Exercise training, genetics and type 2 diabetes-related phenotypes.

Type 2 diabetes mellitus (T2DM) is at virtually pandemic levels world-wide. Diabetes has been referred to as 'a geneticist's nightmare'. However, dramatic advances in our understanding of the genetics of T2DM have occurred in the past 5 years. While endurance exercise training and increased habitual physical activity levels have consistently been shown to improve or be associated with improved T2DM-related phenotypes, there is substantial interindividual variation in these responses. There is some evidence that T2DM-related phenotype responses to exercise training are heritable, indicating that they might have a genetic basis. Genome-wide linkage studies have not identified specific chromosomal loci that could account for these differences, and no genome-wide association studies have been performed relative to T2DM-related phenotype responses to exercise training. From candidate gene studies, there are relatively strong and replicated data supporting a role for the PPARγ Pro12Ala variant in the interindividual differences in T2DM-related phenotype responses to training. This is a potentially important candidate locus because it affects T2DM susceptibility, has high biological plausibility and is the target for the primary pharmaceutical method for treating T2DM. Is it time to conduct a hypothesis-driven large-scale exercise training intervention trial based on PPARγ Pro12Ala genotype with T2DM-related phenotypes as the primary outcome measures, while also assessing potential mechanistic changes in skeletal muscle and adipose tissue? Or would it be more appropriate to propose a smaller trial to address the specific skeletal muscle and adipose tissue mechanisms affected by the interaction between the PPARγ Pro12Ala genotype and exercise training?

Nitro-oxidative stress biomarkers in active and inactive men.

Oxidative stress markers are novel factors shown to be related to cardiovascular (CVD) risk. We examined the effects of long-term exercise, age, and their interaction on plasma oxidized LDL (ox-LDL), nitrotyrosine, and myeloperoxidase (MPO) levels, all biomarkers of oxidative stress, and determined their association with plasma nitric oxide (NOx) levels as an index of NO bioavailability. Older (62±2 yr) active men (n=12) who had exercised for >30 years and young (25±4 yr) active men (n=7) who had exercised for >3 years were age- and BMI-matched to older (n=11) and young (n=8) inactive men. Young subjects had lower plasma nitrotyrosine levels than older subjects (P=0.047). Young inactive subjects had higher ox-LDL levels than either the young active (P=0.042) or the older active (P=0.041) subjects. In addition, plasma oxidative stress levels, particularly ox-LDL, were correlated with various conventional plasma lipoprotein-lipid levels, and in older subjects were associated with Framingham risk score (r=0.49, P=0.015). We found no relationships between plasma oxidative stress markers and NOx levels. The findings suggest that a sedentary lifestyle may be associated with higher ox-LDL levels and that the levels of oxidative stress markers are related to levels of other conventional CVD risk factors and overall CVD risk.

Effects of endurance exercise training on markers of cholesterol absorption and synthesis.

Abnormal cholesterol metabolism, including low intestinal cholesterol absorption and elevated synthesis, is prevalent in diabetes, obesity, hyperlipidemia, and the metabolic syndrome. Diet-induced weight loss improves cholesterol absorption in these populations, but it is not known if endurance exercise training also improves cholesterol homeostasis. To examine this, we measured circulating levels of campesterol, sitosterol, and lathosterol in 65 sedentary subjects (average age 59 years; with at least one metabolic syndrome risk factor) before and after 6 months of endurance exercise training. Campesterol and sitosterol are plant sterols that correlate with intestinal cholesterol absorption, while lathosterol is a marker of whole body cholesterol synthesis. Following the intervention, plant sterol levels were increased by 10% (p<0.05), but there was no change in plasma lathosterol. In addition, total and LDL-cholesterol were reduced by 0.16 mmol and 0.10 mmol, respectively (p<0.05), while HDL-C levels increased by 0.09 mmol (p<0.05). Furthermore, the change in plant sterols was positively correlated with the change in VO2max (r=0.310, p=0.004), independent of other metabolic syndrome risk factors. These data indicate that exercise training reduces plasma cholesterol despite increasing cholesterol absorption in subjects with metabolic syndrome risk factors.

Genetic markers of fibrinolytic responses of older persons to exercise training.

We assessed the interactive effect of genetic polymorphisms and exercise training on fibrinolysis in 50 - 75 yr old men (n = 17) and women (n = 28). Subjects had tissue plasminogen activator (t-PA) antigen levels and activity and plasminogen activator inhibitor-1 (PAI-1) activity measured before and after 6 mo of endurance-exercise training. Subject's DNA was typed for the PAI-1 4 G/5 G and t-PA I/D variants. Baseline PAI-1 activity, t-PA activity, and t-PA antigen levels were not different among PAI-1 or t-PA genotype groups. Overall, exercise training did not change PAI-1 activity (- 0.43 +/- 0.81 IU/mL, p = NS), increased t-PA activity (0.37 +/- 0.16 IU/mL, p = 0.02), and decreased t-PA antigen levels (- 0.88 +/- 0.20 ng/mL, p < 0.001). Although the differences in changes with training were not significant among genotype groups, significant t-PA antigen level improvements were evident only in PAI-1 4 G allele carriers and significant t-PA activity increases only in PAI-1 4 G homozygotes. t-PA genotype affected the training-induced t-PA antigen level improvements (p = 0.033) after covarying for gender and baseline t-PA antigen levels, with the smallest and largest reductions in the D homozygotes and I/D heterozygotes, respectively. These findings could have important treatment implications for the use of exercise training to reduce CV disease and thrombotic risk in older men and women.

NOS3 gene polymorphisms and exercise hemodynamics in postmenopausal women.

We tested whether the G894T and T-786C NOS3 polymorphisms were associated with exercise cardiovascular (CV) hemodynamics in sedentary, physically active, and endurance-trained postmenopausal women. CV hemodynamic parameters including heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressures and cardiac output (Q), as determined by acetylene rebreathing, stroke volume (SV), arteriovenous oxygen difference (a-vO2 diff), and total peripheral resistance (TPR) were measured during submaximal (40, 60, 80 %) and maximal (approximately 100 % VO2max) exercise. NOS3 G894T genotype was not significantly associated, either independently or interactively with habitual physical activity (PA) level, with SBP, Q, TPR, or a-vO2 diff during submaximal or maximal exercise. However, NOS3 894T non-carriers had a higher submaximal exercise HR than NOS3 894T allele carriers (120 +/- 2 vs. 112 +/- 2 beats/min, p = 0.007). NOS3 894T allele carriers had a higher SV than 894T non-carriers (78 +/- 2 vs. 72 +/- 2 ml/beat, p = 0.03) during submaximal exercise. NOS3 894T non-carriers also had a higher maximal exercise HR averaged across habitual PA groups than T allele carrier women (165 +/- 2 vs. 158 +/- 2 beats/min, p = 0.04). NOS3 894T allele carriers also tended to have a higher SV during maximal exercise than 894T non-carriers (70 +/- 2 vs. 64 +/- 2 ml/beat, p = 0.08). NOS3 T-786C genotype was not significantly associated, either independently or interactively, with any of the CV hemodynamic measures during submaximal or maximal exercise. These results suggest an association of NOS3 G894T genotype with submaximal and maximal exercise CV hemodynamic responses, especially HR, in postmenopausal women.

No association between ACE I/D polymorphism and cardiovascular hemodynamics during exercise in young women.

The ACE I/D polymorphism has been shown to interact with habitual physical activity levels in postmenopausal women to associate with submaximal and with maximal exercise hemodynamics. This investigation was designed to assess the potential relationships between ACE genotype and oxygen consumption (VO2), cardiac output (Q), stroke volume (SV), heart rate (HR), blood pressure (BP), total peripheral resistance (TPR), and arteriovenous oxygen difference ([a-v]O2 diff) during submaximal and maximal exercise in young sedentary and endurance-trained women. Seventy-seven 18-35-yr-old women underwent a maximal exercise test and a number of cardiac output tests on a treadmill using the acetylene rebreathing technique. ACE genotype was not significantly associated with VO2max (II 41.4+/-1.2, ID 39.8+/-0.9, DD 39.8+/-1.1 ml/kg/min, p=ns) or maximal HR (II 191+/-2, ID 191+/-1, DD 193+/-2 bpm, p=ns). In addition, systolic and diastolic BP, (a-v)O2 diff, TPR, SV, and Q during maximal exercise were not significantly associated with ACE genotype. During submaximal exercise, SBP, Q, SV, HR, TPR, and (a-v)O2 diff were not significantly associated with ACE genotype. However, the association between diastolic BP during submaximal exercise and ACE genotype approached significance (p=0.08). In addition, there were no statistically significant interactions between ACE genotype and habitual physical activity (PA) levels for any of the submaximal or the maximal exercise hemodynamic variables. We conclude that the ACE I/D polymorphism was not associated, independently or interacting with habitual PA levels, submaximal, or maximal cardiovascular hemodynamics in young women.

Physical activity, hormone replacement therapy and plasma lipoprotein-lipid levels in postmenopausal women.

We assessed the cross-sectional associations between hormone replacement therapy (HRT), habitual physical activity levels and plasma lipoprotein-lipid levels in postmenopausal women. Sedentary (n = 19), active nonathlete (n = 20) and endurance-trained (n = 21) postmenopausal women, with half of each group on and half not on HRT, underwent assessments of plasma lipids, VO2max, body composition, diet and common genetic variants. The groups' physical characteristics were generally similar though body weight was higher in the active nonathletes, and body fat was lower and VO2max higher in the athletes. HRT was associated with beneficial total cholesterol, LDL-C and HDL-C levels in sedentary and active nonathlete women. Plasma lipoprotein-lipid profiles were similar in women athletes on and not on HRT, with their profiles being only slightly better than sedentary and physically-active women on HRT. After controlling for HRT status, VO2max was correlated with total cholesterol (r = -0.51, p = 0.0001), LDL-C (r = -0.52, p = 0.0001), HDL-C (r = 0.25, p = 0.055), HDL 2 -C (r = 0.24, p = 0.08) and TG levels (r = -0.46, p = 0.0001). After controlling for HRT status, % body fat was correlated with total cholesterol (r = 0.43, p = 0.001), LDL-C (r = 0.38, p = 0.003), HDL-C (r = -0.29, p = 0.025), HDL 2 -C (r = -0,26, p = 0.07) and TG levels (r = 0.40, p = 0.002). Dietary fat intake was similar among the groups. APO E genotype was only associated with plasma lipid profiles in athletes, as those with at least one APO E2 allele tended to have better lipid profiles than those with only APO E3 or E4 alleles. Thus, HRT, exercise training and body composition are associated with plasma lipid levels in postmenopausal women; common polymorphic variations at key lipid metabolism-related gene loci also may interact with exercise training to affect their plasma lipid profiles.

Obesity gene variant and elite endurance performance.

beta2-adrenergic receptor (ADRB2) Gln27Glu genotype was determined in sedentary (n = 19), active (n = 20), and elite endurance athletic (n = 24) Caucasian postmenopausal women. Age was similar in all physical activity and ADRB2 genotype groups. ADRB2 genotypes were in Hardy-Weinberg equilibrium in sedentary and active women, but not in the athletes (chi(2) = 4.28, P <.05), due to the near absence of ADRB2 Glu27Glu homozygotes among the athletes. Weight tended to be higher in ADRB2 Glu27Glu women (63.5 +/- 1.8 v 57.7 +/- 1.7 and 60.0 +/- 1.8, P =.08), as did body mass index (BMI) (25.0 +/- 0.4 v 22.9 +/- 0.6 and 23.4 +/- 0.5 kg/m(2), P =.05), due to a higher fat mass in Glu27Glu women (24.1 +/- 1.0 v 18.1 +/- 1.4 and 20.1 +/- 1.4 kg, P <.05). Maximal O2 consumption was lower in ADRB2 Glu27Glu than in ADRB2 Glu27Gln and Gln27Gln genotype women (25.4 +/- 1.1 v 32.4 +/- 1.5 and 29.1 +/- 1.7 mL/kg/min, P <.05). We conclude that the Glu27Glu ADRB2 genotype may dissociate from and the Gln27Gln and Gln27Glu genotypes may associate with elite endurance performance in older women.

FABP2 genotype is associated with insulin sensitivity in older women.

This study determined whether sequence variations in genes related to glucose and insulin metabolism are associated with insulin sensitivity in postmenopausal women after accounting for habitual physical activity levels, body composition, and hormone-replacement therapy (HRT). Eighteen sedentary, 19 physically active, and 23 athletic postmenopausal white women underwent a frequently sampled intravenous glucose tolerance test to determine insulin sensitivity (S(I)) and dual-energy x-ray absorptiometry to determine body composition. After accounting for the effects of body composition, habitual physical activity levels, and HRT status, S(I) was 26% lower in subjects with the Thr54 fatty acid-binding protein 2 (FABP2) allele compared with Ala54 homozygotes (4.3 +/- 0.5 v 5.8 +/- 0.6 microU x 10(-4)/min/mL; P <.05). Angiotensin-converting enzyme genotype was not significantly associated with S(I). There were no significant associations between Gln27Glu beta(2)-adrenergic receptor or Pro12Ala peroxisome proliferator-activated receptor gamma variants and glucose or insulin kinetic parameters. It was concluded that FABP2 genotype influences insulin sensitivity independent of body composition, habitual physical activity levels, and HRT status in postmenopausal white women.

Acute resistive exercise does not affect ambulatory blood pressure in young men and women.

PURPOSE: Resistive exercise elicits a pressor response that results in a dramatic increase in blood pressure (BP) during the exercise. However, it is not known if the BP elevation persists after resistive exercise. METHODS: This study examined the effects of an acute resistive exercise session on 24-h ambulatory BP in sedentary (5 men, 6 women), resistance-trained (6 men, 6 women), and endurance-trained (4 men, 6 women) young subjects (age 22 +/- 3.2 yr) with normal BP. Two 24-h ambulatory BP recordings were made on each subject, one after two sets of resistive exercise on 12 weight machines and one after 48 h without prior exercise. RESULTS: Systolic, diastolic, and mean arterial BP and heart rate (HR) were not different in the hours after and for up to 24 h after the single resistive exercise session compared with the control day. There also was no difference in the ambulatory BP or HR response after the single session of resistive exercise based on the training status of the subjects. CONCLUSION: Thus, the elevated BP that occurs during resistive exercise does not persist in the 24 h after acute resistive exercise in sedentary, resistance-trained, or endurance-trained, young, normotensive men and women.

Specific genetic markers of endurance performance and VO2max.

Specific genetic markers of endurance performance and VO2max. Exerc. Sport Sci. Rev., Vol. 29, No. 1, pp 15-19, 2001. Recent advances have revolutionized genetic studies of quantitative traits. Mitochondrial DNA and creatine kinase variations may influence VO2max. Other data strongly suggest that angiotensin-converting enzyme genotype affects VO2max and endurance performance capacity, but the mechanisms are unclear. A recent genome-wide scan study also has provided candidate loci requiring further study.

Moderate physical activity is associated with higher bone mineral density in postmenopausal women.

OBJECTIVES: To determine the associations between different levels of habitual physical activity, hormone replacement therapy (HRT), and bone mineral density (BMD) in postmenopausal women. DESIGN: Cross-sectional. SETTING: Academic medical center. PARTICIPANTS: Twenty sedentary women, 20 active nonathletic women, and 23 endurance-trained athletes, all of whom were postmenopausal, with half of each group on and half not on HRT. MEASUREMENTS: BMD and body composition determined by dual energy x-ray absorptiometry, maximal oxygen consumption (VO2max), dietary history by questionnaire, and vitamin D receptor (VDR) genotyping on deoxyribonucleic acid. RESULTS: Body weight was higher in the active nonathletic than in the sedentary and athletic women. Body fat was lower and VO2max higher in the athletic women than in the sedentary and the active nonathletic women. Physical activity level was significantly associated with BMD in three of the five measurements taken (L1-L4 lumbar spine, trochanter, total body; all P < .05). These differences were also generally significant after adjusting for body weight. The association between physical activity status and BMD at the neck of the femur and Ward's triangle bordered on significance (P = .07-.09). At most sites, the active nonathletic women had higher BMD than did the sedentary and athletic women. HRT was significantly associated only with total body BMD (P < .05). The groups were similar in terms of dietary habits (protein, calcium, sodium, phosphorus intake); VDR genotypes; and family, smoking, and nutritional histories. CONCLUSION: Given the similarity of the groups with respect to other factors that affect BMD, it appears that prolonged low-to-moderate-intensity physical activity, but not the same number of years of higher-intensity training for competitive events, was independently associated with higher BMD.

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.

APO E gene and gene-environment effects on plasma lipoprotein-lipid levels.

Apolipoprotein E (apo E) is important in plasma lipid metabolism and is a component of several plasma lipoprotein-lipid particles. Three major apo E isoforms are encoded by three common alleles at the APO E locus. The E2 allele is associated with lower and the E4 allele with higher total plasma cholesterol and LDL cholesterol levels compared with the E3 allele. Available data generally indicate that APO E2, and possibly E3, genotype individuals reduce plasma total and low-density lipoprotein (LDL) cholesterol levels more than APO E4 individuals with statin therapy. Some evidence also indicates that APO E2 individuals are more likely to respond favorably to gemfibrozil and cholestyramine. On the other hand, it appears that with probucol, APO E4 genotype individuals may improve plasma lipoprotein-lipid profiles more than APO E3 individuals. APO E2 and E3 genotype perimenopausal women appear to improve plasma lipoprotein-lipid profiles more with hormone replacement therapy than APO E4 women. On the other hand, low-fat diet interventions tend to reduce plasma LDL cholesterol and, perhaps, plasma total cholesterol levels more in APO E4 than in APO E2 or E3 individuals. Both cross-sectional and longitudinal studies generally indicate that APO E2 and E3 individuals improve plasma lipoprotein-lipid profiles more with exercise training than APO E4 individuals. Although these data are hardly definitive, they lend strong support for the possibility that in the near future individuals will be directed to what might be their optimal therapy for improving plasma lipoprotein-lipid profiles and cardiovascular disease risk based partially on APO E genotype.

Determinants of body composition in postmenopausal women.

BACKGROUND: Little is known about the effects of different levels of long-term physical activity on total body and regional fat and whether hormone replacement therapy interacts with physical activity level to affect body composition in postmenopausal women. METHODS: We determined the associations between different levels of habitual physical activity, hormone replacement therapy (HRT), and total and regional body composition in postmenopausal women. Twenty sedentary, 20 active nonathletic, and 23 endurance-trained women (approximately half on HRT) had total and regional body composition assessed by dual-energy x-ray absorptiometry. The athletes and active nonathletic women had been active for the same number of years and the same number of hours per week. RESULTS: The athletes and sedentary women weighed the same, but the active nonathletic groups on and not on HRT weighed 3-12 kg more (p < .05). Athletes had less trunk, arm, leg, and total body fat than sedentary and active nonathletic women (p < .05). Women on HRT tended to have lower total body (p = .07), but not regional, fat values. Linear regression analyses indicated that VO2max in ml/kg/min was the major independent determinant of total and regional body fat accounting for 52% to 70% of their variances. Athletes had greater caloric and carbohydrate intake than their less active peers, but all groups had similar protein, fat, saturated fat, monounsaturated fat, and polyunsaturated fat intakes. CONCLUSIONS: Intense training, but not low- to moderate-intensity physical activity, is associated with markedly lower levels of total and regional body fat in postmenopausal women. HRT has less of an effect on body composition than intense exercise training in postmenopausal women.

The role of exercise training in the treatment of hypertension: an update.

Hypertension is a very prevalent cardiovascular (CV) disease risk factor in developed countries. All current treatment guidelines emphasise the role of nonpharmacological interventions, including physical activity, in the treatment of hypertension. Since our most recent review of the effects of exercise training on patients with hypertension, 15 studies have been published in the English literature. These results continue to indicate that exercise training decreases blood pressure (BP) in approximately 75% of individuals with hypertension, with systolic and diastolic BP reductions averaging approximately 11 and 8mm Hg, respectively. Women may reduce BP more with exercise training than men, and middle-aged people with hypertension may obtain greater benefits than young or older people. Low to moderate intensity training appears to be as, if not more, beneficial as higher intensity training for reducing BP in individuals with hypertension. BP reductions are rapidly evident although, at least for systolic BP, there is a tendency for greater reductions with more prolonged training. However, sustained BP reductions are evident during the 24 hours following a single bout of exercise in patients with hypertension. Asian and Pacific Island patients with hypertension reduce BP, especially systolic BP, more and more consistently than Caucasian patients. The minimal data also indicate that African-American patients reduce BP with exercise training. Some evidence indicates that common genetic variations may identify individuals with hypertension likely to reduce BP with exercise training. Patients with hypertension also improve plasma lipoprotein-lipid profiles and improve insulin sensitivity to the same degree as normotensive individuals with exercise training. Some evidence also indicates that exercise training in hypertensive patients may result in regression of pathological left ventricular hypertrophy. These results continue to support the recommendation that exercise training is an important initial or adjunctive step that is highly efficacious in the treatment of individuals with mild to moderate elevations in BP.

Aerobic exercise training-induced reductions in abdominal fat and glucose-stimulated insulin responses in middle-aged and older men.

OBJECTIVE: To test the effects of aerobic exercise training on glucose-stimulated insulin responses in middle-aged and older individuals. DESIGN: A 9-month moderate-intensity aerobic exercise training trial in 17 men. SETTING: An academic medical center. INTERVENTION: Subjects walked, jogged, or cycled at 50 to 60% heart rate reserve (HRR) three times per week for 30 to 45 minutes and progressed over 6 to 9 months until subjects were training at 80 to 85% of HRR for 45 to 60 minutes three to four times per week. Training intensity was stabilized for 2 weeks before retesting. Diets were stabilized on American Heart Association Step I diets before training, and calories increased to prevent weight loss. MEASUREMENTS: At baseline and after training, subjects underwent measurement of body fat (hydrodensitometry), regional fat distribution (waist-to-hip ratio (WHR)), VO2 max (maximal treadmill testing), diet intake (7-day food records), and glucose and insulin responses during 75 g, 2-hour oral glucose tolerance tests (OGTT) and 2-hour hyperglycemic (+/-7.9 mmol/L) glucose clamps. RESULTS: Aerobic exercise training increased VO2 max by 15% and decreased body fat from 22.8 +/- 1.6 to 20.8 +/- 1.5% (P < .0001), waist circumference by 2% (P = .038), and WHR by 1% (P = .035). Fasting glucose and insulin levels, and glucose responses during the OGTT did not change, but insulin responses during the OGTT decreased 16% (P = .027) after training. Training reduced early (0-10 minutes) and late (20-120 minutes) phase insulin responses by 14% (P = .017 and .042, respectively), but did not significantly change glucose disposal (+8%, P = .398). Multiple regression analyses showed that changes in waist circumference (r2 = 0.68, P < .0001) and percent body fat (r2 = 0.08, P = .049) were independent predictors of the reductions in the late phase insulin responses with exercise training, however, changes in VO2 max were not (P = .199). CONCLUSIONS: The decrease in glucose-stimulated insulin secretion with aerobic exercise training in middle-aged and older men appears to be mediated, at least in part, by reductions in the amount of abdominal fat. Regular physical exercise may prevent or ameliorate conditions associated with hyperinsulinemia including dyslipidemia, hypertension, and atherosclerosis in this group.

Weight loss, not aerobic exercise, improves pulmonary function in older obese men.

BACKGROUND: We evaluated the effect of weight loss (WL) or aerobic exercise (AEX) on pulmonary function in middle-aged and older (46-80 years) obese, sedentary men to determine the effect of reductions in body weight and increases in cardiorespiratory fitness on pulmonary function. METHODS: Subjects were randomly assigned to WL (n = 73), AEX (n = 71), or control (n = 26) groups. Maximal oxygen uptake (VO2max), body composition and anthropometrics, pulmonary function, and arterial blood gases were measured at baseline and after interventions. RESULTS: The 35 subjects who completed WL decreased weight by 11%, body fat percentage by 21% (p < .001), waist circumference by 8%, waist-hip ratio by 2%, and fat-free mass by 3% (p < .05). This resulted in a 3% increase in forced vital capacity (FVC) (4.08 +/- 0.71 L vs 4.21 +/- 0.76 L), a 5% increase in total lung capacity (6.62 +/- 0.99 L vs 6.94 +/- 0.99 L), an 18% increase in functional residual capacity (3.09 +/- 0.58 L vs 3.66 +/- 0.79 L), and an 8% increase in residual volume (2.20 +/- 0.44 L vs 2.37 +/- 0.52 L), with no change in forced expiratory volume in one second (FEV1), FEV1/FVC ratio, or carbon monoxide diffusing capacity. The change in FVC correlated with change in body weight (r = -.34, p < .05). The 38 subjects who completed AEX increased VO2max by 14%, with no change in pulmonary function. There were no changes in 8 control subjects. CONCLUSIONS: WL changes static lung volumes, not dynamic pulmonary function, in middle-aged and older, moderately obese, sedentary men. Some of the alterations in static lung function associated with aging may be due to the development of obesity and are modifiable by WL.

Cardiovascular fitness, body composition, and lipoprotein lipid metabolism in older men.

BACKGROUND: Lipoprotein lipids in older individuals are affected by family history of coronary artery disease (CAD), obesity, diet, and physical activity habits. METHODS: The relationship of obesity and physical fitness (VO2max) to lipoprotein lipids and postheparin lipases was examined in a cross-sectional study of 12 lean (LS) and 26 obese (OS) sedentary men and 18 master athletes (MAs) aged 65+/-1 years (mean +/- SE). The men were healthy, had no family history of CAD, and were weight stable on AHA diets at the time of study. RESULTS: VO2max was similar in LS and OS men but higher in the MAs. The OS men had a higher percentage of body fat (%BF), waist circumference, and waist:hip ratio (WHR) than the MA and LS men, but MA and LS men differed only in waist circumference. Total and LDL-C levels were comparable, but HDL-C, HDL2-C, and %HDL2b subspecies were higher in MAs than in OS and LS men, and in LS than in OS men. Triglyceride (TG) was similar in MAs and LS men but higher in OS men. Across groups, two multiple regression analyses models (VO2max, %BF, and WHR or waist circumference) showed that %BF and VO2max independently predicted HDL-C and HDL2, whereas WHR predicted TG (r2 = .45) more strongly than waist circumference (r2 = .39). Postheparin lipoprotein lipase activity (LPL) was comparable among groups and correlated independently with VO2max. Total postheparin lipolytic activity (PHLA), hepatic lipase activity (HL), and HL:PHLA ratio were similar in MAs and LS men but higher in OS men. In both multiple regression analysis models, only %BF predicted HL activity and the HL:PHLA ratio. The HL:PHLA ratio independently predicted HDL-C, HDL2-C, %HDL2b, %HDL3 subspecies, and the cholesterol:HDL-C ratio, whereas LPL activity predicted TG. CONCLUSIONS: Increased fitness and reduced total and abdominal fatness in MAs are associated with lower HL and higher LPL activities, which may mediate their higher HDL-C and lower TG levels relative to their sedentary peers.

Enhanced cardiovascular hemodynamics in endurance-trained postmenopausal women athletes.

PURPOSE: We sought to determine whether older women athletes who had habitually performed vigorous endurance exercise training had higher stroke volumes and cardiac outputs than sedentary postmenopausal women during maximal exercise. METHODS: Seventeen endurance-trained, postmenopausal women athletes (age 65 +/- 4 yr; VO2max 2.11 +/- 0.31 L x min(-1), 38.3 mL x kg(-1) x min(-1)) and 14 sedentary, postmenopausal women (age 63 +/- 5 yr; VO2max 1.41 +/- 0.22 L x min(-1), 23.7 +/- 3.5 mL x kg(-1) x min(-1)) performed maximal treadmill exercise while cardiac output (via acetylene rebreathing) and other cardiovascular hemodynamics were measured. Approximately half of the subjects in each group were on hormone replacement therapy (HRT). RESULTS: The greater VO2max of the athletes was the result of a greater cardiac output (12.8 +/- 1.6 vs. 9.3 +/- 1.4 L x min(-1)) resulting from their significantly larger stroke volume (80 +/- 10 vs 57 +/- 10 mL) at maximal exercise. There were no significant differences in maximal cardiac output or maximal stroke volume related to HRT status in the sedentary women or athletes. CONCLUSIONS: These data indicate that endurance-trained, competitive, postmenopausal women have higher stroke volumes and cardiac outputs during maximal exercise, than their sedentary peers. However, these data suggest that HRT may not affect maximal CV function in sedentary or endurance-trained postmenopausal women.