity in postmenopausal women. STUDY PARTICIPANTS: The study included 95 postmenopausal women [age, 60 +/- 8 yr (mean +/- SD)]. MAIN OUTCOMES: Whole-body and regional fat distribution was measured using dual-energy x-ray absorptiometry and abdominal computed tomography. Markers of insulin resistance and dyslipidemia were determined from oral glucose tolerance tests and fasted lipid and lipoprotein measurements, respectively. Primary outcomes were: fasting insulin (INS0), area under the insulin curve (INS(AUC)), product of the oral glucose tolerance test insulin and glucose AUC (INS(AUC) - GLU(AUC)), serum triglycerides (TG), and high-density lipoprotein (HDL) cholesterol. RESULTS: Controlling for trunk fat revealed a favorable effect of leg fat on INS0, INS(AUC), INS(AUC) x GLU(AUC), TG, and HDL. However, after controlling for either visceral or sc abdominal adiposity, TG was the only risk factor for which the favorable effect of leg fat persisted. CONCLUSIONS: The lack of an association between leg fat and most of the risk factors, after adjusting for abdominal visceral or sc fat, suggests an overriding deleterious influence of abdominal adiposity on cardiovascular risk. Nevertheless, our finding that regional adipose tissue depots have apparent independent and opposing effects on serum TG supports the need for further research into the physiological mechanisms governing these effects.

Abdomen↗

Protection of bone mass by estrogens and raloxifene during exercise-induced weight Loss.

The aim of this study was to determine whether estrogen and/or raloxifene help to conserve bone mineral density (BMD) during moderate weight loss. Postmenopausal women (n = 68) participated in a 6-month weight loss program that consisted primarily of supervised exercise training. Another 26 women were studied over 6 months of weight stability. All participants were randomized to three treatment arms: placebo, raloxifene (60 mg/d), or hormone therapy (HT; conjugated estrogens, 0.625 mg/d; trimonthly medroxyprogesterone acetate, 5 mg/d for 13 d, for women with a uterus). Changes in body weight (mean +/- se) averaged 0.8 +/- 0.5 kg in the weight-stable group and -4.1 +/- 0.4 kg in the weight loss group. Across all measured skeletal sites, average changes in BMD in weight stable women were -0.6 +/- 1.1% (n = 7), 0.9 +/- 0.6% (n = 9), and 3.0 +/- 0.7% (n = 10) in the placebo, raloxifene, and HT groups, respectively; comparable BMD changes in the weight loss groups were -1.5 +/- 0.5% (n = 22), -0.5 +/- 0.5% (n = 23), and 1.1 +/- 0.4% (n = 23). There were no significant interactions between weight loss and drug treatment on changes in BMD, but there were significant main effects of weight loss on lumbar spine (P = 0.022), total hip (P = 0.010), and trochanter BMD (P < 0.001). These findings suggest that weight loss, even when modest in magnitude and induced by exercise training, causes a reduction in BMD, particularly in women not taking raloxifene or HT. It is not known whether reductions in BMD of this magnitude increase the risk for osteoporotic fracture.

Aged↗

Intravenous estrogens increase insulin clearance and action in postmenopausal women.

To test the hypothesis that estrogens alter insulin action, we evaluated the effects of intravenous conjugated estrogens (CE) on insulin-stimulated steady-state glucose infusion rate (SSGIR) and suppression of plasma glycerol in postmenopausal women (mean +/- SD; 56 +/- 4 yr; n = 12) not using hormone replacement. SSGIR and glycerol were measured during a two-stage (8 and 40 mU. m-2. min-1) hyperinsulinemic euglycemic clamp on 2 days, with or without a 2.5-mg intravenous CE bolus. Serum estradiol concentrations were increased approximately 200% on the estrogen (EST) compared with the control (CON) days. Serum insulin was reduced (P < 0.01) during stage 2 of the clamp for EST (63.3 +/- 12.8 micro U/ml) vs. CON (78.2 +/- 15.8 micro U/ml). Mean SSGIR and plasma glycerol did not differ between CON and EST days. With adjustment for differences in insulin concentration between conditions, stage 2 glucose disposals were significantly higher (8.63 vs. 7.20 mg. kg-1. min-1) and plasma glycerol concentrations were significantly lower (29.4 vs. 35.0 micro mol/l) for EST vs. CON. Our findings suggest that acute CE administration increases insulin clearance and action in postmenopausal women.

Body Composition↗

Effects of estrogen replacement on metabolic factors that influence physical performance in female hypogonadism.

There is a lack of knowledge regarding the effects of estrogens on physical performance. This is related, in part, to the challenge of isolating the effects of estrogens from those of progestins, because levels of both hormones fluctuate across the menstrual cycle, both decline during the menopausal transition, and the administration oh hormones to hypogonadal women typically involves a combination of estrogens and progestins. Some research findings suggest that fluctuations in estrogen levels acutely influence factors that may affect physical performance, such as substrate utilization or maximal aerobic power, but solid evidence is lacking. The simple observation that hypogonadism is not uncommon among elite athletes in some sports suggests that estrogen deficiency does not have a major negative impact on athletic performance. However, chronic hypogonadism may ultimately lead to impaired performance by menas that are not necessarily obvious. For example, chronic estrogen deficiency has potent, deleterious effects on the skeleton that can increase risk for stress fracture and may limit the ability to sustain a high level of physical training. Estrogen deficiency also appears to promote fat accumulation and may accelerate the loss of fat-free mass, and both of these changes in body composition could impair physical performance. There is evidence that hormone replacement attenuates the negative effects of hypogonadism on body composition and bone density, and that effects are mediated primarily by estrogens rather than progestins. Further research is necessary to broaden the understanding of the role of the estrogens in physical performance.

Adult↗

Contributions of total and regional fat mass to risk for cardiovascular disease in older women.

The aim of this study was to determine whether trunk fat mass, measured by dual-energy X-ray absorptiometry (DEXA), is predictive of insulin resistance and dyslipidemia, independently of arm and leg fat mass, in postmenopausal women. Total and regional body composition was measured by DEXA in 166 healthy, postmenopausal women (66 +/- 4 yr). Four primary markers of insulin resistance and dyslipidemia were assessed: 1) area under the curve for the insulin (INS(AUC)) response to an oral glucose tolerance test (OGTT), 2) product of the OGTT glucose and insulin areas (INS(AUC)xGLU(AUC)), 3) serum triglycerides (TG), and 4) high-density lipoprotein (HDL)-cholesterol. Trunk fat mass was the strongest independent predictor of each of the primary dependent variables. In multivariate regression models, trunk fat mass was associated with unfavorable levels of INS(AUC), INS(AUC)xGLU(AUC), TG, and HDL-C, whereas leg fat mass was favorably associated with each of these variables. Thus trunk fat is a strong independent predictor of insulin resistance and dyslipidemia in postmenopausal women, whereas leg fat appears to confer protective effects against metabolic dysfunction.

Abdomen↗

Waist circumference vs body mass index for prediction of disease risk in postmenopausal women.

OBJECTIVE: To test the sensitivity of waist circumference (central adiposity) as an index of disease risk in postmenopausal women. DESIGN: Retrospective analysis of postmenopausal women tested at Washington University School of Medicine. SUBJECTS: A total of 323 healthy postmenopausal (66+/-5 y; mean+/-s.d.) women not using any hormone replacement. MEASUREMENTS: Body composition, hyperinsulinemia (insulin area), triglycerides and HDL-cholesterol. RESULTS: Excess waist size had a stronger association with hyperinsulinemia and hypertriglyceridemia than body mass index (BMI; kg/m(2)) in otherwise healthy, postmenopausal women. After adjusting for BMI, a strong relation existed between waist circumference and insulin area, HDL-cholesterol and triglycerides (P<0.01). Conversely, after adjusting for waist circumference, no relation was apparent between BMI and the dependent variables of interest. The strength of the association between waist circumference and disease risk became most apparent when analyses were restricted to normal-weight women (BMI 24--28 kg/m(2)). When BMI was held constant, hyperinsulinemia and triglyceridemia increased dose-dependently with changes in waist size. CONCLUSION: Waist circumference, an easily obtained index of central adiposity, is a more sensitive measure of relative disease risk than is BMI in middle-aged and older women, particularly in normal-weight individuals.

Adipose Tissue↗

Effects of HRT and exercise training on insulin action, glucose tolerance, and body composition in older women.

The independent and combined effects of exercise training and hormone replacement therapy (HRT) on body composition, fat distribution, glucose tolerance, and insulin action were studied in postmenopausal women, aged 68 +/- 5 yr, assigned to control (n = 19), exercise (n = 18), HRT (n = 15), and exercise + HRT (n = 16) groups. The exercise consisted of 2 mo of flexibility exercises followed by 9 mo of endurance exercise. HRT was conjugated estrogens 0.625 mg/day and trimonthly medroxyprogesterone acetate 5 mg/day for 13 days. Total and regional body composition were measured by dual-energy X-ray absorptiometry. Serum glucose and insulin responses were measured during a 2-h oral glucose tolerance test. There were significant main effects of exercise on reductions in total and regional (trunk, arms, legs) fat mass, increase in leg fat-free mass, and improvements in glucose tolerance and insulin action. There were significant main effects of HRT on the reduction of total fat mass (HRT, -3.0 +/- 4.0 kg; no HRT, -1.3 +/- 2.6 kg), with a strong trend for reductions in trunk and leg fat mass (both P = 0.07). There was also a significant improvement in insulin action in response to HRT. These results suggest that there are independent and additive effects of exercise training and HRT on the reduction in fat mass and improvement in insulin action in postmenopausal women; the effect of HRT on insulin action may be mediated, in part, through changes in central adiposity.

Adipose Tissue↗

Acute exercise effect on postabsorptive serum leptin.

We postulated that high circulating cortisol levels during intense exercise would lead to increased serum leptin concentrations. Young, lean men ate a small meal and then exercised on a cycle ergometer for 41 min or rested on a control day. Serum leptin concentration was 10% greater during exercise than in the control condition (P < 0.05). Directly after exercise, serum leptin dropped to approximately 10% less than the control level (P < 0.05) but had recovered to the nonexercised level after approximately 2 h of recovery. Rapid exercise effects on circulating leptin were related to changes in hemoconcentration rather than changes in leptin mass. When serum leptin was normalized to serum protein, leptin increased by 10% in the exercise condition compared with control by the end of recovery (P < 0.05). Although exercise increased serum cortisol concentration threefold, there was no relation between differences in cortisol and exercise vs. control differences in normalized leptin. The increased leptin mass after exercise may have been related to greater plasma glucose concentration during recovery after exercise compared with the control condition.

Adult↗

Relation of leptin and insulin to adiposity-associated elevations in sympathetic activity with age in humans.

OBJECTIVE: To determine whether plasma leptin and insulin concentrations are related to adiposity-associated elevations in muscle sympathetic nerve activity (MSNA) with age in healthy adult humans. DESIGN: Cross-sectional investigation of young and older adult men. SUBJECTS: Thirty healthy adult men, 16 young (25+/-1 y, mean+/-s.e.) and 14 older (61+/-1 y). MEASUREMENTS/RESULTS: The older men had higher (P<0.05) levels of body mass, BMI, total fat mass and truncal fat mass (dual energy X-ray absorptiometry) than the young men. MSNA burst frequency (microneurography) was approximately 75% higher in the older men (P<0.001). Plasma leptin concentrations were approximately 150% higher (P<0.01), whereas plasma insulin concentrations were approximately 70% higher (P<0.05) in the older subjects. MSNA was related to both total (r=0.51, P<0.01) and truncal (r=0.56, P<0.01) fat mass. Plasma leptin concentrations were related to total and truncal fat mass (both r=0.83, P<0.001), and to MSNA (r=0.49, P<0.01). Plasma insulin concentrations were related to MSNA (r=0.38, P<0.05). We used partial correlation analyses to assess whether leptin and/or insulin are potential contributors to the relation between body fat and MSNA. Adjusting for the effects of plasma leptin, but not insulin, concentrations eliminated the significant relations between MSNA and total and truncal fat mass. CONCLUSION: Our results: (1) demonstrate a positive relation between MSNA and plasma leptin concentrations in young and older healthy men; and (2) support the concept that circulating leptin concentrations may act as a humoral signal contributing to adiposity-associated elevations in MSNA with age in adult humans.

Absorptiometry, Photon↗

Smaller differences in total and regional adiposity with age in women who regularly perform endurance exercise.

Our aim was to determine if women who regularly perform endurance exercise demonstrate age-related elevations in body mass and adiposity. Ninety-five healthy females were studied: premenopausal (n = 28; mean +/- SE age 30 +/- 1 yr) and postmenopausal (n = 31; 56 +/- 1 yr) endurance-trained runners and premenopausal (n = 17; 29 +/- 1 yr) and postmenopausal (n = 19; 61 +/- 1 yr) sedentary controls. In the runners, body mass did not differ across age, but percent fat and fat mass were higher (P < 0.05) in the postmenopausal women. The age-related difference in total body fat, however, was only approximately 50% as great (P < 0.01) as that observed in the sedentary controls due in part to smaller age-related differences in central (truncal) fat. The higher fat mass in the postmenopausal runners was modestly (inversely) related to both exercise volume (r = -0.44, P < 0.01) and maximal oxygen consumption (r = -0.41, P < 0.01). The present findings provide experimental support for the hypothesis that women who regularly engage in vigorous endurance exercise may not gain body weight, undergo only a modest increase in total body fat, and do not demonstrate a significant elevation in central adiposity with age.

Adipose Tissue↗

Role of central circulatory factors in the fat-free mass-maximal aerobic capacity relation across age.

Fat-free mass (FFM) (primarily skeletal muscle mass) is related to maximal aerobic capacity among healthy humans across the adult age range. The basis for this physiological association is assumed to be a direct relation between skeletal muscle mass and its capacity to consume oxygen. We tested the alternative hypothesis that FFM exerts its influence on maximal aerobic capacity in part via an association with central circulatory function. To do so, we analyzed data from 103 healthy sedentary adults aged 18-75 yr. FFM was strongly and positively related to maximal oxygen consumption (r = 0.80, P < 0. 001). FFM was also strongly and positively related to supine resting levels of blood volume (r = 0.79, P < 0.001) and stroke volume (r = 0.75, P < 0.001). Statistically controlling for the collective influences of blood volume and stroke volume abolished the tight relation between FFM and maximal oxygen consumption (r = 0.12, not significant). These results indicate that 1) FFM may be an important physiological determinant of blood volume and stroke volume among healthy sedentary adult humans of varying age; and 2) this relation between FFM and central circulatory function appears to represent the primary physiological basis for the strong association between FFM and maximal aerobic capacity in this population. Our findings suggest that sarcopenia (loss of skeletal muscle mass with aging) may contribute to the age-related decline in maximal aerobic capacity primarily via reductions in blood volume and stroke volume rather than a direct effect on the oxygen-consuming potential of muscle per se.

Adipose Tissue↗

Systemic hemodynamic determinants of blood pressure in women: age, physical activity, and hormone replacement.

We tested the hypothesis that the age-related changes in systemic hemodynamic determinants of arterial blood pressure in healthy women are related to physical activity and hormone replacement status. We studied 66 healthy, normotensive premenopausal (21-35 yr) and postmenopausal (50-72 yr) sedentary and endurance-trained women under supine resting conditions. Mean blood pressure was 7 mmHg higher in sedentary post- compared with premenopausal women, which was associated with an 11-mmHg higher systolic blood pressure, a 25% lower stroke volume and cardiac output, and a 50% higher systemic vascular resistance (all P < 0.05). Absolute (ml) levels of total blood volume did not differ across age, but resting oxygen consumption was approximately 35% lower in the postmenopausal women (P < 0.05). The elevations in mean and systolic blood pressures with age were similar in endurance-trained runners, but, in contrast to the sedentary women, the elevations were not associated with significant age-related differences in cardiac output, stroke volume, or oxygen consumption, and only a modest (15%) increase in systemic vascular resistance (P = 0.06). Postmenopausal swimmers demonstrated the same systemic hemodynamic profile as that of postmenopausal runners, indicating a nonspecific influence of the endurance-trained state. Blood pressure and its systemic hemodynamic determinants did not differ in postmenopausal users compared with those of nonusers of hormone replacement therapy. Resting oxygen consumption was the strongest physiological correlate of cardiac output in the overall population (r = 0.65, P < 0.001). We conclude that 1) the increases in arterial blood pressure at rest with age in healthy normotensive women are not obviously related to habitual physical activity status; 2) the systemic hemodynamic determinants of the age-related elevations in blood pressure are fundamentally different in sedentary vs. active women, possibly due, in part, to an absence of decline in resting oxygen consumption in the latter; and 3) systemic hemodynamics at rest are not different in healthy normotensive postmenopausal users vs. nonusers of estrogen-based hormone replacement.

Adult↗

Regular exercise and the age-related decline in resting metabolic rate in women.

A low resting metabolic rate (RMR) is a risk factor for future weight gain. We tested the hypothesis that the age-related decline in RMR in sedentary women is not observed in women who exercise regularly. Sixty-five healthy, weight-stable women, aged 21-35 or 50-72 yr, were studied: 12 premenopausal and 15 postmenopausal sedentary women, 13 premenopausal and 15 postmenopausal distance runners, and 10 endurance-trained postmenopausal swimmers. RMR was measured by indirect calorimetry (ventilated hood system) after an overnight fast, and values were adjusted for fat mass and fat-free mass (RMRadj). The RMRadj was approximately 10% lower in the postmenopausal vs. premenopausal sedentary women (52 +/- 2 vs. 57 +/- 2 Cal/h; P < 0.002). In contrast, RMRadj was not significantly different in the premenopausal (59 +/- 2 Cal/h) and postmenopausal (57 +/- 1 Cal/h) distance runners. The postmenopausal swimmers had a RMRadj (57 +/- 2 Cal/h) identical to that of the postmenopausal runners, suggesting a generalized influence of the endurance exercise-trained state in postmenopausal women. Group differences in RMRadj were not associated with differences in total energy intake or composition or with plasma concentrations of norepinephrine, T3, or T4. However, maximal oxygen consumption (aerobic fitness) accounted for 35% of the individual variance in RMRadj in the overall population (r = 0.59; P < 0.001). Our results are consistent with the concept that the age-related decline in RMR in sedentary women is not observed in women who regularly perform endurance exercise. The elevated level of RMR observed in middle-aged and older exercising women may play a role in their lower levels of body weight and fatness compared to those in sedentary women.

Adult↗