Insulin sensitivity in postmenopausal women: independent and combined associations with hormone replacement, cardiovascular fitness, and body composition

OBJECTIVE: The effects of combined physical activity and hormone replacement therapy (HRT) on insulin sensitivity in postmenopausal (PM) women are unclear. The purpose of the study was to test the following hypotheses: 1) PM women who have undergone vigorous exercise training have greater insulin sensitivity than PM women who are physically active and PM women who are sedentary, and 2) PM women using HRT have greater insulin sensitivity than PM women not using HRT. We also sought to determine whether body composition or cardiovascular fitness was the stronger predictor of insulin sensitivity in these women. RESEARCH DESIGN AND METHODS: Three groups of PM women classified as sedentary (n = 18), physically active (n = 19), and athletic (n = 23) underwent an insulin-modified frequently sampled intravenous glucose tolerance test to determine the insulin sensitivity index (SI) and dual-energy X-ray absorptiometry to determine body composition. RESULTS: There was a significant association between both physical activity (P = 0.036) and HRT (P = 0.007) and fasting plasma insulin levels. The athletic PM women had the lowest plasma insulin levels and the highest SI. Across all physical activity levels, PM women using HRT (n = 29) had significantly lower fasting plasma insulin levels and a lower SI than PM women not using HRT (n = 31). HRT was significantly (P = 0.025) associated with intravenous glucose tolerance (KG); the women not using HRT had a higher K(G); than the PM women using HRT (0.83 +/- 0.08 vs. 0.60 +/- 0.05% per minute). Percent body fat (r = -0.37, P = 0.004) and VO2max (r = 0.35, P = 0.007) were similar predictors of SI. CONCLUSIONS: We conclude that, although overall HRT was associated with an attenuated SI, vigorous exercise training was independently associated with the greatest SI. In addition, PM women using HRT may benefit from having lower plasma insulin levels, but they may also have a lower SI.     

Hormone replacement therapy, insulin sensitivity, and abdominal obesity in postmenopausal women.

OBJECTIVE: The purpose of this study was to determine whether insulin sensitivity differs between postmenopausal women taking estradiol, women on estrogen plus progesterone hormone replacement therapy (HRT), and women not on HRT and whether differences are explained by the differences in total and/or abdominal adiposity and fat deposition in the muscle. RESEARCH DESIGN AND METHODS: We studied 28 obese, sedentary postmenopausal Caucasian women. Women taking oral estrogen (n = 6) were matched for age (57 +/- 3 vs. 58 +/- 2 years), weight (87.9 +/- 6.0 vs. 83.0 +/- 3.9 kg), and BMI (33.9 +/- 1.7 vs. 33.9 +/- 1.9 kg/m(2)) with women not on HRT (n = 6). Eight women taking oral estrogen plus progesterone were matched with eight different women not on HRT for age (59 +/- 2 vs. 60 +/- 2 years), weight (82.8 +/- 3.7 vs. 83.7 +/- 4.1 kg), and BMI (30.7 +/- 1.0 vs. 29.9 +/- 1.3 kg/m(2)). RESULTS: VO(2max) (maximal aerobic capacity), percentage of fat, total body fat mass, and fat-free mass (FFM) were similar between groups. Visceral fat, subcutaneous abdominal fat, sagittal diameter, and mid-thigh low-density lean tissue (intramuscular fat) did not differ by hormone status. Basal carbohydrate and fat utilization was not different among groups. Fasting plasma glucose and insulin did not differ by hormone use. Glucose utilization (M) was measured during the last 30 min of a 3-h hyperinsulinemic-euglycemic clamp (40 mU. m(2). min(-1)). Postmenopausal women taking oral estrogen had a 31% lower M than women not on HRT (42.7 +/- 4.0 vs. 61.7 +/- 4.7 micromol. kg(FFM). min(-1), P < 0.05). M was 26% lower in women taking estrogen plus progesterone (44.0 +/- 3.5 vs. 59.7 +/- 6.2 micromol. kg(FFM). min(-1), P < 0.05) than women not on HRT. M/I, the amount of glucose metabolized per unit of plasma insulin (I), an index of insulin sensitivity, was 36% lower in women taking estrogen compared with matched women not on HRT (P < 0.05) and 28% lower in women taking estrogen plus progesterone compared with matched women not on HRT (P < 0.05). CONCLUSIONS: Postmenopausal women taking oral estrogen or those taking a combination of estrogen and HRT are more insulin-resistant than women not on HRT, even when women are of comparable total and abdominal adiposity.     

激素替代疗法和负重健走对绝经妇女骨密度及血脂的影响

目的探讨雌激素、负重健走运动及两者的联合对绝经妇女血脂、骨代谢和骨密度的影响。方法52名绝经妇女分成激素替代疗法组(n=12)、负重健走组(n=14)、激素替代疗法+负重健走组(n=12)和对照组(n=14)。激素替代疗法组服用复方尼尔雌醇片;负重健走组负5 kg重量,以60%～80%最大耗氧量进行健走运动;激素替代疗法+负重健走组同时接受前两组的干预。试验期为6个月,试验前后检测血脂、血碱性磷酸酶(ALP)、尿钙(Ca)和尿肌酐(Cr)的比值、L₂～L₄及左腿股骨头密度。结果试验结束后,3个试验组被试的血胆固醇(TC)、TC/高密度脂蛋白胆固醇(HDL-C)均低于试验前和对照组(P<0.05);负重健走组和激素替代疗法+负重健走组的HDL-C高于试验前水平和对照组(P<0.05);试验组血清ALP和空腹尿Ca/Cr均低于试验前(P<0.05)及对照组(P<0.01);3个试验组L₂～L₄及左腿股骨头骨密度均高于对照组(P<0.01)及试验前(P<0.05)。结论激素替代疗法和负重健走运动均能有效改善绝经后妇女的血脂组成,并有效预防和逆转妇女绝经引发的骨质疏松症。     

Effects of regular walking on cardiovascular risk factors and body composition in normoglycemic women and women with type 2 diabetes

OBJECTIVE: To examine the impact of a 12-week walking program on body composition and risk factors for cardiovascular disease in women with type 2 diabetes and in normoglycemic women with first-degree diabetic relatives. RESEARCH DESIGN AND METHODS: There were 11 postmenopausal women with type 2 diabetes and 20 normoglycemic women of similar age and BMI who were asked to walk 1 h per day on 5 days each week for 12 weeks. Fitness (estimated VO2max) was assessed with a 1.6-km walking test; body composition was measured by dual-energy X-ray absorptiometry; and sex hormone, metabolic, and lipid concentrations were measured in serum. RESULTS: After 12 weeks, estimated VO2max improved in both groups (P < 0.005). In the diabetic women, BMI and fat content of the upper body and android waist region decreased (P < 0.05). Concentrations of fasting blood glucose (P < 0.05) HbAlc (P < 0.05), total cholesterol (P < 0.005), and LDL cholesterol (P < 0.05) decreased, while HDL cholesterol and sex hormones were unchanged. In contrast, normoglycemic women failed to lose body fat after 12 weeks of exercise in a walking program. However, their HbAlc, total cholesterol, LDL cholesterol, sex hormone-binding globulin, and total testosterone concentrations decreased (P < 0.05). On pooling the data and including diabetes as a categorical grouping variable, stepwise multiple regression analysis indicated that the change in centralized body fat, but not the change in VO2max, was related to change in fasting blood glucose. CONCLUSIONS: Twelve weeks of walking increased the fitness of diabetic and normoglycemic women. Improvement of fasting blood glucose was related to the loss of centralized body fat rather than to improved fitness.     

Effect of long-term hormone replacement therapy on coronary endothelial function in postmenopausal women

OBJECTIVES: To determine the difference in endothelial function between premenopausal and postmenopausal women and to determine whether hormone replacement therapy (HRT) is associated with an improvement in coronary endothelial function. PATIENTS AND METHODS: Women undergoing coronary physiology studies for chest pain at the Mayo Clinic In Rochester, Minn, between December 1992 and April 2002 underwent assessment of coronary endothelium-independent and -dependent function with intracoronary administration of adenosine and acetylcholine, respectively. The coronary diameters, coronary blood flows, and coronary velocity reserves were measured. RESULTS: A total of 270 women (89 premenopausal and 181 postmenopausal) participated in the study. Endothelium-dependent coronary blood flow change (baseline to peak flow) in response to acetylcholine (10(-4), 10(-5), and 10(-4) mol/L) was lower in postmenopausal women compared with premenopausal women (39.7% vs 72.9%, P = .03). There was no significant difference between the postmenopausal women receiving and not receiving HRT with regard to percent change in coronary diameter (-21.8% vs -13.9%, P = .15), percent change in coronary blood flow (37.3% vs 42.7%, P = .74), or coronary velocity reserve (2.7 vs 2.7, P = .82). CONCLUSION: This study shows that the postmenopausal state is associated with a greater abnormality in coronary endothelial function at the level of the microcirculation. Moreover, HRT status was not associated with an improvement in coronary endothelial function in postmenopausal women.     

Markers of inflammation in women on different hormone replacement therapies

BACKGROUND AND AIM: To measure inflammatory markers in postmenopausal women on different forms of hormone replacement therapy (HRT). METHOD: C-reactive protein (CRP), fibrinogen, plasma viscosity (PV), albumin and white blood cell (WBC) count were determined in 749 postmenopausal women. RESULTS: CRP concentration was significantly higher in women on estrogen monotherapy (difference of the median (d) 0.96 mg/l, P = 0.013), compared to those without HRT, but there was no difference in women on combined HRT. Fibrinogen concentration was significantly lower in women on estrogen monotherapy (d 0.25g/l, P = 0.004) and combined HRT (d 0.4 g/l, P < 0.001), compared to women without HRT. Similarly, PV was significantly lower in women on estrogen monotherapy (d 0.017 mPa x s, P = 0.007) and women on combined HRT (d 0.039mPa x s, P < 0.001), compared to those without HRT. No differences were found for WBC count and the negative acute phase marker albumin in the various treatment groups. In contrast to oral estrogen administration, levels of CRP, fibrinogen and PV in women on transdermal estrogen therapy did not differ from the no-HRT group. There was no association between these markers of inflammation and plasma estrogen levels. CONCLUSION: Oral estrogen monotherapy was associated with highest concentrations of CRP. In contrast, other markers of inflammation were either similar or lower in the oral HRT group, compared to the group of women without HRT, suggesting that higher CRP concentrations reflect estrogen effects on CRP expression rather than a systemic pro-inflammatory effect.     

Markers of inflammation in women on different hormone replacement therapies

BACKGROUND AND AIM. To measure inflammatory markers in postmenopausal women on different forms of hormone replacement therapy (HRT). METHOD. C-reactive protein (CRP), fibrinogen, plasma viscosity (PV), albumin and white blood cell (WBC) count were determined in 749 postmenopausal women. RESULTS. CRP concentration was significantly higher in women on estrogen monotherapy (difference of the median (d) 0.96 &#114 mg/l, P &#114 = &#114 0.013), compared to those without HRT, but there was no difference in women on combined HRT. Fibrinogen concentration was significantly lower in women on estrogen monotherapy (d 0.25 &#114 g/l, P &#114 = &#114 0.004) and combined HRT (d 0.4 &#114 g/l, P &#114 < &#114 0.001), compared to women without HRT. Similarly, PV was significantly lower in women on estrogen monotherapy (d 0.017 &#114 mPa·s, P &#114 = &#114 0.007) and women on combined HRT (d 0.039 &#114 mPa·s, P &#114 < &#114 0.001), compared to those without HRT. No differences were found for WBC count and the negative acute phase marker albumin in the various treatment groups. In contrast to oral estrogen administration, levels of CRP, fibrinogen and PV in women on transdermal estrogen therapy did not differ from the no-HRT group. There was no association between these markers of inflammation and plasma estrogen levels. CONCLUSION. Oral estrogen monotherapy was associated with highest concentrations of CRP. In contrast, other markers of inflammation were either similar or lower in the oral HRT group, compared to the group of women without HRT, suggesting that higher CRP concentrations reflect estrogen effects on CRP expression rather than a systemic pro-inflammatory effect.     

Plasma adiponectin and leptin levels,body composition,and glucose utilization in adult women with wide ranges of age and obesity

OBJECTIVE: The purpose of this study was to determine the relationships between plasma adiponectin and leptin levels, total and central obesity, and glucose utilization across the adult age span. RESEARCH DESIGN AND METHODS: We studied 148 women aged 18-81 years with a BMI range of 17.2-44.3 kg/m(2). Total percent body fat was determined by dual-energy X-ray absorptiometry and abdominal fat by computed tomography. Glucose tolerance in non-type 2 diabetic volunteers was determined with an oral glucose tolerance test. Glucose utilization (M) was measured during the last 60 min of hyperinsulinemic-euglycemic clamps (240 pmol x m(-2) x min(-1)). Plasma adiponectin levels were measured by radioimmunoassay. The women were separated into three age-groups: young, middle, and old (<40, 40-59, and >or=60 years, respectively), as well as by glucose tolerance status. RESULTS: Adiponectin concentrations did not differ by age-groups. There were significant age effects for BMI, percent body fat, visceral fat, subcutaneous abdominal fat, VO(2max), and M. Adiponectin levels were lower in the prediabetic women (n = 18) than in the normal glucose-tolerant women (n = 108) and the women with type 2 diabetes (n = 22) (both P < 0.05). Univariate correlations revealed significant negative relationships between plasma adiponectin levels and BMI, percent body fat, visceral fat, subcutaneous abdominal fat, fasting leptin, and fasting insulin and positive relationship with M (all P < 0.05). In a multiple stepwise regression model to predict adiponectin, only M remained in the model at P < 0.001. Multivariate analyses revealed a significant relation for M as a function of adiponectin, insulin, and VO(2max). CONCLUSIONS: The data suggest that plasma adiponectin does not change with age but levels are negatively associated with percent body fat, visceral fat, subcutaneous abdominal fat, insulin, and leptin levels in women. Adiponectin is positively associated with M across the age span in women.     

The effect of hormone replacement therapy on oxidized low density lipoprotein levels and paraoxonase activity in postmenopausal women

Oxidized low-density lipoproteins (oxLDL) are involved in initiation of atherosclerosis. Paraoxonase 1 (PON1), the isoenzyme of PON, is located on high-density lipoprotein (HDL) and protects against the oxidative modification of both HDL and LDL by hydrolysing lipid peroxides. Postmenopausal women have a higher risk of cardiovascular events compared with premenopausal women. The aim of this clinical study was to evaluate the effects of hormone replacement therapy (HRT) on oxLDL and PON1 activity in menopausal status. The subjects included 45 healthy postmenopausal women, aged 43 to 57 years, and 30 premenopausal women with regular cycles, aged 31 to 40 years. None of the participating women had a history of hypertension, diabetes mellitus or medications known to affect the cardiovascular system. Twenty five of the postmenopausal women received conjugated estrogens at dose of 0.625 mg/day per oral (P.O.) and medroxyprogesterone acetate (MPA) (1 mg/d P.O.) for 10 days. Twenty of the postmenopausal women received 17-beta estradiol (2 mg/day) and norethysterone acetate (NETA) (5 mg/day P.O.) for 10 days. Fasting blood samples were taken from premenopausal women (baseline) and postmenopausal women after HRT of 6 months to determine serum malondialdehyde (MDA), oxLDL, and PON1 activity. After 6-month therapy, MDA and oxLDL levels showed a statistically significant reduction in the treated groups versus baseline (p <0.05), whereas PON1 activities were increased (p <0.05). Increase in oxidative status may be one of the factors leading to reduction in PON1 activity and increased oxLDL in menopause. HRT may be effective on oxidative stress and lipoprotein metabolism in apparently healthy postmenopausal women.     

The incidence of plateau at VO(2max) is affected by a bout of prior-priming exercise

The purpose of this study was to determine the effect of 6 min of prior-priming exercise on the incidence of plateau at VO(2max). Twelve trained cyclists (age, 21 ± 3 years; height, 175·0 ± 8·0 cm; weight, 69·0 ± 10·4 kg; maximal oxygen uptake (VO(2max)), 56·3 ± 6·9 ml kg(-1) min(-1)) completed three incremental tests to volitional exhaustion, which were classified as unprimed (UP), heavy-primed (HP) and severe-primed (SP), at a work rate of 1 W 2 s(-1), from an initial workload of 100 W, for the determination of VO(2max). VO(2max) trial in the HP and SP conditions was preceded by a period of 4-min unloaded cycling followed by a further 6 min of constant load cycling at Δ50% VO(2) gas exchange threshold (GET)-VO(2max) (HP) and Δ75% VO(2) GET-VO(2max) (SP). Expired air was recorded on a breath-by-breath basis during all trials. The criteria adopted for a plateau in VO(2max) was a ΔVO(2) over the final two consecutive 30-s sampling periods ≤ 2·1 ml kg(-1) min(-1). There was a significant increase in plateau responses between the UP (50%) and HP (100%) conditions (P = 0·001) coupled with a significant change in the slope of the regression line during the final 60 s of the VO(2max) test, UP and HP (P = 0·0299) and UP and SP (P = 0·0296). These data suggest that a bout of prior-priming exercise promotes an increased incidence of plateau responses at VO(2max) . It is suggested that future studies address how such an approach can be adopted without prior knowledge of GET.     

Six weeks of aerobic dance exercise improves blood oxidative stress status and increases interleukin-2 in previously sedentary women

This study evaluated the change in blood oxidative stress, blood interleukin-2, and physical performance following 6 weeks of moderate intensity and duration aerobic dance exercise in 24 sedentary women. Blood samples were collected at rest twice before (baseline) and after the 6-week intervention for analysis of protein hydroperoxide (PrOOH), malondialdehyde (MDA), total anti-oxidant capacity (TAC), and interleukin-2 (IL-2) levels. Maximal treadmill run time (Time(max)) and maximal oxygen consumption (VO(2max)) were also measured. All variables were statistically analyzed with a repeated measurement ANOVA and Tukey post hoc. No differences were noted in any variable during the baseline period (p > 0.05). After aerobic dance exercise, VO(2max), Time(max), TAC and IL-2 were significantly increased, whereas MDA levels were decreased significantly (p < 0.05). PrOOH did not change either between baseline measures or after exercise. It can be concluded that aerobic dance exercise at a moderate intensity and duration can improve physical fitness, decrease MDA, and increase TAC and IL-2 in previously sedentary women.     

Effects of postmenopausal hormone replacement therapy on HbA(1c) levels

OBJECTIVE: Estrogen seems to contribute to glucose homeostasis in women. The objective of this study was to examine the effects of hormone replacement therapy (HRT) on HbA(1c) levels in Japanese postmenopausal women and to determine whether the effects varied with age. RESEARCH DESIGN AND METHODS: We studied 99 postmenopausal women taking HRT (mean +/- SD age 56.5 +/- 6.9 years, BMI 21.5 +/- 2.3 kg/m(2)) and 101 postmenopausal women not on HRT (51.4 +/- 6.1 years, 21.3 +/- 2.4 kg/m(2)). HRT consisted of continuous conjugated equine estrogen (CEE; 0.625 mg/day) and medroxyprogesterone acetate (MPA; 2.5 mg/day) for >2 years. RESULTS: HbA(1c) levels are positively associated with age and BMI in women who use HRT as well as in those who do not use HRT. After adjusting for age and BMI, HRT showed no effects on HbA(1c) levels. However, HbA(1c) levels were significantly lower in postmenopausal women aged 40-49 years who were taking HRT than in women of similar age who were not taking HRT (mean +/- SE 4.776 +/- 0.092 vs. 5.096 +/- 0.078%, P < 0.05). No differences in HbA(1c) levels between women who did and did not use HRT were observed in those older than 50 years. CONCLUSIONS: Oral HRT involving CEE combined with MPA may decrease HbA(1c) levels in women aged 40-49 years and is likely to have no adverse effects on HbA(1c) levels in women older than 50 years.     

Sr and Fe relationship with hormone replacement therapy and bone mineral density

BACKGROUND: We determined blood strontium (Sr) and iron (Fe) concentrations and their relationship with bone mineral density (BMD) and some biochemical parameters in premenopausal and postmenopausal women without or with hormone replacement therapy (HRT). METHODS: Blood Sr and Fe concentrations, BMD, follicle stimulating hormone (FSH), 17beta-estradiol (E2), creatinine, albumin, blood calcium and alkaline phosphatase activity were determined in premenopausal and postmenopausal women without or with HRT (mean ages: 47, 59, and 57 y, respectively). RESULTS: Blood Sr (microg/l) and Fe (mg/l) concentrations in premenopausal (31.65+/-2.96 and 496.05+/-14.37) and postmenopausal women without (28.85+/-2.48 and 525.27+/-8.56) or with (25.98+/-2.73 and 535.77+/-17.57) HRT were not significantly different. BMD L1-L4 and BMD femur (g/cm2) were significantly higher in premenopausal women (1.05+/-0.02 and 0.84+/-0.02) when compared both to postmenopausal women without (0.90+/-0.03 and 0.75+/-0.02) and with (0.93+/-0.03 and 0.73+/-0.01) HRT. However, BMD had no relationship with blood metal concentrations. E2 concentrations were lower in postmenopausal women without HRT, while FSH concentrations were higher in both postmenopausal groups (p<0.05). CONCLUSIONS: Physiological whole blood Sr and Fe concentrations had no significant effect in BMD and other biochemical parameters in pre and postmenopausal women. However, BMD was negatively influenced by FSH concentrations and associated with age.     

Effects of exercise training on oxygen uptake kinetic responses in women with type 2 diabetes.

OBJECTIVE: Women with uncomplicated type 2 diabetes have both a decreased maximal oxygen consumption (VO2max) and slowed oxygen uptake (VO2) kinetics at the onset of exercise compared with nondiabetic women. These abnormalities are seen not only at maximal workloads, but also at the onset of low-level exercise. To evaluate the hypothesis that VO2max and VO2 kinetics would improve with exercise training in untrained people with type 2 diabetes, we measured these parameters in premenopausal sedentary women before and after 3 months of supervised exercise training. RESEARCH DESIGN AND METHODS: A total of 8 women with type 2 diabetes, 9 overweight nondiabetic women, and 10 lean nondiabetic women were studied. At baseline and after 3 months of exercise training, subjects underwent bicycle ergometer testing to obtain VO2max and VO2 kinetics data. RESULTS: On entry, women with type 2 diabetes had the lowest VO2max and slowest VO2 kinetics of the three groups. After exercise training, the women with type 2 diabetes improved their VO2max more than the lean and overweight control women: 28 vs. 5 and 8%, respectively (P < 0.05 for the diabetic group vs. both control groups). In the group with diabetes, VO2 kinetics improved by 39 and 22% at 20 and 30 W, respectively. For the control subjects, VO2 kinetics did not improve at any workload in either group. CONCLUSIONS: Despite beginning with the lowest VO2max and slowest VO2 kinetics, subjects with type 2 diabetes benefited more from an exercise training program than did control subjects. These findings suggest that in addition to its known metabolic effects, exercise training in individuals with type 2 diabetes may be an effective therapy to improve the cardiovascular response to exercise and to overcome low-level exercise impairment as reflected by improved VO2max and VO2 kinetics. If the ability to make circulatory adjustments at the beginning of exercise at low workloads is improved by an exercise training program, as suggested by the VO2 kinetics data, the clinical significance of exercise for people with type 2 diabetes is clear.     

Transdermal HRT and Doppler findings in normotensive and hypertensive postmenopausal patients.

OBJECTIVE: To evaluate the effects of transdermal hormone replacement therapy (HRT) on plasma viscosity, serum levels of thromboxane B2 (TXB2) and vascular impedance in the uterine, bladder wall, internal carotid and ophthalmic arteries in normotensive and hypertensive postmenopausal patients. METHODS: Thirty postmenopausal patients underwent continuous estradiol transdermal supplementation at a dose of 50 microg/day and 12-day courses of medroxyprogesterone acetate 10 mg/day every 2 months. The women were divided into two groups according to their blood pressure: normotensive women (Group 1, n=14) and hypertensive subjects (Group 2, n=16). Before starting HRT and after 6 months of therapy, the patients underwent: transvaginal ultrasonographic examination of the pelvic organs; Doppler examination of the blood flow velocities in the uterine, bladder wall, internal carotid and ophthalmic arteries; and analysis of plasma viscosity and plasma TXB2. RESULTS: After 6 months of HRT plasma viscosity had decreased in both groups (mean reduction in Group 1, (14+/-1)%, P=0.005; mean reduction in Group 2, (10+/-1)%, P=0.005) as had the TXB2 levels (mean reduction in Group 1, (93+/-2)%, P<0.001; mean reduction in Group 2, (92+/-3)%, P<0.001). The mean percentage reduction in plasma viscosity was smaller in hypertensive women than in normotensive women (P<0.05). There was also a significant reduction in vascular impedance in the uterine artery (mean reduction in Group 1, (16+/-1)%, P=0.005; mean reduction in Group 2, (19+/-1)%, P=0.005), the bladder wall arteries (mean reduction in Group 1, (23+/-2)%, P=0.005; mean reduction in Group 2, (18+/-1)%, P=0.005), the internal carotid artery (mean reduction in Group 1, (25+/-1)%, P=0.005; mean reduction in Group 2, (26+/-1)%, P=0.005) and the ophthalmic artery (mean reduction in Group 1, (24+/-2)%, P=0.005; mean reduction in Group 2, (16+/-1)%, P=0.005). The percentage reduction in vascular impedance did not differ significantly between the two groups. CONCLUSIONS: Our results show that transdermal HRT is effective in reducing plasma viscosity, TXB2 levels and vascular impedance in the peripheral and central vessels both in normotensive and hypertensive postmenopausal patients.     

运动训练对低肺功能肺癌患者手术耐受性的影响

目的:探讨术前短期中高强度下肢运动训练对低肺功能肺癌患者肺切除手术耐受性的影响.方法:采用随机单盲设计,将61例可切除肺癌合并重度慢性阻塞性肺病患者,根据美国胸科医师协会肺切除术前评估指南分为可手术A组和不可手术B组;A组再随机分为A1亚组(训练亚组)和A2亚组(对照组).A1亚组和B组术前予每周5次、连续2周、强度达60％-80％峰值氧摄量VO2max的踏车运动训练,辅以胸腹联合缩唇呼吸训练.比较训练前后静态肺功能和运动心肺功能的变化;训练后重新评估B组手术风险;比较训练Al亚组和对照A2组肺切除术后并发症情况.结果:训练后,在A1亚组,心肺功能指标:肺一氧化碳弥散量DLCO(P=0.003)、VO2max(P＜0.001)、无氧阈AT(P=0.008)、氧脉VO2max/HR(P＜0.001)较训练前显著改善;在B组,心肺功能指标:用力肺活量FVC(P＜0.001)、分钟最大通气量MVV (P=0.001)、DL.CO (P＜0.001)、最大功率W(P=0.004)、VO2max (P＜0.001)、AT(P=0.002)、VO2max/HR (P=0.00l)、峰值通气量VEmax(P=0.015)、无氧阈时CO2通气当量VE/VCO2@AT (P=0.003)和运动后经皮血氧饱和度SPO2％(P=0.002)均较训练前显著改善;B组中59％(10/17)患者达手术标准;训练A1亚组较对照A2组,肺切除术后氧疗时间(P=0.04)、机械通气时间(P=0.036)和住院天数(P=0.025)均显著缩短.结论:术前短期中高强度下肢运动训练能有效、可行地提高低肺功能肺癌患者心肺功能适应性,有助于肺切除术后康复.     

Physical fitness effect on bone mass in postmenopausal women

This study was conducted to determine if bone mineral mass is influenced by the level of physical fitness in active, healthy, postmenopausal women from 50 through 59 years of age. In vivo neutron activation analysis (NAA) was used to measure calcium or bone mineral in the trunk and proximal femurs. The NAA measurement is expressed as calcium bone index (CaBI), which relates the subject's Ca value to the estimated mean value for normal subjects of the same size based on height and arm span. The normal CaBI is 1.00 +/- 0.12 (ISD). The level of physical fitness was determined by calculating the maximum oxygen uptake (VO2max), attained by a graded exercise test on the treadmill, and evaluating the muscle strength in performing one repetition maximum in the bench press and leg press. The "above-average fit" group (VO2max greater than 29 ml/kg/min) when compared to the "average fit" group (VO2max 21-29 ml/kg/min) had significantly higher CaBI (p less than 0.001) and leg press (p less than 0.01). There was significant correlation between VO2max and CaBI (p less than 0.01). The findings suggest that level of physical activity may modify the amount of bone loss in postmenopausal women.     

Mechanism of enhanced insulin sensitivity in athletes. Increased blood flow, muscle glucose transport protein (GLUT-4) concentration, and glycogen synthase activity.

We examined the mechanisms of enhanced insulin sensitivity in 9 male healthy athletes (age, 25 +/- 1 yr; maximal aerobic power [VO2max], 57.6 +/- 1.0 ml/kg per min) as compared with 10 sedentary control subjects (age, 28 +/- 2 yr; VO2max, 44.1 +/- 2.3 ml/kg per min). In the athletes, whole body glucose disposal (240-min insulin clamp) was 32% (P < 0.01) and nonoxidative glucose disposal (indirect calorimetry) was 62% higher (P < 0.01) than in the controls. Muscle glycogen content increased by 39% in the athletes (P < 0.05) but did not change in the controls during insulin clamp. VO2max correlated with whole body (r = 0.60, P < 0.01) and nonoxidative glucose disposal (r = 0.64, P < 0.001). In the athletes forearm blood flow was 64% greater (P < 0.05) than in the controls, whereas their muscle capillary density was normal. Basal blood flow was related to VO2max (r = 0.63, P < 0.05) and glucose disposal during insulin infusion (r = 0.65, P < 0.05). The forearm glucose uptake in the athletes was increased by 3.3-fold (P < 0.01) in the basal state and by 73% (P < 0.05) during insulin infusion. Muscle glucose transport protein (GLUT-4) concentration was 93% greater in the athletes than controls (P < 0.01) and it was related to VO2max (r = 0.61, P < 0.01) and to whole body glucose disposal (r = 0.60, P < 0.01). Muscle glycogen synthase activity was 33% greater in the athletes than in the controls (P < 0.05), and the basal glycogen synthase fractional activity was closely related to blood flow (r = 0.88, P < 0.001). In conclusion: (a) athletes are characterized by enhanced muscle blood flow and glucose uptake. (b) The cellular mechanisms of glucose uptake are increased GLUT-4 protein content, glycogen synthase activity, and glucose storage as glycogen. (c) A close correlation between glycogen synthase fractional activity and blood flow suggests that they are causally related in promoting glucose disposal.     

Rosiglitazone improves exercise capacity in individuals with type 2 diabetes

OBJECTIVE: Although exercise is recommended as a cornerstone of treatment for type 2 diabetes, it is often poorly adopted by patients. We have noted that even in the absence of apparent cardiovascular disease, persons with type 2 diabetes have an impaired ability to carry out maximal exercise, and the impairment is correlated with insulin resistance and endothelial dysfunction. We hypothesized that administration of a thiazolidinedione (TZD) agent would improve exercise capacity in type 2 diabetes. RESEARCH DESIGN AND METHODS: Twenty participants with uncomplicated type 2 diabetes were randomly assigned in a double-blind study to receive either 4 mg/day of rosiglitazone or matching placebo after baseline measurements to assess endothelial function (brachial artery diameter by brachial ultrasound), maximal oxygen consumption (VO(2max)), oxygen uptake (VO(2)) kinetics, and insulin sensitivity by hyperinsulinemic-euglycemic clamp. Measurements were reassessed after 4 months of treatment. RESULTS: Participant groups did not differ at baseline in any measure. Rosiglitazone-treated participants (n = 10) had significantly improved VO(2max) (19.8 +/- 5.3 ml . kg(-1) . min(-1) before rosiglitazone vs. 21.2 +/- 5.1 ml . kg(-1) . min(-1) after rosiglitazone, P < 0.01), insulin sensitivity, and endothelial function. A change in VO(2max) correlated with improved insulin sensitivity measured by clamp (r = 0.68, P < 0.05) and with improved brachial artery diameter (r = 0.70, P < 0.05). Placebo-treated participants (n = 10) showed no changes in VO(2max) (19.4 +/- 5.2 ml . kg(-1) . min(-1) before rosiglitazone vs. 18.1 +/- 5.3 ml . kg(-1) . min(-1) after rosiglitazone, NS) or brachial artery diameter. CONCLUSIONS: This is the first known report showing that a TZD improved exercise function in type 2 diabetes. Whether this is due to the observed improvements in insulin sensitivity and/or endothelial function or to another action of the TZD class requires further exploration.     

Effects of hormone replacement therapy on blood platelets

BACKGROUND: Hormone replacement therapy (HRT) increases the risk of cardiovascular morbidity in postmenopausal women under certain circumstances. Part of this effect may be the result of the influence of HRT on blood platelets. We studied the effect of short-term oral hormone replacement therapy (unopposed oestradiol or sequentially combined oestradiol and trimegestone or dydrogesterone) on platelet activation parameters in healthy postmenopausal women. DESIGN: We designed a prospective, randomised, placebo-controlled 12-week study. Sixty healthy, normotensive, nonhysterectomised, postmenopausal women received daily micronised oestradiol (E2) 2 mg (n = 16), or 2 mg E2 daily sequentially combined with either trimegestone 0.5 mg daily (n = 14) or dydrogesterone 10 mg daily (n = 14), or placebo (n = 16). Data on platelet activation were collected at baseline and after 12 weeks of treatment using flow cytometry. RESULTS: Twelve weeks of treatment with combined HRT was associated with an increase in platelet activation parameters P-selectin and glycoprotein 53 (by 17% and 14%, respectively, P = 0.04 vs. the placebo group for both comparisons), suggesting alpha granule and lysosome degranulation. E2 replacement therapy was associated with an increase in P-selectin labelling by 22% (P = 0.04 vs. the placebo group). CONCLUSION: Short-term treatment with oestradiol or combined HRT increases the amount of circulating activated platelets as measured by flow cytometry. This could be a mechanism by which short-term HRT might increase the risk of thrombosis.