Visceral adipose tissue measured by DXA correlates with measurement by CT and is associated with cardiometabolic risk factors in children.

BACKGROUND: Visceral adipose tissue (VAT) generally demonstrates a stronger relationship with cardiometabolic risk factors than total body fat or subcutaneous adipose tissue. OBJECTIVES: The purpose of this study was to compare VAT estimated in children by total volume dual-energy X-ray absorptiometry (DXA) with a gold standard measurement, single slice (L4-L5) computed tomography (CT). METHODS: A total of 329 (152 females, 177 males) children ages 6-18 years (mean age 12.3 ± 3.6) and with average body mass index percentile of 54.9% (3-99%) had their VAT estimated by both CT and DXA. Linear association between methods was measured using Pearson's correlation. Multiple linear regressions compared the associations between cardiometabolic risk factors and both CT-VAT and DXA-VAT, respectively. RESULTS: In children, DXA-VAT was correlated significantly with CT-VAT, with a stronger relationship in overweight and obese children. Multiple regression analysis showed that both estimates of VAT were significantly associated with lipids and insulin sensitivity, measured by euglycaemic-hyperinsulinaemic clamp. Additionally, DXA-VAT was associated with diastolic blood pressure, homeostasis model of insulin resistance and fasting insulin, but CT-VAT was not. CONCLUSION: In children, total volume DXA-VAT and single slice CT-VAT are significantly correlated and each demonstrates similar associations with cardiometabolic risk factors. This suggests that DXA is a useful and valid method for estimation of VAT in children.

The relative contributions of the abdominal visceral and subcutaneous fat depots to cardiometabolic risk in youth.

The aim of this study was to evaluate the association of abdominal visceral and subcutaneous fat, independent of total body fat, with cardiometabolic risk factors and insulin resistance among youth. Visceral and subcutaneous fat, percentage total body fat, insulin resistance (adjusted for lean body mass: Mlbm), blood pressure, glucose, insulin and lipids were obtained in 472 youth ages 6-18 years. Linear regression, adjusted for age, sex, race, Tanner stage and percentage total body fat, was used to evaluate associations of visceral and subcutaneous fat with cardiometabolic risk factors. Visceral fat was associated inversely with Mlbm (P = 0.003) and positively with fasting insulin (P = 0.002) and triglycerides (P = 0.002). Visceral fat levels above the mean were associated inversely with high-density lipoprotein (HDL) cholesterol (P = 0.002), and positively with systolic blood pressure (P < 0.0001) and non-HDL cholesterol (P < 0.0001). Subcutaneous fat was associated inversely with Mlbm (P = 0.003) and HDL cholesterol (P < 0.05), and positively with fasting glucose (P < 0.05), fasting insulin (P = 0.0003), systolic blood pressure (P = 0.005) and triglycerides (P = 0.003). Subcutaneous fat levels above the mean were associated with non-HDL cholesterol (P = 0.0002). These findings suggest that there may be a threshold level of visceral and subcutaneous fat (regardless of total body fat), that when exceeded in childhood, is more likely to be associated with many cardiometabolic risk factors. Triglycerides and insulin resistance appear to be associated with these fat depots at even lower thresholds of abdominal adiposity.

Bone mineral deficits in recipients of hematopoietic cell transplantation: the impact of young age at transplant.

Low bone mineral density (BMD) has been reported in recipients of pediatric hematopoietic cell transplantation (HCT), but it is unclear whether age at HCT has a role. The objective of this cross-sectional study was to determine if patients treated with HCT before the age of 10 years have long-term BMD deficits compared with patients transplanted at an older age and with sibling controls. The study included 151 HCT recipients (87 males), age at study 24.7±8.6 years treated with HCT for hematologic malignancies at age 10.9±6.4 years, and 92 healthy sibling controls (49 males), age at study 22.3±8.0 years. Dual-energy x-ray absorptiometry was performed to measure BMD Z-scores for total body BMD (TBMD), lumbar spine BMD (LBMD) and femoral neck BMD (FNBMD, for subjects 20 years at study visit). Patients <10 years at HCT had significantly lower TBMD and FNBMD Z-scores (by 0.5 and 0.8 s.d., respectively) compared with controls (P=0.003 and P=0.0001, respectively) and patients >18 years at HCT (P=0.04 and P=0.004, respectively) at an average of 14 years after HCT. In conclusion, this study identified young age at transplant as an important risk factor for bone deficits in young adulthood, suggesting that efforts to reduce bone loss should focus on this patient population.

Effects of left ventricular assist device (LVAD) placement on myocardial oxidative stress markers.

PURPOSE: The primary purpose of this study was to examine the changes in myocardial oxidative stress during the support of a left ventricular assist device (LVAD). METHODS: Myocardial tissue was collected from the lower left ventricle of 15 adult subjects with class IV heart failure (HF) during LVAD placement (n=9) or LVAD removal (Post-LVAD; n=6). Each tissue sample was separated into cytosolic and myofibrillar subfractions and analysed for protein content and carbonylation. RESULTS: The myofibrillar proteins in the HF subjects had a significantly lower (p=0.008) level of protein carbonylation when compared to the myofibrillar proteins in Post-LVAD patients at 1.630±0.277 and 3.075±0.413 optical density, respectively. The level of protein carbonylation in myosin and actin were lower in HF (myosin: 1406.22±218.45, actin: 436±79.72 optical density) subjects compared to Post-LVAD (myosin: 2280.5±441.26, actin: 804.67±155.71 optical density) subjects (p=0.035 and p=0.018, respectively). However, once the extent of carbonylation in the myosin and actin bands were normalised to the amount of protein content, all significant difference was lost (HF moysin: 1823.89±413.42, Post-LVAD myosin: 1330.33±297.10 optical density, p=0.199 and HF actin: 3755.78±349.59, Post-LVAD actin: 4402.83±666.51 optical density, p=0.182). There was no significant difference in the cytosolic subfractions before or after normalisation of protein content. CONCLUSION: Carbonylation is elevated in the myocardium of HF and Post-LVAD subjects and it appears that LVAD support does not affect the level of myocardial oxidative stress.

Changes in inflammatory biomarkers following one-year of moderate resistance training in overweight women.

BACKGROUND: Overweight individuals commonly demonstrate elevated levels of inflammatory and cell adhesion molecules. Elevated levels of inflammation and adhesion have been implicated in the pathogenesis of cardiovascular disease. Aerobic exercise has been shown to be effective in altering specific biomarkers of inflammation and cell adhesion; however, little is known regarding the effects of resistance training (RT) on these biomarkers. This study examined the effects of 1 year of moderate-intensity RT on biomarkers of inflammation and adhesion in healthy, overweight women. METHODS AND RESULTS: Participants included 28 (12 control, 16 RT) overweight (body mass index>or=25 kg/m2) women, aged 25-44 years, studied before and after 1 year of RT. C-reactive protein (CRP), interleukin-6 (IL-6), adiponectin, intracellular adhesion molecule-1, vascular cell adhesion molecule-1 and E-selectin were measured by standard enzyme-linked immunosorbent assays. Body composition, blood pressure, fasting blood lipids, glucose and insulin also were assessed. There were no significant changes in blood pressure, fasting blood lipids, glucose or insulin levels in either group after 1 year. There was also no change in body mass or fat mass in either group; however, there was a significant increase in lean body mass (P<0.05) in the RT group. Both CRP (P<0.01) and adiponectin (P<0.01) demonstrated significant improvements in the RT group, with no change in IL-6. Conversely, there were no associated changes in the biomarkers of cell adhesion in either group. CONCLUSIONS: This study demonstrates that moderate-intensity RT significantly results in modest improvements of inflammatory markers without affecting cell adhesion molecules in overweight women.

A preliminary study on T-786C endothelial nitric oxide synthase gene and renal hemodynamic and blood pressure responses to dietary sodium.

The purpose of the present study was to examine the role of the T-786C endothelial nitric oxide synthase (eNOS) gene polymorphism on changes in renal hemodynamics and blood pressure due to Na(+) loading. Twenty-eight older (63+/-1 years), moderately obese (39+/-2 % fat) hypertensives had their glomerular filtration rate (GFR), renal plasma flow (RPF), blood pressure (BP) and plasma nitric oxide (NO(x)) levels determined after eight days of low (20 mEq) and high (200 mEq) Na(+) diets. The two Na(+) diets were separated by a 1-week washout period. Subjects were genotyped for the eNOS-786 site and were grouped on whether they were homozygous or heterozygous for the C allele (TC+CC, n=13) or only homozygous for the T allele (TT, n=15). The TC+CC genotype group had a significantly greater increase in diastolic (P=0.021) and mean arterial (P=0.018) BP and a significant decline in both RPF (P=0.007) and GFR (P=0.029) compared to the TT genotype group with Na(+) loading. Furthermore, Na(+) loading resulted in a significant (P=0.036) increase in plasma NO(x) in the TT, but not in the TC+CC genotype group as well as a trend (P=0.051) for an increase in urine NO(x) in TC+CC, but not in the TT genotype group. The increase in BP during Na(+) loading in older hypertensives was associated with the eNOS genotype and may be related to changes in renal hemodynamics due to changes in NO metabolism.

Effect of aerobic exercise training on blood pressure sensitivity to dietary sodium in older hypertensives.

Although aerobic exercise training has been shown to lower blood pressure (BP) in older adults, its effect on BP sensitivity to dietary sodium (Na(+)) is unknown. Therefore, the present study was undertaken to examine the effect of aerobic exercise training on BP sensitivity to dietary Na(+) in older hypertensive individuals. Blood pressure was measured after 8 days of low (20 mEq) and high (200 mEq) Na(+) diets in 31 older (63+/-7 years, mean+/-standard deviation), hypertensive (152+/-11/88+/-5 mm Hg) individuals at baseline and following 6 months of aerobic exercise training (at 75% VO(2)max, 3 times/week, 40 min/session). Subjects were grouped on the basis of the difference in mean arterial BP (MAP) between diets (Na(+) sensitive: >or=5 mm Hg increase in MAP on high Na(+), n=20; Na(+) resistant: <5 mm Hg increase in MAP on the high Na(+) diet, n=11). Following 6 months of aerobic exercise training, there was a significant increase in maximal aerobic capacity (VO(2)max: 18.3+/-3.8 vs 20.7+/-4.2 ml/kg/min, P<0.017). Aerobic exercise training had a significant (P=0.02) effect on Na(+) sensitivity status, with the proportion of Na(+)-resistant individuals increasing from 35% at baseline to 61% following the 6-month aerobic exercise training programme. This study demonstrates the importance of physical activity on BP sensitivity to dietary Na(+).

Role of angiotensin converting enzyme genotype in sodium sensitivity in older hypertensives.

BACKGROUND: Individuals differ in their blood pressure (BP) response to changes in dietary sodium (Na+) intake. It is possible that differences in BP responses to dietary Na+ are influenced by genes. METHODS: A total of 35 older (62.9 +/- 1.2 years) hypertensive subjects had their mean arterial blood pressure (MABP) determined after 8 days of low (20 mmol/day) and high (200 mmol/day) Na+ intake. The insertion/ deletion polymorphism of the angiotensin converting enzyme (ACE) gene was genotyped with standard polymerase chain reaction methods. RESULTS: Of the 35 subjects, 24 were classified as sodium-sensitive (> or = 5 mm Hg increase in MABP in response to the increase in dietary Na+) and 11 were classified as sodium-resistant (<5 mm Hg increase in MABP). Those homozygous for the insertion allele of the ACE gene (insertion/insertion [II]; n = 8) had lower (P = .04) MABP responses to the increase in dietary Na+ (0 +/- 3 mm Hg) compared to heterozygotes (insertion/deletion [ID]; n = 20) (9 +/- 2 mm Hg; P = .0001) and those homozygous for the deletion allele (deletion/deletion [DD]; n = 7) (9 +/- 3 mm Hg; P = .05). The prevalence of sodium sensitivity was higher (P = .0083) in DD (71%) and ID (83%) compared to II (25%) genotype groups. CONCLUSIONS: Based on these data in older hypertensive individuals, we conclude that the ACE gene ID and DD genotypes are associated with an increase in BP during a high Na+ diet, which is consistent with the phenotypic characteristic of sodium sensitivity.

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.

Sodium-sensitive hypertension is not associated with higher sympathetic nervous system activity in older hypertensive humans.

The majority of older hypertensive humans are sodium sensitive and they are characterized by increased alpha-adrenergic responsiveness relative to their level of sympathetic nervous system (SNS) activity. To test the hypothesis that heightened SNS activity and/or increased alpha-adrenergic receptor responsiveness during sodium loading may play a role in the sodium-dependent increase in blood pressure in older sodium-sensitive hypertensives, we used compartmental analysis of [3H]norepinephrine (NE) kinetics to determine the release rate of NE into an extravascular compartment (NE2) as an index of systemic SNS activity and determined forearm blood flow responses to graded intrabrachial artery NE and angiotensin II (ANG II) infusions and platelet membrane alpha2-receptor properties in 24 older (age 64 +/- 7 years) hypertensive subjects. Subjects were studied at the end of 1 week of a low (20 mmol/day)- and again at the end of 1 week of a high (200 mmol/day)-sodium diet. Subjects were categorized as sodium sensitive (SS) if they had a > or = 5 mm Hg increase in mean arterial blood pressure (MABP) with dietary sodium loading (n = 16), or sodium-resistant (SR) if their MABP increased by < 5 mm Hg (n = 8). Neither dietary sodium intake nor sodium-sensitivity status significantly affected arterial plasma NE levels, NE2, or other NE kinetic parameters. Forearm blood flow responses to NE or to ANG II, and platelet alpha2-receptor properties were similar between the SS and SR groups. These results suggest that the sodium-dependent increase in MABP that characterizes SS hypertension among older humans is not because of an increase in systemic SNS activity or increased arterial adrenergic receptor responsiveness.

Chemical versus dual energy x-ray absorptiometry for detecting age-associated body compositional changes in male rats.

Aging is associated with increases in body mass and fat mass (FM), whereas fat-free mass (FFM) either decreases or remains unchanged. The purpose of this study was to determine whether dual-energy X-ray absorptiometry (DXA) accurately detects age-associated changes in male Fischer 344 x Brown-Norway rats ages 8, 18, and 28 months. Eviscerated animal carcasses were first examined via the Lunar DPX-IQ DXA (small animal software version 1.0; HiRes (0.6 x 1.2 mm) medium mode). Eviscerated carcasses were then weighed, autoclaved, homogenized, and fat isolated from aliquots of homogenate via methanol/chloroform extraction. In both chemical (CHEM) and DXA analysis, carcass mass (CM), FM, and % fat were significantly higher (P < 0.0001) in the 18 and 28 versus 8-month-old rats. CHEM showed greater FFM in the 18 versus 8 months-old rats but not the 28 months-old animals. DXA was unable to detect the age-associated changes in FFM. Regression analysis showed a strong correlation between CHEM and DXA methods for CM (r = 0.98, P < 0.0001) and FM (r = 0.97, P < 0.0001), but less strong for FFM (r = 0.59, P = 0.0002). In conclusion, compared to CHEM, DXA consistently overestimated CM and FM across the age groups by 9% and 77%, respectively, and underestimated FFM by 5%.

Nitric oxide biomarkers increase during exercise-induced vasodilation in the forearm.

The purpose of the study was to determine if exercise-induced vasodilation was associated with an increase in forearm plasma levels of nitric oxide (NO) biomarkers (NO2- + NO3- and L-citrulline). Twelve healthy subjects (27+/-6 yrs) performed incremental rhythmic forearm exercise with the nondominant hand for 6 min each at 15, 30 and 45% of maximal voluntary contraction (MVC). Forearm blood flow (FBF) was determined in the exercise arm using venous occlusion plethysmography. Blood samples were obtained from the antecubital vein of the exercise and nonexercise arms for the measurement of NO biomarkers. In the exercise arm, FBF increased by a mean of 150%, 335% and 585% above baseline at 15, 30 and 45% of MVC, respectively. (ANOVA, P= 0.0001). Venous plasma NO2- + NO3- levels increased from 24+/-4 micromol/L at baseline, to 29+/-5, 32+/-4 and 3+/-4 micromol/L (ANOVA, P = 0.0001). Venous plasma L-citrulline levels increased from 31+/-5 micromol/L at baseline to 58+/-10, 87+/-7 and 141+/-15 micromol/L (ANOVA, P = 0.0001). There was a linear relationship between FBF and venous plasma NO2- + NO3- (slope= 0.38+/-0.10, P=0.0007) and between L-citrulline, (slope= 5.1 +/-1.3, P = 0.0004). Venous plasma levels of NO2- + NO3- and L-citrulline in the nonexercise arm were unchanged. These results demonstrate that exercise-induced vasodilation in the forearm is associated with forearm plasma levels of NO2- + NO3- and L-citrulline, in vivo markers of NO production.

Ambulatory blood pressure after acute exercise in older men with essential hypertension.

We sought to determine whether reductions in blood pressure in hypertensives after acute exercise persist for more than the 2 to 3 h found in controlled laboratory settings. Subjects (n = 11) were obese (32 +/- 4% body fat), sedentary (VO2max 27 +/- 4 mL/kg/min) 60 +/- 6-year-old men with stage 1 or 2 essential hypertension. Ambulatory blood pressure was recorded on 1 day preceded by 45 min of 70% VO2max treadmill exercise and on another day not preceded by exercise. Systolic blood pressure was lower by 6 to 13 mm Hg for the first 16 h after exercise (P < .05) compared to the day without prior exercise. Twenty-four-hour, day, and night average systolic blood pressures were significantly lower on the day after exercise. There was a trend for peak systolic blood pressure to be lower during the entire 24 h and the day portion of the recording; peak systolic blood pressure was significantly lower during the night portion of the recording after exercise. Systolic blood pressure load (percent of systolic blood pressure readings >140 mm Hg) was reduced during the entire 24 h and the day portion of the recording after exercise. Diastolic blood pressure was lower for 12 of the first 16 h after acute exercise (hours 0 to 4, 5 to 8, 13 to 16) (P < .05) compared to the day without prior exercise. Twenty-four-hour, day, and night average diastolic blood pressure was also significantly lower on the recording after exercise. Peak diastolic blood pressure was lower over the entire 24-h period. Diastolic blood pressure load (percent of diastolic blood pressure readings >90 mm Hg) was lower during the entire 24 h and the day portion of the day after exercise. Preliminary data also suggest that common genetic polymorphisms at the angiotensinogen, lipoprotein lipase, and angiotensin converting enzyme loci may affect the blood pressure-lowering response after acute exercise. Thus, in sedentary, obese hypertensive men a single aerobic exercise session reduced blood pressure enough to result in significantly lower 24-h average systolic, diastolic, and mean arterial blood pressure. This could result in a reduced cardiovascular load during the 24 h after acute exercise in older hypertensive men.

Apolipoprotein E genotype and exercise training-induced increases in plasma high-density lipoprotein (HDL)- and HDL2-cholesterol levels in overweight men.

We determined if the apolipoprotein E (APO E) genotype affects the exercise training-induced increase in plasma high-density lipoprotein cholesterol (HDL-C) and HDL2-C. Sedentary overweight men on an American Heart Association (AHA) step I diet had plasma lipoprotein-lipids measured before and after 9 months of endurance exercise training. APO E2 (n = 6), E3 (n = 33), and E4 (n = 12) groups were similar at baseline in terms of age, body weight and composition, and plasma lipoprotein-lipid profiles. APO E2 men had a larger increase in plasma HDL-C and HDL2-C with exercise training than APO E3 and E4 men (HDL-C, 8 +/- 4 v 3 +/- 1 v 2 +/- 1 mg/dL; HDL2-C, 5 +/- 3 v 1 +/- 1 v -1 +/- 1 mg/dL; mean +/- SE, all P < .01). After adjusting for body weight changes, the increases in plasma HDL-C and HDL2-C remained greater in APO E2 versus E3 and E4 men (all P < .03). These results indicate that APO E2 men may have greater plasma HDL-C and HDL2-C increases with endurance exercise training.

Exercise training-induced blood pressure and plasma lipid improvements in hypertensives may be genotype dependent.

Exercise training improves cardiovascular disease risk, but individual responses are highly variable. We hypothesized that common polymorphic gene variations would affect these responses. Sedentary obese hypertensive older men who had undergone exercise training were typed at the apolipoprotein (apo) E, angiotensin-converting enzyme (ACE), and lipoprotein lipase (LPL) loci. Individuals of all genotype subgroups were generally similar before training; they also changed body weight, body composition, and &f1;O(2)max similarly with training. ACE insertion/insertion (II) and insertion/deletion (ID) genotype individuals (n=10) tended to reduce systolic blood pressure more with training than deletion/deletion (DD) individuals (n=8) (-10 versus -5 mm Hg, P=0. 16). ACE II and ID individuals decreased diastolic blood pressure more with training than DD individuals (-10 versus -1 mm Hg, P<0. 005). Systolic blood pressure reductions with training were also larger in apoE3 and E4 (n=15) than apoE2 men (n=3) (-10 versus 0 mm Hg, P<0.05). The same trend was evident for diastolic blood pressure (-7 versus -3 mm Hg), but the difference was not significant. Systolic (14 versus -6 mm Hg, P=0.08) and diastolic (-9 versus -5 mm Hg, P=0.10) blood pressure reductions tended to be greater in LPL PvuII +/+ (n=4) than +/- and -/- individuals (n=14). Systolic (-10 versus 3 mm Hg, P<0.05) and diastolic (-9 versus 2 mm Hg, P<0.05) blood pressure reductions were larger in LPL HindIII +/+ and +/- (n=15) than -/- persons (n=3), respectively. LPL PvuII -/- individuals (n=3) had larger increases in HDL cholesterol (11 versus 2 mg/dL, P<0.05) and HDL(2) cholesterol (8 versus 0 mg/dL, P<0.05) than LPL PvuII +/- and +/+ individuals (n=15). These results are consistent with the possibility that apoE, ACE, and LPL genotypes may identify hypertensives who will improve blood pressure, lipoprotein lipids, and cardiovascular disease risk the most with exercise training.

Improvements in blood pressure, glucose metabolism, and lipoprotein lipids after aerobic exercise plus weight loss in obese, hypertensive middle-aged men.

The clustering of metabolic abnormalities often associated with hypertension, including insulin resistance, glucose intolerance, and dyslipidemia, in middle-aged men may be the result of a decrease in cardiovascular fitness (VO2max) and the accumulation of body fat with aging. This study examines the effects of a 6-month program of aerobic exercise training plus weight loss (AEX+WL) on VO2max, body composition, blood pressure (BP), glucose and insulin responses during an oral glucose tolerance test (OGTT), glucose infusion rates (GIR) during 3-dose hyperinsulinemic-euglycemic clamps at insulin infusion rates of 120, 600, and 3,000 pmol x m(-2) x min(-1), and plasma lipoprotein levels. Compared with eight non-obese, normotensive, sedentary men (age, 62+/-2 years; 19%+/-2% fat; BP, 117+/-4/72+/-2 mm Hg), the nine obese, hypersensitive, sedentary men studied (age, 56+/-1 year; 32%+/-1% body fat; BP, 147+/-3/93+/-2 mm Hg) initially had a larger waist girth and waist-to-hip ratio (WHR) and were more hyperinsulinemic and insulin resistant with lower GIR at the two lower insulin infusion rates of the clamp and had a 2.9-fold higher EC50, the insulin concentration producing a half-maximal increase in GIR. They had higher triglyceride (TG) and lower high-density lipoprotein cholesterol (HDL-C) levels. The AEX+WL intervention reduced body weight by 9%, percent body fat by 21%, waist girth by 9%, and WHR by 3%, and increased VO2max by 16% (P < .01 for all). This was associated with decreases of 14+/-3 mm Hg in systolic and 10+/-2 mm Hg in diastolic BP, significant changes in GIR at the low (+42%) and intermediate (+39%) insulin infusion rates and EC50 (-39%) and in glucose (-21%) and insulin (-51%) responses during OGTT (P < .02 for all). AEX+WL also lowered total cholesterol by 14% and TG by 34%, and raised HDL2-C levels twofold (P < .01 for all). Thus, a 6-month AEX+WL intervention substantially lowers BP and improves glucose and lipid metabolism in obese, sedentary, hypertensive men. This suggests that hypertension and the metabolic risk factors for cardiovascular disease associated with it can be ameliorated by AEX+WL in obese, sedentary, middle-aged men.

Insulin sensitivity is associated with blood pressure response to sodium in older hypertensives.

The purpose of this study was to determine whether sodium-resistant hypertensives are more insulin resistant and whether dietary sodium restriction improves insulin sensitivity in older hypertensives. Insulin sensitivity was assessed by a frequently sampled intravenous glucose tolerance test to determine the insulin sensitivity index (SI) after 1 wk each of low- (20 mmol.l-1.day-1) and high- (200 mmol.l-1.day-1) sodium diets in 21 older (63 +/- 2 yr) hypertensives. Subjects were grouped on the difference in mean arterial blood pressure (MABP) between diets [sodium sensitive (SS): > or = 5-mmHg increase in MABP on the high-sodium diet (n = 14); sodium resistant (SR): < 5-mmHg increase in MABP on the high-sodium diet (n = 7)]. There was no dietary sodium effect on fasting plasma insulin or SI. An analysis of variance indicated a significant (P = 0.0002) group effect, with SS individuals having lower fasting plasma insulins on the low- (13 +/- 2 vs. 27 +/- 3 microU/ml) and high- (12 +/- 2 vs. 22 +/- 3 microU/ml) sodium diets compared with SR individuals. Similarly, there was a significant (P = 0.0002) group effect in regard to SI, with SS individuals having significantly higher SI on the low- (3.26 +/- 0.60 vs. 0.91 +/- 0.31 microU x 10(-4).min-1.ml-1) and high- (3.45 +/- 0.51 vs. 1.01 +/- 0.30 microU x 10(-4).min-1.ml-1) sodium diets compared with SR individuals. We conclude that SR individuals exhibit a greater degree of insulin resistance than SS individuals and that dietary sodium restriction fails to improve insulin sensitivity regardless of sodium sensitivity status.

The independent and combined effects of weight loss and aerobic exercise on blood pressure and oral glucose tolerance in older men.

The independent and combined effects of aerobic exercise training (AEX) and weight loss (WL) on blood pressure (BP) and oral glucose tolerance were studied in 97 nondiabetic, sedentary, older men. The men were assigned to either a WL (n = 31), AEX (n = 35), AEX+WL (n = 20) intervention, or to a control (CON) group (n = 11). The AEX regimen consisted of 3 days/week for 9 months, whereas WL consisted of a behavioral modification weight loss program that met weekly for 9 months. Maximal oxygen uptake increased significantly (P < .05) in both the AEX and AEX+WL groups (delta change: 0.45 +/- 0.06 and 0.43 +/- 0.07 L/min, respectively; mean +/- SEM), but did not change in the WL (delta change: 0.00 +/- 0.04 L/min) and CON (-0.05 +/- 0.07 L/min) groups. The AEX+WL and WL groups had comparable reductions in body weight (-8.6 +/- 0.7 and -8.8 +/- 0.7 kg,) and %fat (-5.4 +/- 0.5 and -5.2 +/- 0.6%) that were significantly greater than the CON and AEX groups, in which neither body weight nor %fat changed. The AEX, WL, and AEX+WL groups had significant reductions in both systolic (-6.4 +/- 1.3, -9.2 +/- 1.6, and -9.7 +/- 2.2 mm Hg, respectively) and diastolic (-5.2 +/- 1.0, -6.2 +/- 1.3, and -7.2 +/- 1.5 mm Hg, respectively) BP after their respective interventions compared with the change in systolic (3.2 +/- 3.6 mm Hg) and diastolic (-0.5 +/- 1.9 mm Hg) BP in the CON group. The AEX, WL, and AEX+WL groups also had significant reductions in glucose and insulin responses to an oral glucose tolerance test compared with the CON group. The reduction in the insulin area in the AEX+WL group was significantly greater than in the AEX and WL groups. The results of this study demonstrate that AEX and WL are effective nonpharmacologic therapies to lower BP and alter glucose and insulin responses to an oral glucose challenge. However, combining the two interventions does not result in any further improvement in BP.

Effect of dietary sodium on insulin sensitivity in older, obese, sedentary hypertensives.

Increased dietary sodium intake has been associated with an increase in blood pressure as well as a decrease in insulin-mediated glucose disposal in young healthy adults. The purpose of this study was to determine whether dietary sodium intake is associated with changes in oral glucose tolerance, insulin sensitivity, and blood pressure in older, sedentary, overweight hypertensives. Eight older (70.0 +/- 1.4 years, mean +/- SEM), overweight (40.2 +/- 3.1% body fat), mildly hypertensive (151 +/- 8/82 +/- 2 mm Hg) patients with a fasting plasma glucose < 7.8 mmol/L were studied after 2 weeks on low (3 g/day) and 2 weeks on high (10 g/day) sodium diets. To examine carbohydrate metabolism we performed a 2 h oral glucose tolerance test and a two-dose (240 and 600 pmol/m2/min) hyperinsulinemic-euglycemic clamp at the end of each sodium diet. High sodium intake was associated with a significantly greater urinary sodium excretion (364 +/- 45 mmol/day v 112 +/- 21 mmol/day; P < .0001). The increase in dietary sodium from low to high did not result in significant differences in fasting plasma glucose (6.0 +/- 0.2 v 5.8 +/- 0.1 mmol/L, P = .20) or insulin (72.5 +/- 7.8 v 69.9 +/- 12.4 pmol/L, P = 0.71) levels or in the glucose (374.0 +/- 50.8 v 493.2 +/- 45.0 mmol/min/L, P = .12) and insulin (43,783 +/- 10,278 v 44,110 +/- 12,392 pmol/min/L, P = .96) areas determined during the oral glucose tolerance test. Similarly, there was no effect of dietary sodium on insulin-mediated glucose disposal at low (5.87 +/- 1.02 v 5.60 +/- 0.94 mg/kgLBM/min, P = .36) or high (12.15 +/- 1.49 v 11.91 +/- 1.49 mg/kgLBM/min, P = .64) insulin infusion rates. Our findings suggest that, in insulin resistant hypertensives, increased dietary sodium does not affect either glucose or insulin responses during an oral glucose tolerance test or glucose disposal during a hyperinsulinemic euglycemic clamp.

Fibrinolytic responses to acute physical activity in older hypertensive men.

We tested the hypothesis that the fibrinolytic response to acute physical activity is impaired in sedentary older hypertensive men, which may contribute to the risk of exertion-triggered acute myocardial infarction in this population. Tissue-type plasminogen activator (t-PA) antigen and activity and plasminogen activator inhibitor-1 (PAI-1) antigen and activity were measured in 12 hypertensive (69 +/- 1 yr) and 11 normotensive (64 +/- 1 yr) men before and after an acute bout of submaximal exercise. Contrary to our hypothesis, there were no differences between the two groups in the fibrinolytic response to exercise. t-PA antigen and activity were significantly elevated in both the hypertensive (38 and 172%, respectively) and normotensive (45 and 130%, respectively) groups immediately after exercise but they returned to resting levels within 30 min. There was no change in PAI-1 antigen levels immediately after exercise in either group; however, PAI-1 antigen was significantly lower at 30 and 60 min postexercise in both the hypertensive (31 and 16%, respectively) and normotensive (35 and 20%, respectively) groups. PAI-1 activity was significantly lower immediately after exercise in both the hypertensive (25%) and normotensive (22%) groups and remained lower than preexercise levels at 30 min (23 and 26%, respectively) and 60 min (16 and 12%, respectively) postexercise in both groups. The results of this study demonstrate that the fibrinolytic response to an acute bout of moderate physical activity is not impaired in sedentary older hypertensive men.