Influence of fat-free mass and functional status on resting energy expenditure in underweight elders

BACKGROUND: In underweight elders, resting energy expenditure (REE) and its relationship with fat-free mass (FFM) could be modified by sarcopenia, physical activity, and functional limitation. The aims of this study were to investigate REE and its relationship with quantity and metabolic activity of FFM and to evaluate the influence of functional status on REE in underweight elderly subjects. METHODS: Forty-eight underweight elders (BMI < 20) and 54 normal weight elderly subjects (BMI 20-30) as a control group were selected. Body composition was determined by dual energy x-ray absorptiometry (DEXA). REE was measured by indirect calorimetry. Ability in activities of daily living (ADLs) was assessed by the Katz index. RESULTS: Underweight elders had significantly lower FFM, FFM index (FFM/height(2)), and REE than healthy subjects. REE adjusted for FFM with analysis of covariance remained significantly lower in the underweight group (1287 +/- 85 vs 1715 +/- 139 kcal/day in men, and 1124 +/- 63 vs 1366 +/- 91 kcal/day in women). Katz index in the underweight group was inversely correlated with REE (r = -0.68; p <.001) even after removal of FFM, FM, and gender, by multiple regression analysis. In this model, FFM and Katz index together explained approximately 54% of REE variability. CONCLUSIONS: Underweight elderly subjects show a hypometabolism due to a reduction of both FFM quantity and its metabolic activity. Functional status in ADLs comes out as an important predictor of REE independently from FFM. The limited physical activity might be the underlying determinant of this hypometabolism, but further investigations are necessary to confirm this issue.     

Resting energy expenditure and body composition in bedridden institutionalized elderly women with advanced-stage pressure sores

BACKGROUND: Our study investigated nutritional status, body composition, and resting energy expenditure (REE) in elderly patients with advanced-stage pressure sores (PS), in addition to researching any hypermetabolic condition and its relationship with PS size. METHODS: The study involved 52 institutionalized bedridden elderly women (aged 83.7 +/- 6.3 years), divided into two groups: 23 with advanced-stage (stage 3 and 4) PS and 29 without PS. Albumin, prealbumin, and retinol-binding protein were measured in all patients, and fat-free mass (FFM) and fat mass (FM) were obtained by dual-energy x-ray absorptiometry (DEXA). REE was measured by indirect calorimetry and predicted with the Harris-Benedict formula. PS area and volume were also measured. RESULTS: The elderly women with and without PS were comparable in age, FFM, and FM. Mean albumin, prealbumin, and retinol-binding protein values were lower in cases with PS. Unadjusted mean REE was significantly higher in patients with PS (1212.3 +/- 236.7 vs 1085.5 +/- 161.3 kcal/d; p <.05), even after adjusting for FFM or expressed per kilogram of body weight (25.8 +/- 6.7 vs 21.1 +/- 4.0 kcal/d/kg; p <.01). Hypermetabolism, i.e., a measured REE > 110% of the predicted REE, was seen in 74% of patients with PS and 38% of controls. The difference between measured and predicted REE (DeltaREE) correlated with PS volume (r = 0.58; p <.01), but not with area. CONCLUSION: Advanced-stage PS in elderly women are associated with a hypermetabolic state that is influenced by the volume of the PS.     

The effect of sibutramine on resting energy expenditure and adrenaline-induced thermogenesis in obese females

BACKGROUND: Sibutramine, an inhibitor of serotonin and noradrenaline uptake, reduces appetite to cause weight loss. This study tested the hypothesis that an increase in energy expenditure also contributes to this weight loss. In addition, the effects of sibutramine on adrenaline induced changes in heart rate and cardiac output were determined METHODS: Nineteen obese females randomly received either sibutramine 15 mg daily or placebo for 12 weeks along with dietary advice. Resting energy expenditure (REE) was measured and then energy expenditure was measured during a 30 min infusion of adrenaline (25 ng/min/kg IBW). Cardiac output and heart rate, measured by Duplex Colour Doppler ultrasonography, were similarly measured in the basal state and post adrenaline. All measurements were recorded at baseline and then after 12 weeks. RESULTS: Ten patients who received sibutramine reduced their weight by 8.1+/-3.8% while 9 placebo treated subjects reduced their weight by 5.1+/-4.4%, P=0.13. In absolute terms, REE decreased in placebo subjects from 1500+/-201 kcal/24 h to 1357+/-231 kcal/24 h (9.4+/-9.9%) and in sibutramine subjects from 1540+/-184 kcal/24 h to 1444+/-128 kcal/24 h (5.3+/-12.0%), P=0.77. The increased weight loss in the sibutramine group was associated with an increase in the FFM adjusted REE (2.2+/-16.1%) unlike the expected decrease (5.8+/-9.5%) in the placebo group (P=0.11). There was some suggestion (P=0.09) that the usual positive correlation between loss of weight and decline in REE was lost in the sibutramine group (r=-0.30) compared with placebo (r=0.35). There was a negative correlation between loss of FFM and decline in REE/kg FFM and (P=0.029) which was not evident in placebo (P=0.83). Adrenaline induced energy expenditure was similar in the two groups at the end of the 12 week period and there were no significant cardiovascular changes between the two groups. CONCLUSIONS: Sibutramine limits the decline in REE associated with weight loss, equivalent to about 100 kcal/d. This could allow greater numbers of people to maintain a greater degree of weight loss.     

Blockade of tumour necrosis factor-alpha in rheumatoid arthritis: effects on components of rheumatoid cachexia

OBJECTIVES: Rheumatoid arthritis (RA) is accompanied by increased resting energy expenditure (REE) and decreased fat-free mass (FFM). This is referred to as rheumatoid cachexia and is attributed to high levels of tumour necrosis factor-alpha (TNF-alpha). This study aimed to investigate the effects of anti-TNF-alpha therapy on REE, body composition, physical activity and protein intake in RA patients. METHODS: Twenty RA patients [50% female; age: (mean +/- s.d.) 61.1 +/- 6.8 yrs; body mass index (BMI): 28.3 +/- 3.7 kg/m2] and 12 age-sex-BMI-matched healthy controls were assessed. REE (indirect calorimetry), body composition (bioelectrical impedance), the International Physical Activity Questionnaire (IPAQ), diet, Health Assessment Questionnaire (HAQ), disease activity [disease activity score 28 (DAS28), erythrocyte sedimentation rate (ESR), C-reactive protein] and serum TNF-alpha were measured before (Baseline) as well as 2 weeks (Time-1) and 12 weeks (Time-2) after initiation of anti-TNF-alpha treatment. Controls were only assessed at Baseline. RESULTS: RA patients had significantly higher REE than controls at Baseline (1799.4 +/- 292.0 vs 1502.9 +/- 114.5 kcal/day, P = 0.002). Within the RA group, REE increased significantly between Time-1 and Time-2 (P = 0.001) but not between Baseline and Time-2. Sustained significant increases were observed in IPAQ (P = 0.001) and protein intake (P = 0.001). There were no significant changes in FFM or body fat. ESR (P = 0.002), DAS28 (P < 0.001), HAQ (P < 0.001) and TNF-alpha (P = 0.024) improved significantly. Physical activity (P = 0.001) and protein intake (P = 0.024) were significant between-subject factors for the elevation of REE. CONCLUSIONS: After 12 weeks of anti-TNF-alpha therapy, there were significant improvements in disease activity and physical function, as well as physical activity and protein intake, but no significant changes in REE or FFM. There is a need for longer-term studies in this field.     

Long-term effects of consumption of a novel fat emulsion in relation to body-weight management

OBJECTIVE: To assess weight maintenance after weight loss by consumption of yoghurt with a novel fat emulsion (Olibra) including effects on body composition, resting energy expenditure (REE), fat oxidation, hunger feelings and satiety hormones. DESIGN: A randomized, placebo-controlled, double-blind, parallel design. A 6-week weight loss period (2.1 MJ/day) was followed by 18 weeks weight maintenance with test (Olibra) or placebo yoghurt. SUBJECTS: Fifty overweight women (age: 18-58 years, body mass index (BMI) 25-32 kg/m2). MEASUREMENTS: In weeks 1, 7 and 25, a satiety test with questionnaires and blood samples for analysis of satiety hormones. In weeks 2, 8 and 26, REE, body weight and body composition. RESULTS: During weight maintenance after significant body weight reduction, there was no significant increase in body weight in the test group (1.1+/-3.4 kg); the placebo group did gain weight (3.0+/-3.1 kg, P<0.001). Compared to the placebo group, the test group was less hungry 4 h after yoghurt consumption in week 25 (P<0.05) and showed increased glucagon like peptide-1 values 180 min after yoghurt consumption (week 25 vs week 1, P<0.05). Measured REE as a function of fat-free mass (FFM) was significantly higher than predicted REE (P<0.05) in week 26 for the test group, but not for the placebo group. Fat mass (FM) was significantly more decreased in the test group (6.5+/-4.1 kg) compared to the placebo group (4.1+/-3.6 kg) (week 26 vs week 2, P<0.05). CONCLUSION: Consumption of Olibra yoghurt improved weight maintenance compared to placebo, which can be explained by the relatively higher REE as a function of FFM, relatively higher decrease in FM and the relatively lower increase in hunger.     

Body composition and resting energy expenditure in elderly male patients with chronic obstructive pulmonary disease

STUDY OBJECTIVE: Our study investigates nutritional status, resting energy expenditure (REE) and physical performance in elderly patients with stable COPD to identify any early conditions of hypermetabolism, malnutrition and sarcopenia. METHODS: Eighty-six males (40 stable COPD and 46 healthy subjects) over 65 years old were studied. All subjects underwent spirometry, blood gas analysis and a 6-min walking test (6MWT). Fat-free mass (FFM) and appendicular skeletal muscle mass (ASMM) were measured by dual energy X-ray absorptiometry (DEXA). REE was measured by indirect calorimetry. RESULTS: COPD patients had a lower FFM both expressed in kilograms and after correction for height squared. The prevalence of sarcopenia was higher for COPD subjects (38% vs 31%). REE, both in absolute values and adjusted for FFM was significantly higher in COPD patients. Hypermetabolism was found in 60% of COPD cases and 13.7% (P<0.01) of healthy subjects. No relationship was found in COPD patients between the measured/predicted REE ratio (REE(m)/REE(p)) and FEV1. In the hypermetabolic COPD subgroup, the REE(m)/REE(p) ratio correlated with 6MWT. CONCLUSIONS: Elderly patients with stable COPD develop an increased REE. This hypermetabolism seems to be independent of the severity of the pulmonary obstruction and to influence the patient's physical performance.     

Adipose tissue, hepatic, and skeletal muscle insulin sensitivity in extremely obese subjects with acanthosis nigricans

We evaluated insulin action in skeletal muscle (glucose disposal), liver (glucose production), and adipose tissue (lipolysis) in 5 extremely obese women with acanthosis nigricans (AN), who had normal oral glucose tolerance, and 5 healthy lean subjects, by using a 5-stage pancreatic clamp and stable isotopically labeled tracer infusion. Basal plasma insulin concentration was much greater in obese subjects with AN than lean subjects (54.8 +/- 4.5 vs 8.0 +/- 1.3 microU/mL, P < .001), but basal glucose and free fatty acid concentrations were similar in both groups. During stage 1 of the clamp, glucose rate of appearance (R(a)) (2.6 +/- 0.3 vs 3.7 +/- 0.3 micromol x kg FFM(-1) x min(-1), P = .02) and palmitate R(a) (2.4 +/- 0.6 vs 7.0 +/- 1.5 micromol x kg FFM(-1) x min(-1), P < .05) were greater in obese subjects with AN than lean subjects despite slightly greater plasma insulin concentration in subjects with AN (3.0 +/- 0.7 vs 1.1 +/- 0.4 microU/mL, P < .05). The area under the curve for palmitate R(a) (1867 +/- 501 vs 663 +/- 75 micromol x kg FFM(-1) x 600 min(-1), P = .03) and glucose R(a) (1920 +/- 374 vs 1032 +/- 88 micromol x kg FFM(-1) x 600 min(-1), P = .02) during the entire clamp procedure was greater in subjects with AN than lean subjects. During intermediate insulin conditions (plasma insulin, approximately 35 microU/mL), palmitate R(a) was 5-fold greater in subjects with AN than in lean subjects (2.6 +/- 1.1 vs 0.5 +/- 0.2 micromol x kg FFM(-1) x min(-1), P = .05). Maximal glucose disposal was markedly lower in obese subjects with AN than in lean subjects (13.0 +/- 0.8 vs 23.4 +/- 1.8 mg x kg FFM(-1) x min(-1), P = .01) despite greater peak plasma insulin concentration (1842 +/- 254 vs 598 +/- 38 microU/mL, P < .05). These data demonstrate obese young adults with AN have marked insulin resistance in multiple tissues. However, marked insulin hypersecretion can compensate for impaired insulin action, resulting in normal glucose and fatty acid metabolism during basal conditions.     

A neuroendocrinological approach to evidence an impairment of central cholinergic function in aging.

A hypothalamic pathogenesis for the reduced GH secretion in aging has been reported for both animal and man. To further address this issue we studied in 31 elderly normal subjects (6 males and 25 females, aged 66-90 yr) and in 22 young healthy controls (13 males and 9 females, aged 20-35 yr) the GH responses to GHRH test (GHRH29, 1 microgram/kg i.v. as a bolus at 0 min) alone and combined with pyridostigmine, a cholinesterase inhibitor (PD, 120 mg po 60 min before GHRH), or with arginine (ARG, 30 g in 100 ml infused from 0 to 30 min). Serum IGF-I levels were lower in elderly than in young subjects (mean +/- SE: 86.9 +/- 7.2 vs 288.7 +/- 22.1 micrograms/L, p < 0.01). The GHRH-induced GH increase was lower in elderly than in young subjects (p < 0.01). PD increased the GH response to GHRH in both groups (p < 0.001), but in elderly subjects this response persisted lower (p < 0.0001) than that observed in young adults. Also ARG coadministration potentiated the GHRH-induced GH release in both groups (p < 0.0001) but in this case the elderly's responses overlapped with the young's. The GH increase observed after combined administration of ARG and GHRH was higher (p < 0.0001) than that elicited by PD plus GHRH in elderly but not in young subjects. Analyzing individual GH responses, a GH peak below the limit of normality for young adults was observed in 19 (61.3%) elderly subjects after PD plus GHRH administration while ARG plus GHRH test elicited a normal GH peak in all but one.(ABSTRACT TRUNCATED AT 250 WORDS)     

Growth hormone (GH) responsiveness to combined administration of arginine and GH-releasing hormone does not vary with age in man

At present, the mechanism(s) underlying the reduced spontaneous and stimulated GH secretion in aging is still unclear. To obtain new information on this mechanism(s), the GH responses to both single and combined administration of GH-releasing hormone (GHRH; 1 microgram/kg iv) and arginine (ARG; 30 g infused over 30 min), a well known GH secretagogue probably acting via inhibition of hypothalamic somatostatin release, were studied in seven elderly normal subjects and seven young healthy subjects. Basal GH levels were similar in both groups, while insulin-like growth factor-I levels were lower in elderly subjects (76.7 +/- 9.2 vs. 258.3 +/- 29.2 micrograms/L; P = 0.01). In aged subjects GHRH induced a GH increase (area under the curve, 314.9 +/- 91.9 micrograms/L.h) which was lower (P = 0.01) than that in young subjects (709.1 +/- 114.4 micrograms/L.h). On the other hand, the ARG-induced GH increase in the elderly was not significantly different from that in young subjects (372.8 +/- 81.8 vs. 470.6 +/- 126.5 micrograms/L.h). ARG potentiated GH responsiveness to GHRH in both elderly (1787.1 +/- 226.0 micrograms/L.h; P = 0.0001 vs. GHRH alone) and young subjects (2113.0 +/- 444.3 micrograms/L.h; P = 0.001 vs. GHRH alone). The potentiating effect of ARG on the GHRH-induced GH response was greater in elderly than in young subjects (1013.0 +/- 553.5% vs. 237.9 +/- 79.1%; P = 0.0001); thus, the GH increase induced by combined administration of ARG and GHRH overlapped in two groups. In conclusion, these results show that, differently from the GHRH-induced GH increase, the somatotroph response to combined administration of ARG and GHRH does not vary with age. Our finding suggests that an increased somatostatinergic activity may underlie the reduced GH secretion in normal aging.     

Effect of chronic treatment with beta-blockers on resting energy expenditure in obese hypertensive patients during a low-calorie and physical training program

BACKGROUND AND AIM: To evaluate whether chronic treatment with beta-blockers influences resting energy expenditure (REE) and weight loss after a period of diet and physical activity in obese hypertensive patients. METHODS AND RESULTS: Seventy-eight obese hypertensive patients (24 males and 54 females) aged 53.7 +/- 11.1 years with mean BMI of 42.4 +/- 5.8 kg/m2 were enrolled. Thirty-eight patients were using beta-blockers while 40 patients who had not received beta-blockers in the past 6 months were the control group. REE was measured with indirect calorimetric method. Total body fat mass, total body fat-free mass (FFM) and total body water (W) were determined by bioelectrical impedance analysis. Patients and controls underwent a structured physical training program and a hypocaloric diet for a period of 31.6 +/- 10.6 days. Measured REE in patients taking beta-blockers was 1818 +/- 309 kcal/24 h and 1853 +/- 348 kcal/24 h in patients not taking beta-blockers; p = non significant. Weight and BMI loss were similar between the two groups and were respectively -6.43 +/- 2.62 kg and -2.42 +/- 0.91 kg/m2 in the beta-blocker group and -7.49 +/- 3.10 kg, -2.78 +/- 1.03 kg/m2 in the non beta-blocker group. Body composition was similar in the two groups. In the comparison between patients treated with selective beta 1-adrenoceptors blockers and non selective beta-blockers we found a significant difference in REE (1704 +/- 283 vs 1974 +/- 278; p = 0.012) and in weight loss (-5.6 +/- 2.4 vs -7.5 +/- 2.7; p = 0.048) at the end of study. CONCLUSIONS: Beta-blockers are not associated with a lower REE in obese subjects compared to other antihypertensive treatment. Use of non selective beta-adrenergic blockers is associated with a higher REE and weight loss compared to use of selective beta 1-adrenergic blockers. Non selective beta-blockers could be indicated among first choice drugs in hypertensive severely obese subjects without contraindications to beta-blockade.     

Spectral analysis of heart rate variability in elderly non-dipper hypertensive patients.

To assess by autoregressive model the frequency domain heart rate variability (HRV) during clinostatism and after passive orthostatic load (head-up tilt), 81 hypertensive and normotensive subjects (42 men and 39 women) were subdivided into four groups: 20 adult normotensive subjects (Group 1); 21 elderly normotensive subjects (Group 2); 20 elderly hypertensive subjects with nocturnal blood pressure (BP) falls (Group 3); and 20 elderly hypertensive subjects without nocturnal BP falls (Group 4). They were chosen to assess the influence of aging and arterial hypertension on sympathetic-parasympathetic balance. The age-related decrease observed in nearly all HRV spectral frequency components (normalised units [NUs], high frequency [HF] and low frequency [LF]) was reported in elderly patients in rest conditions. LF indexes resulted in decreases in Group 3 and these data seemed to be emphasised in Group 4. After passive tilt, spectral data were recorded as follows: 25.3+/-1.8 vs 17.8+/-2.2 HF, Group 2 vs Group 1, P<0.001; 72.5+/-0.8 vs 75.6+/-1.8 LF, P< 0.001, Group 2 vs Group 1. Both sympathetic and parasympathetic indexes were lower in Group 3 (44.6+/-1.1 vs 72.5+/-0.8 LF, P< 0.001, Group 3 vs Group 2; 9.9+/-1.8 vs 25.3+/-1.8 HF, P < 0.001, Group 3 vs Group 2) and data became clearer in Group 4 (8.5 2.1 vs 9.9+/-1.8 HF, P< 0.001; 40.4+/-1.5 vs 44.6+/-1.1 LF, Group 4 vs Group 3). The established influence of aging on autonomic nervous system activity appears to be increased by arterial hypertension due to worsening of the sympathetic-parasympathetic response to standardised stimulation. The loss of nocturnal BP declines in arterial hypertension was found to occur in association with a decrease in autonomic nervous system activity.     

Association of fatigue with an acute phase response in sarcoidosis.

The pathophysiological explanation for fatigue, one of the most common symptoms in sarcoidosis, still has to be elucidated. It was hypothesized that the presence of fatigue is associated with an acute phase response in sarcoidosis. A cross-sectional study was performed in 38 sarcoidosis patients. Resting energy expenditure (REE) was measured in the fasting state by indirect calorimetry using a ventilated hood and adjusted for fat-free mass (FFM). Patients with fatigue (n=25) also suffered more frequently from other symptoms, such as exercise intolerance (p=0.01), the need for sleep (p=0.02) and weight loss (p=0.01), compared to those without fatigue (n=13). However, no relationship was found between fatigue and serum angiotensin-converting enzyme (sACE) or lung function impairment. Patients with fatigue had higher levels of C-reactive protein (CRP) (11.4+/-6.8 microg x mL(-1), p<0.0001) and REE adjusted for FFM (33.0+/-3.7 kcal x kg FFM(-1), p<0.003) compared to those without fatigue (3.2+/-2.2 mg x mL(-1); 29.2+/-2.8 kcal x kg FF(-1)). Furthermore, REE/FFM was significantly related to CRP (r=0.54, p=0.001). This study confirms the presence of an acute phase response as indicated by metabolic derangements and a moderate increase in C-reactive protein levels in sarcoidosis, particularly in those patients with constitutional symptoms. Future studies should focus on the clinical relevance and therapeutic implications of these findings.     

Insulin sensitivity is increased and fat oxidation after a high-fat meal is reduced in normal-weight healthy men with strong familial predisposition to overweight

OBJECTIVE: To evaluate whether postprandial abnormalities of energy expenditure and/or lipid oxidation are present in healthy, normal-weight subjects with a strong family history of obesity and thus at high risk to become obese. DESIGN: Case-control study. SUBJECTS: A total of 16 young healthy men participated in the study. Eight subjects had both parents overweight (father's and mother's body mass index (BMI) >25 kg/m(2)) and eight had both parents with normal body weight (father's and mother's BMI<25 kg/m(2), respectively). The group of subjects with overweight parents was similar to that with normal-weight parents (control group) in terms of BMI (23.7+/-1.7 vs 22.7+/-1.1 kg/m(2)) (M+/-s.d.) and fat-free body mass (FFM) (60.5+/-4.9 vs 58.4+/-2.0 kg), but was slightly older than the control group (25.4+/-3.3 vs 22.7+/-2.4 y; P<0.05). MEASUREMENTS: Energy expenditure (EE) was measured by indirect calorimetry, and blood samples were taken for the evaluation of metabolic variables in the fasting state and every hour for 8 h after a standard fat-rich meal (protein 15%, carbohydrate 34%, fat 51%, 4090 kJ). RESULTS:: Fasting plasma glucose, cholesterol, HDL-cholesterol, triglyceride, free fatty acid (FFA) and leptin concentrations were similar in both groups of participants, but subjects with overweight parents has significantly lower plasma insulin concentrations (5.11+/-0.51 vs 7.07+/-1.56 microU/ml; P<0.007) and HOMA index of insulin resistance (1.1+/-0.1 vs 1.6+/-0.4; P<0.01). Postprandial plasma glucose, triglyceride, FFA and leptin concentrations were similar in the two groups, whereas insulin levels were significantly lower in the group with both parents overweight at 3, 5, 6, 7 and 8 h. Fasting and postprandial EE, and fasting lipid and carbohydrate oxidation were similar in both groups. On the contrary, postprandial carbohydrate oxidation (incremental area under curve) was significantly higher (196.25+/-94.75 vs 75.88+/-74.72 mg/kg FFM x 8 h; P<0.007) and that of lipid oxidation lower (90.93+/-80.32 vs 163.68+/-108.22 mg/kg FFM x 8 h; P<0.05) in the group of subjects with overweight parents. CONCLUSION: Normal-weight subjects with a strong family history of obesity present a reduced lipid oxidation in the postprandial period and a metabolic profile characterized by low plasma insulin levels and the HOMA index, which is compatible with increased insulin sensitivity. These metabolic characteristics may be considered as early predictors of weight gain and are probably genetically determined.     

Insulin sensitivity is increased and fat oxidation after a high-fat meal is reduced in normal-weight healthy men with strong familial predisposition to overweight

OBJECTIVE: To evaluate whether postprandial abnormalities of energy expenditure and/or lipid oxidation are present in healthy, normal-weight subjects with a strong family history of obesity and thus at high risk to become obese. DESIGN: Case-control study. SUBJECTS: A total of 16 young healthy men participated in the study. Eight subjects had both parents overweight (father's and mother's body mass index (BMI) >25 kg/m(2)) and eight had both parents with normal body weight (father's and mother's BMI<25 kg/m(2), respectively). The group of subjects with overweight parents was similar to that with normal-weight parents (control group) in terms of BMI (23.7+/-1.7 vs 22.7+/-1.1 kg/m(2)) (M+/-s.d.) and fat-free body mass (FFM) (60.5+/-4.9 vs 58.4+/-2.0 kg), but was slightly older than the control group (25.4+/-3.3 vs 22.7+/-2.4 y; P<0.05). MEASUREMENTS: Energy expenditure (EE) was measured by indirect calorimetry, and blood samples were taken for the evaluation of metabolic variables in the fasting state and every hour for 8 h after a standard fat-rich meal (protein 15%, carbohydrate 34%, fat 51%, 4090 kJ). RESULTS: Fasting plasma glucose, cholesterol, HDL-cholesterol, triglyceride, free fatty acid (FFA) and leptin concentrations were similar in both groups of participants, but subjects with overweight parents has significantly lower plasma insulin concentrations (5.11+/-0.51 vs 7.07+/-1.56 microU/ml; P<0.007) and HOMA index of insulin resistance (1.1+/-0.1 vs 1.6+/-0.4; P<0.01). Postprandial plasma glucose, triglyceride, FFA and leptin concentrations were similar in the two groups, whereas insulin levels were significantly lower in the group with both parents overweight at 3, 5, 6, 7 and 8 h. Fasting and postprandial EE, and fasting lipid and carbohydrate oxidation were similar in both groups. On the contrary, postprandial carbohydrate oxidation (incremental area under curve) was significantly higher (196.25+/-94.75 vs 75.88+/-74.72 mg/kg FFM x 8 h; P<0.007) and that of lipid oxidation lower (90.93+/-80.32 vs 163.68+/-108.22 mg/kg FFM x 8 h; P<0.05) in the group of subjects with overweight parents. CONCLUSION: Normal-weight subjects with a strong family history of obesity present a reduced lipid oxidation in the postprandial period and a metabolic profile characterized by low plasma insulin levels and the HOMA index, which is compatible with increased insulin sensitivity. These metabolic characteristics may be considered as early predictors of weight gain and are probably genetically determined.     

Lean, nondiabetic Asian Indians have decreased insulin sensitivity and insulin clearance, and raised leptin compared to Caucasians and Chinese subjects

OBJECTIVE: To study and compare the insulin sensitivity of healthy, nondiabetic Asian Indians with that of two other ethnic groups (Caucasian and Chinese) living in Singapore. DESIGN: Study of insulin sensitivity using euglycaemic hyperinsulinaemic glucose clamp. SUBJECTS: A total of 10 healthy, lean, young male subjects of each ethnic group, matched for age, body mass index (BMI) and physical activity. They all had normal glucose tolerance and had no family history of diabetes. MEASUREMENTS: Anthropometric parameters (BMI, waist-hip ratio (WHR) and percentage body fat (PBF)), fasting lipid profile and leptin concentration, insulin sensitivity index, and insulin clearance. RESULTS: Healthy lean (BMI 22.1+/-1.5 kg/m(2) (mean+/-s.d.)) Indians had significantly higher fasting serum leptin (5.1+/-2.5 vs Chinese 1.0+/-0.9 vs Caucasian 2.3+/-1.2 ng/ml; P<0.001), lower insulin sensitivity index (9.9+/-3.3 vs Chinese 14.1+/-3.5 vs Caucasian 18.8+/-9.2 mg/min kg fat-free mass/microU/ml; P<0.002), and lower insulin clearance (461.4+/-54.8 vs Chinese 621.0+/-99.3 vs Caucasian 646.9+/-49.2 ml/min m(2); P<0.001). Indians also had a higher PBF (26.5+/-5.2 vs Chinese 19.5+/-2.2 vs Caucasians 22.9+/-1.4%; P<0.001), diastolic blood pressure (P=0.036), fasting insulin (P<0.006) and fasting triglyceride (P=0.022). Stepwise regression analysis showed that ethnicity was the only significant independent determinant variable for the differences in insulin sensitivity index (P=0.008). CONCLUSION: Healthy lean nondiabetic Indians were more insulin resistant compared to other ethnic groups despite the similarity in living environment. These findings may warrant preventive health-care strategies for type II diabetes and coronary artery disease to target Indians at an earlier stage compared to other ethnic groups.     

Resting energy expenditure in chronic hepatitis C

BACKGROUND/AIMS: Hypermetabolism is considered to be of clinical interest in liver disease and in several chronic viral infections. Whether resting energy expenditure (REE) increases during chronic hepatitis C is not known. Our aims were: (a) to determine the metabolic state of patients with chronic hepatitis C, and (b) to evaluate the effects of interferon therapy on REE. METHODS: Forty-seven patients and 20 controls were studied. Sixteen patients failed to respond to interferon and 12 patients stopped the treatment during the first 2 months for various reasons. The 19 responders all received 1 year of interferon. REE (indirect calorimetry) and fat-free mass (FFM, bioelectric impedance analysis) were evaluated before (day 0) and after 90, 180, and 360 days of interferon. The virus load was evaluated in patients before treatment. RESULTS: On day 0, REE expressed as a ratio of FFM (REE/FFM) was higher in patients than in controls (129.2 +/- 14.7 vs 117.9 +/- 9.6 kJ kg FFM(-1) 24 h(-1), p<0.01), and was positively correlated with the viral load (r=0.45, p=0.01). On day 90, REE/FFM had significantly decreased in responders but it did not decrease in non-responders (p<0.01). In responders, REE/FFM on days 180 and 360 was similar to that of the controls. CONCLUSIONS: Chronic hepatitis C induces hypermetabolism that is normalized by interferon therapy in responders. The underlying mechanisms of chronic hepatitis C-induced hypermetabolism and its clinical relevance remain to be determined.     

Oxidative stress does not modulate metabolic rate or skeletal muscle sympathetic activity with primary aging in adult humans

Support of resting metabolic rate (RMR) by the beta-adrenergic receptors of the sympathetic nervous system is attenuated with age and contributes to declines in RMR. This may be mediated by an age-associated increase in oxidative stress that can suppress beta-adrenergic responsiveness and/or modulate sympathetic activity. To address these issues, RMR was determined in 12 young (23 +/- 1 yr, mean +/- SE) and 21 older (68 +/- 3 yr) adults before and during systemic infusion of ascorbic acid [bolus, 0.06 g/kg fat free mass (FFM); drip, 0.02]. Ascorbic acid increased plasma concentrations similarly in young (72 +/- 5 to 1107 +/- 114 micro mol/liter) and older (70 +/- 6 to 1022 +/- 63 micro mol/liter) adults, and reduced (P = 0.001) plasma concentrations of isoprostanes (young, -82.8 +/- 47; older, -107 +/- 29 pg/ml). Baseline RMR(FFM) was lower (5719 +/- 215 vs. 6703 +/- 328 kJ/d; P = 0.001) and muscle sympathetic nerve activity (MSNA) was greater (MSNA, 28 +/- 2 vs. 23 +/- 3 bursts/min; P < 0.05) in older compared with young. However, neither RMR(FFM) (young, +117 +/- 63; older, +163 +/- 48 kJ/d; P = 0.14) or MSNA (young, 0 +/- 2; older, -1 +/- 1 bursts/min; P = 0.71) changed in either age group during ascorbic acid infusion compared with saline control. These results indicate that increased oxidative stress: 1) is not a mechanism contributing to decreases in RMR with primary aging; and 2) does not modulate MSNA in healthy adult humans.     

Influence of adiposity in the blunted whole-body protein anabolic response to insulin with aging

BACKGROUND: Although insulin resistance of glucose is often reported with aging, that of protein metabolism is still debated. We tested if the insulin sensitivity of protein metabolism parallels that of glucose and is altered with aging. METHODS: Whole-body (13)C-leucine and (3)H-glucose kinetics were measured in the postabsorptive state and during an hyperinsulinemic, euglycemic, isoaminoacidemic clamp in 12 young men (age: 27 +/- 1 years; body mass index [BMI]: 23 +/- 1 kg/m(2)), 11 young women (age: 25 +/- 1 years; BMI: 21 +/- 1 kg/m(2)), 9 elderly men (age: 70 +/- 1 years; BMI: 26 +/- 1 kg/m(2)), and 10 elderly women (age: 69 +/- 2 years; BMI: 23 +/- 1 kg/m(2)). RESULTS: Postabsorptive leucine flux rates adjusted for fat-free mass (FFM) were not different between elderly and young participants. During the clamp, leucine flux and protein synthesis rates increased less in the elderly participants, and protein breakdown decreased equally. Thus, the net anabolic (protein balance) response to hyperinsulinemia was lower in elderly versus young participants (p =.007) and was highly correlated with the clamp glucose rate of disposal (r = 0.671, p <.001), indicating insulin resistance of protein concurrent with that of glucose. From regression analysis, FFM explained 73% of the variance in the anabolic response. Age explained an additional 3%, but was accounted for by markers of adiposity. FFM and percent body fat collectively explained 79% of the variance. CONCLUSION: Both reduction in absolute FFM and increased adiposity, intrinsic to the aging process, are associated with an altered anabolic action of insulin in stimulating protein synthesis. This alteration may contribute to the progressive muscle loss with aging.     

Gender variations of body composition, muscle strength and power output in morbid obesity

BACKGROUND: Motor capabilities are reduced in obese (OB) individuals, and this impairment may result also from quantitative variation of muscle mass due to alterations in body composition. OBJECTIVE: This study aims to evaluate the differences in body mass (BM) and composition, as well as in muscle strength (ST) and power output W(.) between OB and NW males and females, and to test the hypothesis that variations in body composition affect muscle performance in OB subjects. DESIGN AND METHODS: Body composition (determined by BIA with a two-compartment model), upper and lower limb maximum ST (evaluated with isotonic machines) and lower limb maximum anaerobic W(.) (measured with a jumping test) were studied in a group of 95 extremely OB subjects (OB: 28 males, 67 females; mean age+/-s.d.: 29.3+/-7.0 y; BMI: 41.2+/-4.4 kg/m(2)) and in a control group of 18 NW voluntary subjects (NW: eight males, 10 females; age: 30.3+/-5.3 y; BMI: 22.6+/-2.1 kg/m(2)). RESULTS: OB male and female subjects differed significantly with increases in BM being attained by a similar contribution of fat mass (FM) and fat-free mass (FFM) in male subjects, but mainly contributed by FM in female subjects. Compared with NW, both OB men and women had a greater amount of FFM (P<0.001) and, since a general linear correlation was found between ST and FFM (ST (N)=64.4 FFM (kg)-190.0, R(2)=0.612, P<0.001), they developed higher values of ST (P<0.05) than their respective NW counterparts. For the same reason, both OB and NW male subjects had higher ST (P<0.001) than their female counterparts. Correction for FFM eliminated all gender- and obesity-related ST differences. On the contrary, in spite of their higher absolute muscle strength, both OB men and women could develop absolute W(.) similar to that of NW subjects, and were notably less powerful per unit BM than NW subjects (P<0.001), women being most affected among the OB. CONCLUSIONS: Obesity-related variation in body composition differs considerably by gender, and is responsible for differences in muscle performance: the higher muscle strength observed in OB subjects (both men and women) and in male subjects (both OB and NW) is accounted for by a greater amount of FFM. Nonetheless, biomechanical limitations appear to impair muscle power development during jumping in OB individuals.     

Resting energy expenditure in Duchenne patients using home mechanical ventilation.

Nutritional status is both important and difficult to assess in patients with Duchenne muscular dystrophy (DMD), particularly in those requiring mechanical ventilation (MV). The current authors evaluated body composition (bio-impedancemetry), resting energy expenditure (REE; indirect calorimetry) and energy intake in 20 adult patients with DMD using home MV (nocturnal: n = 13; continuous: n = 7) and 12 age-matched healthy controls. The patients were smaller in height than the controls and had a lower body weight. Most of the reduction in body mass index was accounted for by a reduction in fat free mass (FFM). REE (kJ) was significantly reduced in the patients (4559+/-853 kJ x 24 h(-1) versus 7407+/-1312 kJ x 24 h(-1)), but the difference disappeared after correction for FFM. REE and FFM were correlated in both the controls and patients, but less strongly in the latter, the lower strength of the association being due to the patients using continuous MV (REE and FFM uncorrelated). The food intake of the patients was 1.2+/-0.4 greater than their REE. This study shows that patients with advanced forms of Duchenne muscular dystrophy have balanced energy intakes and resting energy expenditure.