Reduced LPL and subcutaneous lipid storage capacity are associated with metabolic syndrome in postmenopausal women with obesity.

OBJECTIVES: This study examines the hypothesis that lower adipose tissue lipoprotein lipase (LPL) activity and a limited capacity for subcutaneous adipocyte expansion will be associated with metabolic syndrome (MSyn) in postmenopausal women who are overweight and obese. METHODS: Women (N = 150; age 60 ± 1 year; BMI: 31.5 ± 0.3 kg m-2; mean ± standard errors of the means [SEM]) with and without MSyn had dual-energy X-ray absorptiometry scans for total body fat, CT scans for visceral and subcutaneous abdominal adipose tissue areas, lipid and glucose metabolic profiles, and abdominal and gluteal fat aspirations for subcutaneous fat cell weight (FCW; N = 150) and LPL activity (N = 100). RESULTS: Women with MSyn had similar total body fat, but 15% larger abdominal and 11% larger gluteal FCWs and more visceral fat (179 ± 7 vs. 134 ± 6 cm2) than women without MSyn (P's < 0.05). Abdominal LPL activity was 13% (P = 0.18) lower in women with than without MSyn and correlated with abdominal FCW (r = 0.49, P < 0.01) only in those without MSyn. Visceral fat and abdominal and gluteal FCWs correlated with MSyn components, and subcutaneous adipose tissue correlated with abdominal FCW (r = 0.43, P < 0.01) and LPL activity (r = 0.18, P < 0.05), independent of total body fat. CONCLUSIONS: These results show that women with MSyn have lower LPL activity, limited capacity for subcutaneous adipocyte lipid storage and greater ectopic fat accumulation in viscera than women without MSyn of comparable obesity. This suggests that the development of novel therapies that would enhance adipocyte expandability might prevent the accumulation of ectopic fat and reduce the risk for MSyn in postmenopausal women with obesity.

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.

Weight gain and adipose tissue metabolism after smoking cessation in women.

BACKGROUND: Cigarette smoking increases the risk of cardiovascular disease, and is an important preventable cause of death and illness. One major deterrent to smoking cessation is a gain in body weight. Understanding the mechanisms that contribute to this weight gain may maximize the success of long-term smoking cessation. We hypothesized that smoking cessation is associated with an increase in adipose tissue lipoprotein lipase (AT-LPL) activity and/or a decrease in lipolysis, two metabolic factors that determine the balance between fat storage and fat utilization, and thus affect the propensity for weight gain. MATERIALS AND METHODS: Ten premenopausal women (37.1+/-6.2 y, 31.7+/-6.4 kg/m(2) body mass index (BMI), mean+/-s.d.) participated in a 4 week smoking cessation program. Measurements of body weight, waist and hip circumferences, adipose cell metabolism and resting metabolic rate were obtained at baseline and after 4 weeks of smoking cessation. RESULTS: Of the 10 women who began the intervention, five successfully completed the smoking cessation intervention. After 4 weeks of smoking cessation, there were significant increases in body weight (95.1+/-13.9-97.7+/-14.4 kg, P<0.05), with no change in waist and hip circumferences or resting energy expenditure. Gluteal AT-LPL activity significantly increased in all women by 2.8-fold (1.65+/-1.30-4.72+/-3.34 nmol/g/min, P<0.05). Abdominal AT-LPL activity increased in four out of the five women, but did not reach statistical significance (1.14+/-0.88-3.50+/-3.76 nmol/g/min, P=0.14). The increase in body weight correlated with the increase in gluteal AT-LPL activity (r=0.89, P<0.05), as well as the baseline activity of gluteal AT-LPL (r=0.86, P=0.06). There were no changes in basal or stimulated lipolysis in the gluteal or abdominal fat depots. CONCLUSIONS: These results suggest that smoking cessation is associated with significant increases in body weight, as well as changes in adipose cell metabolism, in particular increases in AT-LPL activity. This increase in LPL activity may contribute to the increase in body weight associated with smoking cessation.

Treadmill training improves fitness reserve in chronic stroke patients.

OBJECTIVE: To investigate the hypothesis that treadmill training will improve peak fitness, while lowering the energy cost of hemiparetic gait in chronic stroke patients. DESIGN: Noncontrolled exercise intervention study with repeated-measures analysis. SETTING: Hospital-based senior exercise research center. PARTICIPANTS: Twenty-three patients (mean age +/- standard deviation [SD] 67 +/- 8 yr) with chronic hemiparetic gait after remote (>6 mo) ischemic stroke. INTERVENTION: Three 40-minute sessions of treadmill exercise weekly for 6 months. MAIN OUTCOME MEASURES: Peak exercise capacity (VO2peak) and rate of oxygen consumption during submaximal effort treadmill walking (economy of gait) by open circuit spirometry and ambulatory workload capacity before and after 3 and 6 months of training. RESULTS: Patients who completed 3 months of training (n = 21) increased their VO2peak +/- SD from 15.4 +/- 2.9 mL x kg(-1) x min(-1) to 17.0 +/- 4.4 mL x kg(-1) x min(-1) (p <.02) and lowered their oxygen demands of submaximal effort ambulation from 9.3 +/- 2 mL x kg(-1) x min(-1) to 7.9 +/- 1.5 mL x kg(-1) x min(-1) (p =.002), which enabled them to perform the same constant-load treadmill task using 20% less of their peak exercise capacity (62.3% +/- 17.2% vs 49.9% +/- 19.3%, p <.002). Gains in VO2peak and economy of gait plateaued by 3 months, while peak ambulatory workload capacity progressively increased by 39% (p <.001) over 6 months. CONCLUSIONS: Treadmill training improves physiologic fitness reserve in chronic stroke patients by increasing VO2peak while lowering the energy cost of hemiparetic gait, and increases peak ambulatory workload capacity. These improvements may enhance functional mobility in chronic stroke patients.

Exercise rehabilitation improves functional outcomes and peripheral circulation in patients with intermittent claudication: a randomized controlled trial.

OBJECTIVE: To determine the effects of a 6-month exercise program on ambulatory function, free-living daily physical activity, peripheral circulation, and health-related quality of life (QOL) in disabled older patients with intermittent claudication. DESIGN: Prospective, randomized controlled trial. SETTING: University Medical (Center and Veterans Affairs Medical Center, Baltimore, Maryland. PARTICIPANTS: Thirty-one of 61 patients with Fontaine stage II peripheral arterial occlusive disease (PAOD) were randomized to exercise rehabilitation and 30 to usual-care control. Three patients from the exercise group and six patients from the control group dropped out, leaving 28 and 24 patients, respectively, completing the study in each group. INTERVENTION: Six months of exercise rehabilitation. MEASUREMENTS: Treadmill distance walked to onset of claudication and to maximal claudication, ambulatory function, peripheral circulation, perceived QOL, and daily physical activity. RESULTS: Compliance with the exercise program was 73% of the possible sessions. Exercise rehabilitation increased treadmill distance walked to onset of claudication by 134% (P < .001) and to maximal claudication by 77% (P < .001), walking economy by 12% (P = .003), 6-minute walk distance by 12% (P < .001), and maximal calf blood flow by 30% (P < .001). Changes in distance walked to maximal pain correlated with changes in walking economy (r = -.50, P = .013) and changes in maximal calf blood flow (r = .38, P = .047). Exercise rehabilitation increased accelerometer-derived daily physical activity by 38% (P < .001); this change correlated with the change in distance walked to maximal pain (r = .45, P = .020). These improvements were significantly better than the changes in the control group (P < .05). CONCLUSION: Improvements in claudication following exercise rehabilitation in older PAOD patients are dependent on improvements in peripheral circulation and walking economy. Improvement in treadmill claudication distances in these patients translated into increased accelerometer-derived physical activity in the community, which enabled the patients to become more functionally independent.

[Surgical treatment of gastroduodenal ulcer hemorrhage]. / Khirurgicheskoe lechenie gastroduodenal'nykh krovotechenii iazvennoi étologii.

The results of treatment of patients with gastroduodenal ulcerous bleeding over 20-year period were analyzed. From 1997 active individualized policy was used in the treatment of 522 patients. In duodenal ulcer the drug-thermal vagotomy was applied as well as traditional organ-saving operations, in combination with extraduodenisation of ulcer when it penetrates into pancreatic head. In gastric ulcer sparing resection or methods of ulcer's taking outside gastrointestinal tract (extragastration of ulcer) with preservation of gastric angio-, and neuroarchitectonics were preferable. In preoperative period Sandostatin and Hystodil were applied, in postoperative period--Imunofan.

Insulin action after resistive training in insulin resistant older men and women.

OBJECTIVES: To determine the effects of resistive training (RT) on insulin action and assess the determinants of the changes in insulin action. DESIGN: Longitudinal study. SETTING: Outpatient setting. PARTICIPANTS: Eighteen older men and older postmenopausal women (65-74 years) with normal (6 men and 5 women) or impaired glucose tolerance (4 men and 3 women). INTERVENTION: Six months of progressive whole-body RT. MEASUREMENTS: Upper and lower body strength was assessed by the one repetition maximum test. Total body fat and fat-free mass (FFM) were determined by dual-energy x-ray absorptiometry before and after 6 months of RT. Insulin sensitivity was estimated from the relationship of glucose utilization (M) to the concentration of insulin (I) during the last 30 minutes of 3-hour hyperinsulinemic-euglycenic clamps (240 pmol x min(-2) x min(-1)) (M/I) before and after RT. RESULTS: RT significantly improved upper- and lower-body muscular strength (P < .005). FFM increased after RT in the entire group (P < .01) with no significant change in body fat. Although the change in M was larger in men (13%) than women (3%), the difference was not significant. The change in M was a function of initial M (r = -0.53, P < .05). There was a trend (0.060+/-0.006 vs 0.066+/-0.006 micromol x kg(-1) x min(-1)/pmol/l, n = 18) for M/I to increase after RT in the combined group of men and women (P = .06). There were no significant relationships between changes in M or M/I with changes in body composition or strength. CONCLUSION: A 6-month RT program tends to improve insulin action in insulin-resistant older adults. These results suggest that RT may be useful in ameliorating insulin resistance that often occurs with physical inactivity, obesity, and loss of muscular strength in older insulin resistant men and women.

Racial disparities in metabolism, central obesity, and sex hormone-binding globulin in postmenopausal women.

Increased total and intraabdominal fat (IAF) obesity as well as other metabolic conditions associated with the insulin resistance syndrome (IRS) are related to low levels of sex hormone-binding globulin (SHBG) in young and older Caucasian (CAU) and young African-American (AA) women. We examined whether postmenopausal AA women, a population with a high incidence of obesity and IRS despite low IAF, would have higher levels of circulating SHBG compared with CAU women, and whether there would be negative relationships between indexes of obesity and risk factors associated with IRS and SHBG levels. We measured body composition, SHBG, free testosterone, leptin, glucose tolerance, insulin, and lipoprotein lipids in 55 CAU (mean +/- SD, 59 +/- 7 yr) and 35 AA (57 +/- 6 yr) sedentary women of comparable obesity (48% body fat, by dual energy x-ray absorptiometry). Compared with CAU women, AA women had larger waist (101 vs. 96 cm), larger fat mass (44.9 +/- 8.8 vs. 39.9 +/- 8.1 kg), larger sc fat area (552 +/- 109 vs. 452 +/- 109 cm(2)), and lower IAF/SC ratio (0.28 +/- 0.12 vs. 0.38 +/- 0.15; P < 0.01), but similar waist to hip ratio (0.83). Both groups had similar SHBG (117 vs. 124 nmol/L) and free testosterone (3.7 vs. 3.4 pmol/L) levels, but AA women had a 35% higher leptin, 34% higher fasting insulin, and 39% greater insulin response to a glucose load (P < 0.05) compared with CAU women. In CAU, but not AA, women SHBG correlated negatively with body mass index (r = -0.28; P < 0.05), waist (r = -0.36; P = 0.01), IAF (r = -0.34; P = 0.01), and insulin response to oral glucose (r = -0.37; P < 0.05) and positively with high density lipoprotein cholesterol (r = 0.30; P = 0.03). The relationship between insulin area and SHBG in CAU women disappeared after adjusting for IAF, whereas the relationship between high density lipoprotein cholesterol and SHBG persisted after adjusting for IAF, but not for fat mass. Leptin was positively related to fat mass (P < 0.05) in both groups, but it was related to insulin only in the Caucasian women (P< 0.01). There was a racial difference in the slopes (P< 0.05) of the relationships of leptin to fat mass (P < 0.05). Racial differences in leptin disappeared after adjustment for fasting insulin. These results suggest that the metabolic relationships between total and regional obesity, glucose, and lipid metabolism with SHBG in CAU women are different from those in postmenopausal obese AA women.

Limited value of the homeostasis model assessment to predict insulin resistance in older men with impaired glucose tolerance.

OBJECTIVE: Insulin resistance (IR) in older individuals is associated with risk factors for coronary artery disease. The glucose clamp measures IR directly, but the homeostasis model assessment (HOMA) of IR, referred to here as HOMA-IR, is based on fasting glucose and insulin and is less invasive and labor intensive. This method requires validation in the elderly. RESEARCH DESIGN AND METHODS: We assessed the validity of HOMA-IR as an index of IR by comparing it to glucose infusion rates (GIRs) measured by a glucose clamp (600 pmol x m(-2) x min(-1)) in 45 obese men (61 +/- 8 years of age, mean +/- SD) with normal glucose tolerance (NGT) (n = 21) or impaired glucose tolerance (IGT) (n = 24). We also evaluated relationships between body composition, exercise capacity, and IR. RESULTS: Subjects with NGT had lower BMI (28 +/- 3 vs. 31 +/- 3 kg/m2), waist circumference (97 +/- 9 vs. 105 +/- 9 cm), waist-to-hip ratio (WHR) (0.93 +/- 0.06 vs. 0.97 +/- 0.05), and percent body fat (25 +/- 6 vs. 30 +/- 6) than subjects with IGT. Subjects with NGT also had lower areas above basal during the 2-h oral glucose tolerance test for glucose (274 +/- 95 vs. 419 +/- 124 mmol x min/l) and insulin (38,142 +/- 18,206 vs. 58,383 +/- 34,408 pmol x min/l) and lower HOMA-IR values (2.2 +/- 0.8 vs. 4.2 +/- 2.6) than subjects with IGT. GIR (micromol x kg(-1) FFM x min(-1)) was higher in subjects with NGT than in subjects with IGT (53 +/- 11 vs. 43 +/- 14). HOMA-IR correlated with GIR in subjects with NGT (r = -0.59), but not in subjects with IGT (r = -0.13). GIR correlated with VO2max in subjects with NGT (r = 0.58) and IGT (r = 0.42), but with WHR only in subjects with NGT (r = -0.53). HOMA-IR correlated with VO2max (r = -0.57) and waist circumference (r = 0.54) in subjects with NGT, but with percent body fat in subjects with IGT (r = 0.54). CONCLUSIONS: These findings indicate that HOMA-IR should not be used as an index of IR in older individuals who may be at risk for IGT, and suggest that lifestyle changes that increase VO2max and decrease body fat may reduce IR in older people.

Reductions in visceral fat during weight loss and walking are associated with improvements in VO(2 max).

The accumulation of visceral fat is independently associated with an increased risk for cardiovascular disease. The aim of this study was to determine whether the loss of visceral adipose tissue area (VAT; computed tomography) is related to improvements in maximal O(2) uptake (VO(2 max)) during a weight loss (250-350 kcal/day deficit) and walking (3 days/wk, 30-40 min) intervention. Forty obese [body fat 47 +/- 1 (SE) %], sedentary (VO(2 max) 19 +/- 1 ml. kg(-1). min(-1)) postmenopausal women (age 62 +/- 1 yr) participated in the study. The intervention resulted in significant declines in body weight (-8%), total fat mass (dual-energy X-ray absorptiometry; -17%), VAT (-17%), and subcutaneous adipose tissue area (-17%) with no change in lean body mass (all P < 0.001). Women with an average 10% increase in VO(2 max) reduced VAT by an average of 20%, whereas those who did not increase VO(2 max) decreased VAT by only 10%, despite comparable reductions in body fat, fat mass, and subcutaneous adipose tissue area. The decrease in VAT was independently related to the change in VO(2 max) (r(2) = 0.22; P < 0. 01) and fat mass (r(2) = 0.08; P = 0.05). These data indicate that greater improvements in VO(2 max) with weight loss and walking are associated with greater reductions in visceral adiposity in obese postmenopausal women.

Self-efficacy targeted treatments for weight loss in postmenopausal women.

Matching behavioral treatment programs to different types of obese clients is a rarely studied strategy, thus guidelines for identifying who might benefit most from which program remain elusive. This study categorized the weight control self-efficacy beliefs of obese, postmenopausal women, and determined the effects of self-efficacy targeted versus non-targeted (control) treatment on weight loss outcomes (body habitus, physical conditioning, affect, and eating behaviors). Obese (BMI 33 +/- 5), postmenopausal (60 +/- 6 years old) women (n = 59) participated in a 6-month weight loss program. The 37 women categorized by Q methodology as Assured (self-confident, independent) were randomized to Assured (AT) or Non-Targeted (NT) treatment; the 22 Disbelievers (doubtful, wavering) were randomized to Disbeliever (DT) or NT treatment. At baseline, the Assureds had significantly smaller body girths and reported significantly greater self-esteem, fewer symptoms of binge eating, and less negative affect overeating than the Disbelievers. Improvement in these variables with weight loss erased significant differences between the groups and was a desired outcome. Treatment delivery type may have influenced attrition rate, since significantly more Assureds dropped from NT than AT and significantly more Disbelievers dropped from DT than NT. Thus, the self-efficacy type may serve as a means to identify different types of treatment needs (flexible vs. rigid) to sustain women's adherence and success in the program. The significant weight loss outcomes for women in all groups argues for the incorporation of strategies to enhance self-efficacy but not the need for specific treatments that directly target self-efficacy types.

Weight loss and exercise walking reduce pain and improve physical functioning in overweight postmenopausal women with knee osteoarthritis.

We conducted an uncontrolled pilot study to determine the effects of a weight loss and walking program on knee pain and physical function in overweight and obese (body mass index; BMI [kg/m] 25-29.9 and BMI > or = 30, respectively) postmenopausal women with knee osteoarthritis (OA). Forty-eight such women completed self-report (Western Ontario and McMaster University Osteoarthritis Index (WOMAC)) and performance-based measures of physical function ("up and go" test, 6-min walk) and enrolled in a 6-month intervention that included weekly nutrition classes and an exercise-walking program. The intervention produced an average weight loss of 5.6 +/- 4.0 kg in the 30 women who completed the program. There also were significant improvements in the 6-min walk and on VO(2max). Improvements in the timed up and go test and on the WOMAC pain and function scores, however, were restricted only to women who were classified as obese at baseline. These findings suggest that a 6-month weight loss and walking program improves measures of physical functioning and pain in overweight and obese postmenopausal women with knee OA. Among obese women, functional improvement correlated with weight loss, encouraging continued emphasis on weight loss for managing knee OA.

Improved functional outcomes following exercise rehabilitation in patients with intermittent claudication.

BACKGROUND: The purposes of this study were to identify predictors of increased claudication distances following exercise rehabilitation in peripheral arterial occlusive disease (PAOD) patients with intermittent claudication and determine whether improved claudication distances translated into increased free-living daily physical activity in the community setting. METHODS: Sixty-three patients were recruited (age, 68+/-1 years, mean +/- standard error). Patients were characterized on treadmill claudication distances, walking economy, peripheral circulation, cardiopulmonary function, self-perceived ambulatory function, body composition, baseline comorbidities, and free-living daily physical activity before and after a 6-month treadmill exercise program. RESULTS: Exercise rehabilitation increased distance to onset of claudication pain by 115% (178+/-22 m to 383+/-34 m; p < .001) and distance to maximal claudication pain by 65% (389+/-29 m to 641+/-34 m; p < .001). The increased distance to onset of pain was independently related to a 27% increase in calf blood flow (r = .42, p < .001) and to baseline age (r = -.26, p < .05), and the increased distance to maximal pain was predicted by a 10% increase in peak oxygen uptake (r = .41, p < .001) and by a 10% improvement in walking economy (r = -.34, p < .05). Free-living daily physical activity increased 31% (337+/-29 kcal/day to 443+/-37 kcal/day; p < .001) and was related to the increases in treadmill distances to onset (r = .24, p < .05) and to maximal pain (r = .45, p < .001). CONCLUSIONS: Increased claudication distances following exercise rehabilitation are mediated through improvements in peripheral circulation, walking economy, and cardiopulmonary function, with younger patients having the greatest absolute ambulatory gains. Furthermore, improved symptomatology translated into enhanced community-based ambulation.

Responses of adipose tissue lipoprotein lipase to weight loss affect lipid levels and weight regain in women.

This study determines whether changes in abdominal (ABD) and gluteal (GLT) adipose tissue lipoprotein lipase (LPL) activity in response to a 6-mo weight loss intervention, comprised of a hypocaloric diet and low-intensity walking, affect changes in body composition, fat distribution, lipid metabolism, and the magnitude of weight regain in 36 obese postmenopausal women. Average adipose tissue LPL activity did not change with an average 5.6-kg weight loss, but changes in LPL activity were inversely related to baseline LPL activity (ABD: r = -0.60, GLT: r = -0.48; P < 0.01). The loss of abdominal body fat and decreases in total and low-density lipoprotein cholesterol were greater in women whose adipose tissue LPL activity decreased with weight loss despite a similar loss of total body weight and fat mass. Moreover, weight regain after a 6-mo follow-up was less in women whose adipose tissue LPL activity decreased than in women whose LPL increased (ABD: 0.9 +/- 0.5 vs. 2.8 +/- 0.6 kg, P < 0.05; GLT: 0.2 +/- 0.5 vs. 2.8 +/- 0.5 kg, P < 0.01). These results suggest that a reduction in adipose tissue LPL activity with weight loss is associated with improvements in lipid metabolic risk factors with weight loss and with diminished weight regain in postmenopausal women.

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.

Lipoprotein lipase gene variation is associated with adipose tissue lipoprotein lipase activity, and lipoprotein lipid and glucose concentrations in overweight postmenopausal women.

Adipose tissue lipoprotein lipase (LPL) activity is under strong genetic control in both mice and humans. This study determines whether common DNA variation in the LPL gene (PvuII and HindIII polymorphisms) is associated with adipose tissue LPL activity and metabolic risk factors in a homogeneous population of 75 overweight postmenopausal women (body mass index >25 kg/m2; age: 51-69 years old). The allele frequencies for the presence of the cut-sites for LPL HindIII and PvuII were 0.71 and 0.49, respectively. There were no associations between the HindIII polymorphism and any of the measured variables. Age, body mass index, percent body fat, waist-hip ratio, visceral and subcutaneous fat area, and gluteal (GLT) and abdominal (ABD) adipocyte size did not differ by LPL PvuII genotype. However, adipose tissue LPL activity at both GLT and ABD sites was higher in women without the LPL PvuII cut-site (-/-) compared with women who were heterozygous (+/-) or homozygous (+/+) for the cut-site (P<0.05). Total and LDL cholesterol were lower in women without the LPL PvuII cut-site (-/-) compared with women who were heterozygous or homozygous for the cut-site (P<0.05), whereas triglyceride and HDL levels were similar between LPL PvuII genotypes. Fasting glucose, but not insulin, was lower in women without the LPL PvuII cut-site (-/-). These data suggest that the LPL PvuII polymorphism is a possible marker for a functional mutation that is found in the LPL gene and that alters LPL activity in older overweight women.

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.

Leptin responses to weight loss in postmenopausal women: relationship to sex-hormone binding globulin and visceral obesity.

OBJECTIVE: Leptin concentrations increase with obesity and tend to decrease with weight loss. However, there is large variation in the response of serum leptin levels to decreases in body weight. This study examines which endocrine and body composition factors are related to changes in leptin concentrations following weight loss in obese, postmenopausal women. RESEARCH METHODS AND PROCEDURES: Body composition (DXA), visceral obesity (computed tomography), leptin, cortisol, insulin, and sex hormone-binding globulin (SHBG) concentrations were measured in 54 obese (body mass index [BMI] = 32.0+/-4.5 kg/m2; mean +/- SD), women (60+/-6 years) before and after a 6-month hypocaloric diet (250 to 350 kcal/day deficit). RESULTS: Body weight decreased by 5.8+/-3.4 kg (7.1%) and leptin levels decreased by 6.6+/-11.9 ng/mL (14.5%) after the 6-month treatment. Insulin levels decreased 10% (p< 0.05), but mean SHBG and cortisol levels did not change significantly. Relative changes in leptin with weight loss correlated positively with relative changes in body weight (r = 0.50, p<0.0001), fat mass (r = 0.38, p<0.01), subcutaneous fat area (r = 0.52, p<0.0001), and with baseline values of SHBG (r = 0.38, p<0.01) and baseline intra-abdominal fat area (r = -0.27, p<0.06). Stepwise multiple regression analysis showed that baseline SHBG levels (r2 = 0.24, p<0.01), relative changes in body weight (cumulative r2 = 0.40, p<0.05), and baseline intra-abdominal fat area (cumulative r2 = 0.48, p<0.05) were the only independent predictors of the relative change in leptin, accounting for 48% of the variance. DISCUSSION: These results suggest that obese, postmenopausal women with a lower initial SHBG and more visceral obesity have a greater decrease in leptin with weight loss, independent of the amount of weight lost.

Changes in plasma leptin and insulin action with resistive training in postmenopausal women.

OBJECTIVE: To determine the effects of 16 weeks of resistive training alone (RT) and with weight loss (RT+WL) on insulin action, plasma leptin concentrations and leptin's relationship to beta-cell sensitivity to glucose, resting metabolic rate (RMR), and plasma catecholamines in older women. SUBJECTS: Fifteen obese postmenopausal women aged 50-69 y. MEASUREMENTS: Body composition (by dual-energy X-ray absorptiometry), RMR (by indirect calorimetry), insulin action (by 2 h hyperglycemic clamps; 7.9 mmol/l above basal plasma glucose levels), plasma leptin and insulin (by RIA), and plasma catecholamines (by enzymatic methods). RESULTS: RT and RT+WL resulted in significant improvements in muscular strength (P<0.01) with no changes in maximal oxygen consumption. Body weight, fat mass and percent body fat did not change with RT, but decreased with RT+WL (P<0.001). Fat-free mass and RMR increased after training when both groups were combined (P<0.05). The insulin response during the last 20 min of the 2 h hyperglycemic clamps decreased 16% after RT (P=0.05), 43% after RT+WL (P<0.05), and 29% in the entire group (P<0. 01) without any changes in glucose utilization. Plasma leptin levels did not change after RT, but decreased by 36% after RT+WL (P<0.05). Baseline leptin levels correlated with body weight (r=0.68, P<0.01), body fat mass (r=0.77, P<0.001), and RMR (kcal/d; (r=0.69, P<0.005), but not with baseline norepinephrine or epinephrine levels. Plasma leptin levels correlated with basal insulin (r=0.73, P<0.005), and approached significance with the 0-10 min and 100-120 min insulin response to hyperglycemia before training (both r=0.51, P=0.07). In the entire group, the change in insulin response from 100-120 min during the clamp correlated with the change in leptin levels (r=0.60, P<0.05), but this was not independent of changes in fat mass. CONCLUSIONS: Although changes in leptin levels were not related to changes in RMR or plasma catecholamines after RT with and without weight loss, the increase in insulin action after training and weight loss may be related to the decrease in leptin levels that were mediated by the loss of body fat in the obese, postmenopausal women. International Journal of Obesity (2000)24, 27-32