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Biomedical subjects

Andrew P Goldberg

Publications and source records attributed to Andrew P Goldberg.

At least 19 recordsLinked to original sources

High prevalence of abnormal glucose metabolism and poor sensitivity of fasting plasma glucose in the chronic phase of stroke.

BACKGROUND: Cardiovascular disease is the leading cause of death in long-term stroke survivors, and whole-body glucose metabolism is strongly linked to cardiovascular disease risk. This study provides important preliminary information on the prevalence of abnormal glucose metabolism in chronic stroke patients (mean 3 years after stroke) and reports on the utility of screening for abnormalities using fasting plasma glucose (FPG) in this population. METHODS: Two hundred and sixteen chronic hemiparetic stroke patients were screened for diabetes status by medical history and FPG. A subset (n = 80) was evaluated by oral glucose tolerance test to assess the utility of screening for abnormalities using FPG alone. RESULTS: Seventy-five of the 216 (35%) had type 2 diabetes by medical history. Another 70 were either diabetic (n = 11) or had impaired fasting glucose (n = 59) based on a single blood draw at the time of screening. FPG among non-diabetic stroke patients had a sensitivity of 49% for predicting abnormalities in the 2-hour glucose level during oral glucose tolerance test. Cumulative results identify 77% as abnormal (impaired or diabetic) on the basis of medical history, fasting plasma glucose, and/or 2-hour glucose level. CONCLUSIONS: The prevalence of abnormal glucose metabolism is extremely high in chronic stroke and is underestimated on the basis of FPG.

Aged↗

Effects of aerobic and resistive exercise training on glucose disposal and skeletal muscle metabolism in older men.

BACKGROUND: Aging is associated with insulin resistance, primarily as a result of physical inactivity and increased abdominal obesity. We hypothesized that aerobic (AEX) or resistive (RT) exercise training would result in comparable improvements in glucose disposal in older men, but that there would be different metabolic adaptations in skeletal muscle. METHODS: Thirty-nine older (63+/-1 years, mean+/-standard error of the mean), overweight and obese (body mass index=30.3+/-0.4 kg/m2) men were assigned to AEX (treadmill walking and/or jogging, n=19) or RT (upper and lower body, n=20) programs 3 d/wk for 6 months, with 9 completing AEX and 13 completing RT. Testing before and after the exercise programs included body composition, euglycemic-hyperinsulinemic clamps, and vastus lateralis muscle biopsies. RESULTS: Maximal oxygen consumption (VO2max) increased by 16% after AEX (p<.01), while leg and arm muscle strength increased by 45+/-5% and 27+/-5% after RT (p<.0001). Although participants were monitored to maintain their body weight during the exercise program, body weight decreased by 2% after AEX (p<.05), and increased by 2% after RT (p<.05). Whole-body glucose disposal, determined during the last 30 minutes of a 2-hour 480 pmol/m2/min euglycemic-hyperinsulinemic clamp, increased comparably by 20%-25% after AEX (51+/-5 to 61+/-5 microM/kgfat-free mass/min, p<.05) and RT (49+/-3 to 58+/-3 microM/kgfat-free mass/min, p<.05). The increase in vastus lateralis muscle glycogen synthase fractional activity in response to insulin stimulation was significantly higher after AEX compared to after RT (279+/-59% compared to 100+/-28% change, p<.05). Neither AEX nor RT altered muscle glycogen synthase total activity, glycogen content, or levels of phosphotidylinositol 3-kinase. CONCLUSION: These results suggest that AEX and RT result in comparable improvements in glucose metabolism in older men, whereas an increase in insulin activation of glycogen synthase occurred only with AEX. These improvements in insulin sensitivity could reduce the risk of metabolic syndrome and type 2 diabetes and attenuate the development of cardiovascular disease.

Age Factors↗

Acute-phase serum amyloid A: an inflammatory adipokine and potential link between obesity and its metabolic complications.

BACKGROUND: Obesity is associated with low-grade chronic inflammation, and serum markers of inflammation are independent risk factors for cardiovascular disease (CVD). However, the molecular and cellular mechanisms that link obesity to chronic inflammation and CVD are poorly understood. METHODS AND FINDINGS: Acute-phase serum amyloid A (A-SAA) mRNA levels, and A-SAA adipose secretion and serum levels were measured in obese and nonobese individuals, obese participants who underwent weight-loss, and persons treated with the insulin sensitizer rosiglitazone. Inflammation-eliciting activity of A-SAA was investigated in human adipose stromal vascular cells, coronary vascular endothelial cells and a murine monocyte cell line. We demonstrate that A-SAA was highly and selectively expressed in human adipocytes. Moreover, A-SAA mRNA levels and A-SAA secretion from adipose tissue were significantly correlated with body mass index (r = 0.47; p = 0.028 and r = 0.80; p = 0.0002, respectively). Serum A-SAA levels decreased significantly after weight loss in obese participants (p = 0.006), as well as in those treated with rosiglitazone (p = 0.033). The magnitude of the improvement in insulin sensitivity after weight loss was significantly correlated with decreases in serum A-SAA (r = -0.74; p = 0.034). SAA treatment of vascular endothelial cells and monocytes markedly increased the production of inflammatory cytokines, e.g., interleukin (IL)-6, IL-8, tumor necrosis factor alpha, and monocyte chemoattractant protein-1. In addition, SAA increased basal lipolysis in adipose tissue culture by 47%. CONCLUSIONS: A-SAA is a proinflammatory and lipolytic adipokine in humans. The increased expression of A-SAA by adipocytes in obesity suggests that it may play a critical role in local and systemic inflammation and free fatty acid production and could be a direct link between obesity and its comorbidities, such as insulin resistance and atherosclerosis. Accordingly, improvements in systemic inflammation and insulin resistance with weight loss and rosiglitazone therapy may in part be mediated by decreases in adipocyte A-SAA production.

Adipocytes↗

Treadmill exercise rehabilitation improves ambulatory function and cardiovascular fitness in patients with chronic stroke: a randomized, controlled trial.

BACKGROUND AND PURPOSE: Physical inactivity propagates disability after stroke through physical deconditioning and learned nonuse. We investigated whether treadmill aerobic training (T-AEX) is more effective than conventional rehabilitation to improve ambulatory function and cardiovascular fitness in patients with chronic stroke. METHODS: Sixty-one adults with chronic hemiparetic gait after ischemic stroke (>6 months) were randomized to 6 months (3x/week) progressive T-AEX or a reference rehabilitation program of stretching plus low-intensity walking (R-CONTROL). Peak exercise capacity (Vo2 peak), o2 consumption during submaximal effort walking (economy of gait), timed walks, Walking Impairment Questionnaire (WIQ), and Rivermead Mobility Index (RMI) were measured before and after 3 and 6 months of training. RESULTS: Twenty-five patients completed T-AEX and 20 completed R-CONTROL. Only T-AEX increased cardiovascular fitness (17% versus 3%, delta% T-AEX versus R-CONTROL, P<0.005). Group-by-time analyses revealed T-AEX improved ambulatory performance on 6-minute walks (30% versus 11%, P<0.02) and mobility function indexed by WIQ distance scores (56% versus 12%, P<0.05). In the T-AEX group, increasing training velocity predicted improved Vo2 peak (r=0.43, P<0.05), but not walking function. In contrast, increasing training session duration predicted improved 6-minute walk (r=0.41, P<0.05), but not fitness gains. CONCLUSIONS: T-AEX improves both functional mobility and cardiovascular fitness in patients with chronic stroke and is more effective than reference rehabilitation common to conventional care. Specific characteristics of training may determine the nature of exercise-mediated adaptations.

Aged↗

Human gender differences in fibrinolytic responses to exercise training and their determinants.

Endurance exercise training improves fibrinolysis, but this training-induced adaptation may differ somewhat between men and women. We sought to determine whether the potential gender differences in training-induced changes in selected fibrinolysis measures were related to changes in adiposity and/or plasma lipoprotein lipid levels. Seventeen men and 28 women, 50-75 years old, who were generally overweight to obese, were assessed for plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (t-PA) activity, t-PA antigen and plasma lipoprotein-lipid levels, and body composition before and after 6 months of endurance exercise training while on a low-fat diet. At baseline, there were no differences in fibrinolytic measures between the men and women. Baseline levels of these fibrinolytic markers in both men and women were primarily related to other fibrinolytic measures and body composition, with a smaller contribution from plasma high-density lipoprotein cholesterol (HDL-C) levels. Exercise training reduced t-PA antigen levels in both men and women, but the reduction was significantly greater in men (-1.6 +/- 0.3 versus -0.5 +/- 0.2 ng ml(-1), P = 0.007). Exercise training decreased PAI-1 activity more in men than in women (-2.6 +/- 1.4 versus +0.9 +/- 0.9 IU ml(-1), P = 0.03). Men and women both showed increased t-PA activity with exercise training to the same extent (+0.38 +/- 0.12 versus +0.36 +/- 0.24 U ml(-1)). The changes in fibrinolytic measures with exercise training in men and women were correlated with changes in other fibrinolytic measures, although in men abdominal fat changes were a strong predictor of fibrinolytic changes with training. These findings suggest that training-induced improvements in endogenous fibrinolysis markers are somewhat greater in men compared to women and may be more strongly associated with abdominal obesity in men.

Aged↗

Interleukin-6 genotype is associated with high-density lipoprotein cholesterol responses to exercise training.

BACKGROUND: High-density lipoprotein cholesterol (HDL-C) and its subfractions are modifiable with exercise training and these responses are heritable. The interleukin-6 (IL6)-174G/C polymorphism may be associated with HDL-C levels. We hypothesized that the IL6-174G/C polymorphism would be associated with plasma HDL-C response to exercise training. METHODS AND RESULTS: Sixty-five 50- to 75-year-olds on a standardized diet were studied before and after 24 weeks of aerobic exercise training. Significant differences existed among genotype groups for change with exercise training in HDL-C, HDL3-C, integrated HDL4,5NMR-C, and HDLsize. The CC genotype group increased HDL-C more than the GG (7.0 +/- 1.3 v. 1.0 +/- 1.1 mg/dL, p = 0.001) and GC groups (3.3 +/- 0.9 mg/dL, p = 0.02); for HDL3-C, the CC group increased more than the GG (6.1 +/- 1.0 v. 0.9 +/- 0.9, mg/dL p < 0.001) and GC groups (2.5 +/- 0.7 mg/dL, p = 0.006). Integrated HDL4,5NMR-C increased more in the CC than GG group (6.5 +/- 1.6 mg/dL v. 1.0 +/- 1.3 mg/dL, p = 0.01), as did HDLsize compared to the GG (CC: 0.3 +/- 0.1 v. GG: 0.1 +/- 0.1 nm, p = 0.02) and GC (0.0 +/- 0.0 nm, p = 0.007) groups. CONCLUSIONS: IL6 genotype is associated with HDL-C response to exercise training.

Aged↗

Repetitive bilateral arm training and motor cortex activation in chronic stroke: a randomized controlled trial.

CONTEXT: Reorganization in central motor networks occurs during early recovery from hemiparetic stroke. In chronic stroke survivors, specific rehabilitation therapy can improve upper extremity function. OBJECTIVE: To test the hypothesis that in patients who have chronic motor impairment following stroke, specific rehabilitation therapy that improves arm function is associated with reorganization of cortical networks. DESIGN, SETTING, AND PATIENTS: A randomized controlled clinical trial conducted in a US ambulatory rehabilitation program with 21 patients (median [IQR], 50.3 [34.8-77.3] months after unilateral stroke). Data were collected between 2001 and 2004. INTERVENTIONS: Patients were randomly assigned to bilateral arm training with rhythmic auditory cueing (BATRAC) (n = 9) or standardized dose-matched therapeutic exercises (DMTE) (n = 12). Both were conducted for 1 hour, 3 times a week, for 6 weeks. MAIN OUTCOME MEASURES: Within 2 weeks before and after the intervention, brain activation during elbow movement assessed by functional magnetic resonance imaging (fMRI) and functional outcome assessed using arm function scores. RESULTS: Patients in the BATRAC group but not in the DMTE group increased hemispheric activation during paretic arm movement (P = .03). Changes in activation were observed in the contralesional cerebrum and ipsilesional cerebellum (P = .009). BATRAC was associated with significant increases in activation in precentral (P<.001) and postcentral gyri (P = .03) and the cerebellum (P<.001), although 3 BATRAC patients showed no fMRI changes. Considering all patients, there were no differences in functional outcome between groups. When only BATRAC patients with fMRI response were included (n = 6), BATRAC improved arm function more than DMTE did (P = .02). CONCLUSIONS: These preliminary findings suggest that BATRAC induces reorganization in contralesional motor networks and provide biological plausibility for repetitive bilateral training as a potential therapy for upper extremity rehabilitation in hemiparetic stroke.

Aged↗

Racial differences in adipocyte size and relationship to the metabolic syndrome in obese women.

OBJECTIVE: To determine whether racial differences exist in the relationship of the abnormalities defining the metabolic syndrome (MS) to regional adiposity and fat cell size (FCS) in obese postmenopausal women. RESEARCH METHODS AND PROCEDURES: We determined the relationship of metabolic variables associated with the MS to regional body composition and abdominal (ABD) and gluteal (GLT) FCS in 25 white (CAU) and 25 African-American (AF-AMER) older women matched for age (58 +/- 5 years; mean +/- SD) and BMI (35 +/- 4 kg/m2). RESULTS: MS was present in 36% of the AF-AMER and 57% of the CAU women. There were no differences in total body, trunk, gluteofemoral fat mass or regional FCS, but AF-AMER women had 22% lower visceral fat, 24% higher insulin, and 31% lower triglyceride levels than CAU women (p < 0.05). Multiple regression analysis with body fat, visceral ABD fat area, and FCS as independent variables showed that GLT FCS was independently correlated with 2-hour insulin (r = 0.56), triglyceride (r = 0.62), and high-density lipoprotein cholesterol (r = -0.72) levels in AF-AMER women but not in CAU women, where only systolic blood pressure correlated with subcutaneous ABD fat area (r = 0.57) (p < 0.05). DISCUSSION: The associations between GLT FCS and metabolic dysfunction in obese AF-AMER but not CAU women suggest that central obesity is a less valid predictor of the MS in obese postmenopausal AF-AMER women than in CAU women and that GLT FCS may be a more sensitive indicator of risk for the MS in AF-AMER women.

Abdomen↗

Regulation of lipolysis and lipoprotein lipase after weight loss in obese, postmenopausal women.

OBJECTIVE: To test the hypothesis that the greater beta-adrenoceptor (beta-AR)-stimulated lipolysis and sensitivity (half-maximal lipolytic response) in abdominal (ABD) adipocytes, greater gluteal (GLT) adipose tissue-lipoprotein lipase (AT-LPL) activity, and dyslipidemia associated with obesity in older women are modifiable by weight loss (WL) and are not due to menopause or aging. RESEARCH METHODS AND PROCEDURES: The metabolic effects of 6 months of hypocaloric diet and low-intensity walking WL program on the regional regulation of in vitro lipolysis and AT-LPL activity in subcutaneous ABD and GLT adipocytes were measured in 34 obese (48.7 +/- 0.7% body fat, mean +/- SE) postmenopausal (59 +/- 1 years) white women. RESULTS: The lipolytic responsiveness to the beta-AR agonist isoproterenol and basal lipolysis in the presence of 1 U/mL adenosine deaminase-uninhibited (lipolysis) were greater (p < 0.01) in ABD than GLT adipocytes before and after WL, but there were no regional differences in postreceptor (dibutyryl 3',5'-cyclic adenosine monophosphate)-stimulated lipolysis. beta-AR sensitivity was greater in ABD than GLT adipocytes before (p < 0.01) but not after WL. Regional AT-LPL did not change after WL, but the change in the activity of ABD (but not GLT) AT-LPL correlated with the baseline adenosine deaminase-uninhibited lipolysis (r = 0.38, p = 0.03). There were no relationships between the declines in plasma triglyceride or increases in high-density lipoprotein cholesterol associated with WL and the changes in regional fat cell metabolism. DISCUSSION: Thus, despite improving lipoprotein lipid profiles in obese, postmenopausal women, WL does not affect the regulation of regional fat metabolism, and a greater tonic inhibition of basal lipolysis by endogenous adenosine may increase the activity of AT-LPL after WL and predispose older women to develop ABD adiposity.

Adipocytes↗

Association between body fat response to exercise training and multilocus ADR genotypes.

OBJECTIVE: To examine the contribution of adrenergic receptor (ADR) gene polymorphisms and their gene-gene interactions to the variability of exercise training-induced body fat response. RESEARCH METHODS AND PROCEDURES: This was an intervention study that used a volunteer sample of 70 healthy, sedentary men (n = 29) and postmenopausal women (n = 41) 50 to 75 years of age, with a BMI < or = 37 kg/m2, from the Washington, DC, metropolitan area. Participants completed 6 weeks of dietary stabilization (American Heart Association diet) before 24 weeks of supervised aerobic exercise training. Diet was maintained throughout the intervention. Change in percent total body fat, percent trunk fat, and fat mass by DXA in ADR genotype groups (Glu12/Glu9 alpha2b-ADR, Trp64Arg beta3-ADR, and Gln27Glu beta2-ADR) at baseline and after 24 weeks of aerobic exercise training was measured. RESULTS: In multivariate analysis (covariates: age, gender, and baseline value of phenotype), best fit models for percent total body and trunk fat response to exercise training retained main effects of all three ADR gene loci and the effects of each gene-gene interaction (p = 0.009 and 0.003, respectively). Similarly, there was a trend for the fat mass response model (p = 0.03). The combined genetic factors explained 17.5% of the overall model variability for percent total body fat, 22% for percent trunk fat, and 10% for fat mass. DISCUSSION: The body fat response to exercise training in older adults is associated with the combined effects of the Glu12/Glu9 alpha2b-, Trp64Arg beta3-, and Gln27Glu beta2-ADR gene variants and their gene-gene interactions.

Adipose Tissue↗

Metabolic effects of the addition of resistive to aerobic exercise in older men.

The metabolic changes associated with the addition of 4 months of resistive exercise to an existing aerobic exercise program (AEX+RT, n = 7) were compared to a maintenance aerobic exercise program (AEX, n = 8) in overweight, older men. The subjects in this study had recently completed a 6-month aerobic exercise program (treadmill walking, 45 min/d, 2 d/wk). The AEX+RT group added 6 exercises on upper- and lower-body pneumatic-resistance machines (2 sets, 15 repetitions each, 2 d/wk) to an aerobic exercise program at > or = 70% heart rate reserve for 30-40 min, 2 d/wk on treadmill, while the AEX group continued the same maintenance treadmill AEX program. There were no baseline differences in body weight, VO2max, or glucose metabolism between groups. The AEX+RT group increased upper- and lower-extremity strength by 28 +/- 4% and 46 +/- 6%, respectively (p < .05), despite a 9% decrease in VO2max (p < .05). VO2max did not change in the AEX group. There was no change in the fasting glucose or insulin levels, or the 3-h glucose responses to an oral glucose load in either group. The insulin responses decreased by 25 +/- 4% in the AEX+RT group (p < .01) but did not change in the AEX group. In conclusion, the addition of resistive exercise training to an existing aerobic exercise program may improve insulin sensitivity in overweight, older men, and thus prevent the development of type 2 diabetes.

Aged↗

High-density lipoprotein-cholesterol, its subfractions, and responses to exercise training are dependent on endothelial lipase genotype.

Plasma high-density lipoprotein cholesterol (HDL-C) levels are an important independent risk factor for cardiovascular disease (CVD) that can be modified through exercise training. However, levels of HDL-C and its subfractions and their response to standardized exercise training are highly variable among individuals. Such variability suggests that levels of HDL-C, its subfractions, and their response to exercise training may be influenced by genetic variation and the interaction of that genetic variation with physical activity. The endothelial lipase gene (LIPG) may influence HDL-C metabolism and has several recently identified genetic variants. We hypothesized that the LIPG Thr111Ile polymorphism would be associated with variation in HDL-C levels and its subfractions and their response to exercise training. Eighty-three sedentary, healthy 50- to 75-year-old subjects were weight-maintained on an American Heart Association Step 1 Diet and then studied before and after aerobic exercise training. Sample size varied according to outcome measure as complete data was not available for all subjects. Initial age, body composition, and maximum oxygen consumption (V02max) did not differ between LIPG genotype groups (CC, n=41 to 44; CT/TT, n=37 to 39). Initial total cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) levels were not significantly different between groups. The CT/TT group had lower initial HDL(2NMR)-C (12 +/- 1.0 v 17 +/- 1.1 mg/dL; P =.002) and integrated HDL(1,2NMR)-C (13 +/- 1.0 v 18 +/- 1.1 mg/dL; P=.002) levels and somewhat higher initial levels of integrated HDL(3,4,5)-C (31 +/- 2.2 v 25 +/- 2.3 mg/dL; P=.06). With exercise training, Vo2max increased, and body weight, total body fat, and visceral adipose tissue decreased similarly in both groups. With training, HDL-C levels increased twice as much (4.4 +/- 0.8 v 1.9 +/- 0.9 mg/dL; P=.04), HDL3-C levels increased almost 2-fold greater (3.8 +/- 0.7 v 2.2 +/- 0.6 mg/dL; P=.07), and HDL(5NMR)-C levels increased more than 4 times as much (2.2 +/- 0.8 v 0.5 +/- 0.6 mg/dL; P=.08) in the CC compared to the CT/TT group. We conclude that the LIPG genotype is associated with interindividual variability in HDL-C and its subfractions and their response to exercise training.

Adipose Tissue↗

Lifestyle intervention of hypocaloric dieting and walking reduces abdominal obesity and improves coronary heart disease risk factors in obese, postmenopausal, African-American and Caucasian women.

BACKGROUND: There are few empirical data to support the claim that weight loss improves coronary heart disease (CHD) risk factors in postmenopausal women; nor is it known if there are racial differences in changes of body fat distribution, lipids, glucose tolerance, and blood pressure with weight loss. This study determined the efficacy of a lifestyle weight loss intervention in reducing total and abdominal obesity and improving CHD risk factors in obese Caucasian and African-American postmenopausal women. METHODS: Body composition (dual-energy x-ray absorptiometry), abdominal fat areas (computed tomography scan), lipoprotein lipids, insulin, glucose tolerance, and blood pressure were measured before and after 6 months of hypocaloric diet and low-intensity walking in 76 overweight or obese (body mass index > 25 kg/m(2)), Caucasian (72%) or African-American (28%), postmenopausal (age = 60 +/- 5 years) women who completed the study. RESULTS: Absolute amount of body weight lost was similar in Caucasians (-5.4 +/- 3.6 kg) and African Americans (-3.9 +/- 3.6 kg), but Caucasian women lost relatively more fat mass (p <.05). Both groups decreased their subcutaneous abdominal fat, and Caucasian women decreased their visceral fat area, but there were no racial differences in the magnitude of abdominal fat lost. The intervention decreased triglyceride and increased high-density lipoprotein and high-density lipoprotein 2 cholesterol in both races, and it decreased total and low-density lipoprotein cholesterol in Caucasian women (p <.05-.0001). Fasting glucose and glucose area during the oral glucose tolerance test decreased (p <.0001) in Caucasian women, whereas insulin area decreased in both Caucasian (p <.01) and African-American (p <.05) women. Blood pressure decreased the most in women with higher blood pressures at baseline. Changes in lipids, fasting glucose and insulin, their responses during the oral glucose tolerance test, and blood pressure were not different between racial groups. CONCLUSIONS: Weight loss achieved through a lifestyle intervention of energy restriction and increased physical activity is an equally effective therapy in African-American and Caucasian obese, postmenopausal women for improving glucose and lipid CHD risk factors.

Abdomen↗

Sleep-disordered breathing and insulin resistance in middle-aged and overweight men.

Sleep-disordered breathing is a prevalent condition associated with impairment of daytime function and may predispose individuals to metabolic abnormalities independent of obesity. The primary objective of this study was to determine the metabolic consequences and community prevalence of sleep-disordered breathing in mildly obese, but otherwise healthy, individuals. One hundred and fifty healthy men, without diabetes or cardiopulmonary disease, were recruited from the community. Measurements included polysomnography, a multiple sleep latency test, an oral glucose tolerance test, determination of body fat by hydrodensitometry, and fasting insulin and lipids. The prevalence of sleep-disordered breathing, depending on the apnea-hypopnea index (AHI) cutoff, ranged from 40 to 60%. After adjusting for body mass index (BMI) and percent body fat, an AHI gt-or-equal, slanted 5 events/h was associated with an increased risk of having impaired or diabetic glucose tolerance (odds ratio, 2.15; 95% CI, 1.05-4.38). The impairment in glucose tolerance was related to the severity of oxygen desaturation (DeltaSa(O(2))) associated with sleep-disordered breathing. For a 4% decrease in oxygen saturation, the associated odds ratio for worsening glucose tolerance was 1.99 (95% CI, 1.11 to 3.56) after adjusting for percent body fat, BMI, and AHI. Multivariable linear regression analyses revealed that increasing AHI was associated with worsening insulin resistance independent of obesity. Thus, sleep-disordered breathing is a prevalent condition in mildly obese men and is independently associated with glucose intolerance and insulin resistance.

Adult↗

Comparing brain activation associated with isolated upper and lower limb movement across corresponding joints.

It was shown recently that functional activation across brain motor areas during locomotion and foot movements are similar but differ substantially from activation related to upper extremity movement (Miyai [2001]: Neuroimage 14:1186-1192). The activation pattern may be a function of the behavioral context of the movement rather than of its mechanical properties. We compare motor system activation patterns associated with isolated single-joint movement of corresponding joints in arm and leg carried out in equal frequency and range. Eleven healthy volunteers underwent BOLD-weighted fMRI while performing repetitive elbow or knee extension/flexion. To relate elbow and knee activation to the well-described patterns of finger movement, serial finger-to-thumb opposition was assessed in addition. After identifying task-related voxels using statistical parametric mapping, activation was measured in five regions of interest (ROI; primary motor [M1] and somatosensory cortex [S1], premotor cortex, supplementary motor area [SMA] divided into preSMA and SMA-proper, and cerebellum). Differences in the degree of activation across ROIs were found between elbow and knee movement. SMA-proper activation was prominent for knee, but almost absent for elbow movement (P < 0.05); finger movement produced small but constant SMA-proper activation. Ipsilateral M1 activation was detected during knee and finger movement, but was absent for the elbow task (P < 0.05). Knee movement showed less lateralization in M1 and S1 than other tasks (P < 0.05). The data demonstrate that central motor structures contribute differently to isolated elbow and knee movement. Activation during knee movement shows similarities to gait-related activation patterns.

Adult↗

Changes in high-density lipoprotein-cholesterol subfractions with exercise training may be dependent on cholesteryl ester transfer protein (CETP) genotype.

We sought to determine if a cholesteryl ester transfer protein (CETP) gene locus variation contributes to the variability in the responses of plasma high-density lipoprotein-cholesterol (HDL-C) and its subfractions to endurance exercise training. Middle- to older-aged men and women with at least 1 lipoprotein-lipid risk factor underwent 6 months of endurance exercise training while on a low-fat diet. Plasma lipid levels were measured by nuclear magnetic resonance (NMR). Initial age, body composition, lipoprotein-lipid profiles, and VO(2)max did not differ between the 2 CETP genotype groups (B1B1, n = 16; B1B2, n = 14). With exercise training, VO(2)max increased, and body weight, total body fat, and computed tomographic (CT) intra-abdominal visceral fat decreased similarly in both CETP genotype groups. Plasma total cholesterol and low-density lipoprotein-cholesterol (LDL-C) levels did not change significantly with training in either genotype group. HDL(2NMR)-C levels increased with exercise training in CETP B1B1 (P <.05), but did not change in CETP B1B2 genotype individuals. HDL(3NMR)-C levels tended to decrease with training in CETP B1B1 persons and HDL(4NMR)-C levels tended to increase with training somewhat more in CETP B1B2 individuals, but these differences were not significant. HDL(5NMR)-C levels increased similarly with exercise training in the 2 groups. The integrated HDL(3-5NMR)-C levels increased with exercise training in CETP B1B2 (P <.05), but did not change in CETP B1B1 genotype individuals. Apolipoprotein E (APO E) or lipoprotein lipase (LPL) PvuII genotype did not associate with HDL-C subfraction changes with training. Thus, CETP genotype may contribute to the interindividual differences in plasma HDL-C subfraction changes occurring with endurance exercise training in sedentary middle- to older-aged men and women.

Apolipoproteins E↗

Effects of apolipoprotein E genotype on dietary-induced changes in high-density lipoprotein cholesterol in obese postmenopausal women.

Lipid responses to a dietary intervention are highly variable between individuals. Part of this variation may be accounted for by individual differences in lipid-regulating genes that interact with diet to induce changes in lipoprotein metabolism. This study determined whether apolipoprotein E (APOE) genotype affects lipid responses to a low-fat, low-cholesterol diet in obese, postmenopausal women. Body weight and lipoprotein lipid responses to a 10-week, dietary intervention (American Heart Association [AHA] Step I) were compared in 61 women with the APOE 2/3 and APOE 3/3 genotype (APOE4-) and 18 women with the APOE 3/4 genotype (APOE4+) of a similar age, body composition, and maximal aerobic capacity. Body weight decreased by 2% in both groups, but changes in body weight correlated only with changes in low-density lipoprotein-cholesterol (LDL-C) (r =.27, P <.05). The dietary intervention decreased total cholesterol and LDL-C to a similar degree in both genotype groups. However, APOE4- women decreased high-density lipoprotein-cholesterol (HDL-C) by 17% +/- 11% and increased triglycerides by 20% +/- 41% in response to the diet, while APOE4+ women had a smaller decrease in HDL-C (-8% +/- 12%) and no change in plasma triglyceride. These group differences were significant for HDL-C (P <.01) and approached significance for triglycerides (P =.08). Moreover, APOE4- women decreased HDL(2)-C by 32% +/- 45%, while APOE4+ women increased HDL(2)-C by 12% +/- 62% (P <.01 between groups). It may be prudent to genotype older women before initiating low-fat diet therapy, as those with the APOE4 allele benefit the most, while the lipid profile could worsen in women without the APOE4 allele.

Aged↗

The effect of endurance exercise training on plasma lipoprotein AI and lipoprotein AI:AII concentrations in sedentary adults.

The effect of 6 months of endurance exercise training on plasma concentrations of lipoprotein (Lp)AI and LpAI:AII was determined in 39 sedentary subjects (17 men, 22 women, average age, 57 years) with abnormal cholesterol concentrations (total cholesterol [TC] > 200 mg/dL, or high-density lipoprotein-cholesterol [HDL-C] < 35 mg/dL). Following exercise training, plasma LpAI concentrations increased (+5.9 +/- 1.2 mg/dL; P <.001), but there was no change in total apolipoprotein (apo) A-I or LpAI:AII concentrations. The change in plasma LpAI concentration was positively correlated to changes in total HDL-C (r =.495, P =.001), the sum of HDL4-C(nmr) + HDL5-C(nmr) (r =.417, P =.008), and average HDL particle size (r =.415, P =.009), but not to changes in body composition or Vo2max. In the 8 subjects with the greatest change in LpAI concentration following training, the size distribution of LpAI and LpAI:AII particles in plasma also was measured before and after training. In these subjects, the size distribution of LpAI:AII particles did not change with training, but there was a significant increase (0.1 nm; P =.048) in the peak size of the "medium" (7.8 to 9.8 nm) LpAI particles after training. In 7 subjects who served as age- and weight-matched sedentary controls, plasma concentrations of total apo A-I, the LpAI and LpAI:AII subfractions, and plasma lipoprotein-lipids did not differ significantly between baseline and final testing. These data indicate that endurance exercise training increases the average size and plasma concentrations of LpAI, but not LpAI:AII, particles, which may represent possible enhancements of reverse cholesterol transport and may provide insight into the role that exercise plays in reducing cardiovascular disease risk.

Aged↗