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Whole-room indirect calorimeters have been used to study human metabolism for more than a century. These studies have contributed substantial knowledge to the assessment of nutritional needs and the regulation of energy expenditure and substrate oxidation in humans. However, comparing results from studies conducted at different sites is challenging because of a lack of consistency in reporting technical performance, study design, and results. In May 2019, an expert panel was convened to consider minimal requirements for conducting and reporting the results of human whole-room indirect calorimeter studies. We propose Room Indirect Calorimetry Operating and Reporting Standards, version 1.0 (RICORS 1.0) to provide guidance to ensure consistency and facilitate meaningful comparisons of human energy metabolism studies across publications, laboratories, and clinical sites.

Background Energy expenditure prediction equations are used to estimate energy intake based on general population measures. However, when using equations to compare with a disease cohort with known metabolic abnormalities, it is important to derive one's own equations based on measurement conditions matching the disease cohort. Objective We aimed to use newly developed prediction equations based on a healthy pediatric population to describe and predict resting energy expenditure (REE) in a cohort of pediatric patients with thyroid disorders. Methods Body composition was measured by DXA and REE was assessed by indirect calorimetry in 201 healthy participants. A prediction equation for REE was derived in 100 healthy participants using multiple linear regression and z scores were calculated. The equation was validated in 101 healthy participants. This method was applied to participants with resistance to thyroid hormone (RTH) disorders, due to mutations in either thyroid hormone receptor β or α (β: female n = 17, male n = 9; α: female n = 1, male n = 1), with deviation of REE in patients compared with the healthy population presented by the difference in z scores. Results The prediction equation for REE = 0.061 * Lean soft tissue (kg) − 0.138 * Sex (0 male, 1 female) + 2.41 (R2 = 0.816). The mean ± SD of the residuals is −0.02 ± 0.44 kJ/min. Mean ± SD REE z scores for RTHβ patients are −0.02 ± 1.26. z Scores of −1.69 and −2.05 were recorded in male (n = 1) and female ( n = 1) RTHα patients. Conclusions We have described methodology whereby differences in REE between patients with a metabolic disorder and healthy participants can be expressed as a z score. This approach also enables change in REE after a clinical intervention (e.g., thyroxine treatment of RTHα) to be monitored.

We describe a study to assess the precision of the GE Lunar iDXA and the agreement between the iDXA and GE Lunar Prodigy densitometers for the measurement of regional- and total-body bone and body composition in normal to obese healthy adults. We compare the whole-body fat mass by dual-energy X-ray absorptiometry (DXA) to measurements by a 4-component (4-C) model. Sixty-nine participants, aged 37 ± 12 yr, with a body mass index of 26.2 ± 5.1 kg/cm2, were measured once on the Prodigy and twice on the iDXA. The 4-C model estimated fat mass from body mass, total body water by deuterium dilution, body volume by air displacement plethysmography, and bone mass by DXA. Agreements between measurements made on the 2 instruments and by the 4-C model were analyzed by Bland-Altman and linear regression analyses. Where appropriate, translational cross-calibration equations were derived. Differences between DXA software versions were investigated. iDXA precision was less than 2% of the measured value for all regional- and whole-body bone and body composition measurements with the exception of arm fat mass (2.28%). We found significant differences between iDXA and Prodigy (p < 0.05) whole-body and regional bone, fat mass (FM), and lean mass, with the exception of hip bone mass, area and density, and spine area. Compared to iDXA, Prodigy overestimated FM and underestimated lean mass. However, compared to 4-C, iDXA showed a smaller bias and narrower limits of agreement than Prodigy. No significant differences between software versions in FM estimations existed. Our results demonstrate excellent iDXA precision. However, significant differences exist between the 2 GE Lunar instruments, Prodigy and iDXA measurement values. A divergence from the reference 4-C observations remains in FM estimations made by DXA even following the recent advances in technology. Further studies are particularly warranted in individuals with large FM contents.

Objective Associations between maternal glucose levels and increased fetal growth are well established and independent relationships with maternal weight, weight gain and insulin resistance are also observed. The relative roles of lipolysis and glucose production in the determination of these observations remain unclear. Design We examined, through detailed physiological studies, the relationship between maternal late gestational energy substrate production (glucose and glycerol), maternal weight and weight gain, and estimated fetal size in the third trimester. Patients Twenty-one nulliparous pregnant women, without gestational diabetes (GDM) assessed at 28 weeks with oral glucose tolerance test, were recruited. Measurements Rates of hepatic glucose production (GPR) and rates of glycerol production (reflecting lipolysis) using [13C6]-glucose and [2H5]-glycerol were measured at 34-36 weeks gestation. Respiratory quotient was assessed by indirect calorimetry and body composition by measurements of total body water (H218O) and body density (BODPOD). Fetal weight was estimated from ultrasound measures of biparietal diameter, femoral length and abdominal circumference. Results At 34-36 weeks bivariate analyses showed that GPR and lipolysis correlated with estimated fetal (r=0.71 and 0.72 respectively) as well as with maternal weight, fat mass and fat free mass, but not maternal weight gain. In multivariate analyses rates of both glucose production (r=0.43*) and lipolysis (r=0.46*) were independently associated with fetal size explaining 60% of the variance. Conclusions Both maternal rates of lipolysis and hepatic glucose production in late gestation are strongly related to estimated fetal weight. This article is protected by copyright. All rights reserved.

Obesity implies a failure of autoregulatory homeostatic responses to caloric excess. We studied the mechanisms, effectiveness, and limits of such responses in six lean (21.9 ± 1.3 kg/m2), healthy men based in a metabolic suite for 17 wk of progressive intermittent overfeeding (OF) (3 wk, baseline; 3 wk, 20% OF; 1 wk, ad libitum; 3 wk, 40% OF; 1 wk, ad libitum; 3 wk, 60% OF; 3 wk, ad libitum). Body composition was assessed by a four-compartment model using dual X-ray absorptiometry, deuterium dilution, and plethysmography. Magnetic resonance imaging assessed subcutaneous/visceral fat at abdominal level at baseline and at the end of 60% OF. Energy intake was assessed throughout, energy expenditure (EE) and substrate oxidation rates were measured repeatedly by whole body calorimetry (calEE), and free-living EE (TEE) was measured by doubly labeled water at baseline and after 60% OF. At the end of 60% OF, calEE and TEE had increased by just 11.4% ( P = 0.001) and 16.2% ( P = 0.001), respectively. Weight and body fat (fat mass) had increased by 5.98 kg (8.8%, P = 0.001) and 3.31 kg (22.6%, P = 0.01), respectively. The relative increase in visceral fat (32.6%, P = 0.02) exceeded that of subcutaneous fat (13.3%, P = 0.002) in the abdominal region. The computed energy cost of tissue accretion differed from the excess ingested by only 13.1% (using calEE) and 11.6% (using TEE), indicating an absence of effective dissipative mechanisms. We conclude that elevations in EE provide very limited autoregulatory capacity in body weight regulation, and that regulation must be dominated by hypothalamic modulation of energy intake. This result supports present conclusions from genetic studies in which all known causes of human obesity are related to defects in the regulation of appetite.

Alterations in energy balance must be accommodated by adjustments in the net storage of the major energy-yielding macronutrients: carbohydrate, protein, and fat. This study used continuous whole-body calorimetry to measure changes in energy expenditure and substrate oxidation during a 12-d imposed energy imbalance in six lean men on mixed diets (overfeeding: 16.5 MJ/d, +33%, n = 3; underfeeding: 3.5 MJ/d, -67%, n = 3). Changes in total energy expenditure (TEE) and its components were modest; TEE changed by +6.2% (overfeeding) and -10.5% (underfeeding). In consequence, body weight changed by +2.90 and -3.18 kg. Marked changes in metabolic fuel selection occurred over the course of the study. Carbohydrate intake (540 and 83 g/d for overfeeding and underfeeding, respectively) exerted direct autoregulatory feedback on carbohydrate oxidation (551 and 106 g/d at day 12 for overfeeding and underfeeding, respectively). Subjects were close to balance by day 5. Changes in protein oxidation were small and not sufficient to prevent the oxidation of body protein mass, or its accretion, in response to energy deficit or surplus. Fat oxidation (59 and 177 g/d for overfeeding and underfeeding, respectively) was not sensitive to dietary fat intake (150 and 20 g/d, for overfeeding and underfeeding, respectively), rather, its oxidation was inversely related to the oxidation of other substrates. Changes in fat balance accounted for 74.1% and 84.0% of the energy imbalance during overfeeding and underfeeding, respectively. This study shows a clear oxidative hierarchy for the macronutrients. Metabolic fuel selection is dominated by the need to maintain carbohydrate balance. This induces inappropriate counterregulatory alterations in fat oxidation during energy surplus.

BACKGROUND: The current epidemic of obesity demonstrates that mechanisms for maintaining human energy balance are readily subverted by adverse environmental conditions. The critical elements of this dysregulation are poorly understood. Most previous research into what regulates the intake side of the energy balance equation has been handicapped by the use of short-term within-day experimental tests. OBJECTIVE: We enrolled six non-obese men to a 17-week protocol involving three 21 days periods of progressive overfeeding (+20, +40 and +60%) separated by free diet periods to test for compensatory satiety. RESULTS: Responses to overfeeding differed markedly with evidence of 'compensators' and 'non-compensators', but on average, subsequent food intake was stimulated rather than suppressed after overfeeding in spite of markedly elevated body fat (+13%) and fasting leptin (+116%). DISCUSSION: The inefficient response of in-built appetite control mechanisms emphasizes the need to adopt intentional cognitive restraint in the modern environment when food is plentiful.

Acylcarnitines, fatty acid oxidation (FAO) intermediates, have been implicated in diet-induced insulin resistance and type 2 diabetes mellitus, as increased levels are found in obese insulin resistant humans. Moreover plasma acylcarnitines have been associated with clinical parameters related to glucose metabolism, such as fasting glucose levels and HbA1c. We hypothesized that plasma acylcarnitines would correlate with energy expenditure, insulin sensitivity and other clinical parameters before and during a weight loss intervention. We measured plasma acylcarnitines in 60 obese subjects before and after a 12 week weight loss intervention. These samples originated from three different interventions (diet alone (n = 20); diet and exercise (n = 21); diet and drug treatment (n = 19)). Acylcarnitine profiles were analysed in relation to clinical parameters of glucose metabolism, insulin sensitivity and energy expenditure. Conclusions were drawn from all 60 subjects together. Despite amelioration of HOMA-IR, plasma acylcarnitines levels increased during weight loss. HOMA-IR, energy expenditure and respiratory exchange ratio were not related to plasma acylcarnitines. However non-esterified fatty acids correlated strongly with several acylcarnitines at baseline and during the weight loss intervention (p < 0.001). Acylcarnitines did not correlate with clinical parameters of glucose metabolism during weight loss, questioning their role in insulin resistance and type 2 diabetes mellitus.

Objective: Lipid accumulation in skeletal muscle and the liver is strongly implicated in the development of insulin resistance and type 2 diabetes, but the mechanisms underpinning fat accrual in these sites remain incompletely understood. Accumulating evidence of muscle mitochondrial dysfunction in insulin-resistant states has fuelled the notion that primary defects in mitochondrial fat oxidation may be a contributory mechanism. The purpose of our study was to determine whether patients with congenital lipodystrophy, a disorder primarily affecting white adipose tissue, manifest impaired mitochondrial oxidative phosphorylation in skeletal muscle. Research Design and Methods: Mitochondrial oxidative phosphorylation was assessed in quadriceps muscle using P-31-magnetic resonance spectroscopy measurements of phosphocreatine recovery kinetics after a standardized exercise bout in nondiabetic patients with congenital lipodystrophy and in age-, gender-, body mass index-, and fitness-matched controls. Results: The phosphocreatine recovery rate constant (k) was significantly lower in patients with congenital lipodystrophy than in healthy controls (P < 0.001). This substantial (similar to 35%) defect in mitochondrial oxidative phosphorylation was not associated with significant changes in basal or sleeping metabolic rates. Conclusions: Muscle mitochondrial oxidative phosphorylation is impaired in patients with congenital lipodystrophy, a paradigmatic example of primary adipose tissue dysfunction. This finding suggests that changes in mitochondrial oxidative phosphorylation in skeletal muscle could, at least in some circumstances, be a secondary consequence of adipose tissue failure. These data corroborate accumulating evidence that mitochondrial dysfunction can be a consequence of insulin-resistant states rather than a primary defect. Nevertheless, impaired mitochondrial fat oxidation is likely to accelerate ectopic fat accumulation and worsen insulin resistance.

To develop statistical models for predicting weight loss and regain, we analyzed the phenotypic responses in an outpatient study of 60 obese subjects randomized to one of three 12-week interventions, diet (–600 kcal) alone, diet with exercise, and diet with sibutramine. This was followed by 12 weeks of observation. The best of the “baseline covariates” models was one that incorporated intervention group and baseline homeostasis model assessment–estimated insulin resistance (HOMAIR). It predicted week 12 weight change with R2 of 0.38 and root mean square error (√MSE) of 2.92 kg. An alternative model incorporating baseline fat mass plus change in weight and HOMAIR at week 4 improved the prediction (R2, 0.67, √MSE, 2.19 kg). We could not identify a satisfactory model to predict weight regain. We conclude that prediction of weight loss over 12 weeks is significantly improved when short-term weight change is incorporated into the model. This information could be utilized to forecast the success of a weight-loss program and to motivate and contribute to innovative designing of obesity trials. Clinical Pharmacology & Therapeutics (2012); 91 6, 1027–1034. doi:10.1038/clpt.2011.333

Mitochondrial dysfunction is associated with insulin resistance and type 2 diabetes. It has thus been suggested that primary and/or genetic abnormalities in mitochondrial function may lead to accumulation of toxic lipid species in muscle and elsewhere, impairing insulin action on glucose metabolism. Alternatively, however, defects in insulin signaling may be primary events that result in mitochondrial dysfunction, or there may be a bidirectional relationship between these phenomena. To investigate this, we examined mitochondrial function in patients with genetic defects in insulin receptor (INSR) signaling. We found that phosphocreatine recovery after exercise, a measure of skeletal muscle mitochondrial function in vivo, was significantly slowed in patients with INSR mutations compared with that in healthy age-, fitness-, and BMI-matched controls. These findings suggest that defective insulin signaling may promote mitochondrial dysfunction. Furthermore, consistent with previous studies of mouse models of mitochondrial dysfunction, basal and sleeping metabolic rates were both significantly increased in genetically insulin-resistant patients, perhaps because mitochondrial dysfunction necessitates increased nutrient oxidation in order to maintain cellular energy levels.

Resistance to thyroid hormone (RTH), a dominantly inherited disorder usually associated with mutations in thyroid hormone receptor beta (THRB), is characterized by elevated levels of circulating thyroid hormones (including thyroxine), failure of feedback suppression of thyrotropin, and variable tissue refractoriness to thyroid hormone action. Raised energy expenditure and hyperphagia are recognized features of hyperthyroidism, but the effects of comparable hyperthyroxinemia in RTH patients are unknown. Here, we show that resting energy expenditure (REE) was substantially increased in adults and children with THRB mutations. Energy intake in RTH subjects was increased by 40%, with marked hyperphagia particularly evident in children. Rates of muscle TCA cycle flux were increased by 75% in adults with RTH, whereas rates of ATP synthesis were unchanged, as determined by 13C/31P magnetic resonance spectroscopy. Mitochondrial coupling index between ATP synthesis and mitochondrial rates of oxidation (as estimated by the ratio of ATP synthesis to TCA cycle flux) was significantly decreased in RTH patients. These data demonstrate that basal mitochondrial substrate oxidation is increased and energy production in the form of ATP synthesis is decreased in the muscle of RTH patients and that resting oxidative phosphorylation is uncoupled in this disorder. Furthermore, these observations suggest that mitochondrial uncoupling in skeletal muscle is a major contributor to increased REE in patients with RTH, due to tissue selective retention of thyroid hormone receptor alpha sensitivity to elevated thyroid hormone levels.

Increased levels of IMCL (intramyocellular lipid) have been shown to be associated with reduced steady-state glucose infusion rates during a hyperinsulinaemic–euglycaemic clamp (M-value). The aim of the present study was to explore how IMCL levels relate to the insulin-mediated suppression of endogenous glucose production [hepatic S I (insulin sensitivity)] and increase in glucose disposal (peripheral S I ). In the present study, 11 healthy young adults (7 male, 4 female; aged 21–31 years) undertook, in random order, an hyperinsulinaemic–euglycaemic clamp combined with stable glucose isotope enrichment to measure peripheral and hepatic S I , a 1 H-MRS (proton-magnetic resonance spectroscopy) scan to determine IMCL levels and a DXA (dual-energy X-ray absorptiometry) scan to assess body composition. IMCL levels (range, 3.2–10.7) were associated with whole-body fat mass ( r =0.787, P =0.004), fat mass corrected for height ( r =0.822, P =0.002) and percentage of central fat mass ( r =0.694, P =0.02), but were not related to whole-body FFM (fat-free mass; r =−0.472, P =0.1). IMCL levels correlated closely with the M-value ( r =−0.727, P =0.01) and FFM-corrected peripheral S I ( r =−0.675, P =0.02), but were not related to hepatic S I adjusted for body weight ( r =0.08, P =0.8). The results of the present study suggest that IMCL accumulation may be a sensitive marker for attenuations in peripheral, but not hepatic, S I in normal populations. Given the close relationship of IMCL levels to whole-body and central abdominal fat mass, relative increases in the flux of lipids from adipose tissue to the intramyocellular compartment may be an integral part of the mechanisms underlying reductions in S I .

Context: Lipodystrophy is a heterogeneous condition characterized by an inherited or acquired deficiency in the number of adipocytes required for the storage of energy as triglycerides. Acquired lipodystrophy is frequently associated with other autoimmune disorders. One well-studied form is characterized by the selective loss of upper body fat in association with activation of the alternative complement pathway by C3 nephritic factor, low complement factor C3, and mesangiocapillary glomerulonephritis. Objective: We now describe an immunologically distinct form of acquired generalized lipodystrophy, with evidence of activation of the classical complement pathway (low C4) and autoimmune hepatitis. Patients and Research Design: Three unrelated patients with acquired lipodystrophy and low complement C4 levels are described. In vitro analysis of the complement pathway was undertaken to determine the reason for the low C4 complement levels. Biopsies were obtained from liver, bone marrow, and adipose tissue for histological analysis. Results: All three patients manifested near-total lipodystrophy, chronic hepatitis with autoimmune features, and low C4 complement levels. Additional autoimmune diseases, including severe hemolytic anemia, autoimmune thyroid disease, and polyneuropathy, were variably present. Detailed studies of complement pathways suggested constitutive classical pathway activation. Conclusions: Although the previously described syndrome, which typically results in a cephalad pattern of partial lipodystrophy, results from activation of the alternative complement pathway, this form, in which lipodystrophy is generalized, is associated with activation of the classical pathway. Future therapeutic approaches to these disorders may benefit from being tailored to their distinct immunopathogenesis.

Huntington's disease (HD) is a debilitating autosomal dominant, neurodegenerative disease with a fatal prognosis. Classical symptoms include motor disturbances, subcortical dementia and psychiatric symptoms but are not restricted to this triad. Patients often experience other problems such as weight loss, although why and when this occurs in the disease course is not known. We studied metabolism using whole body indirect calorimetry in both early stage HD patients and in the R6/2 transgenic mouse model of HD, at times before and after they displayed signs of disease. Using this combined approach we found that patients with early HD tended to be in negative energy balance for reasons not related to their movement disorder, which was paralleled in the transgenic R6/2 mice. These mice had significantly elevated total energy expenditure as they developed overt disease with weight loss due primarily to a loss of muscle bulk. This study has shown for the first time that in HD there is the development of early negative energy balance, which in turn may cause weight loss with loss of muscle bulk in particular. The reason for this is not known but may reflect a catabolic state secondary to hypothalamic pathology, as abnormalities have been reported in the hypothalamus early in the disease course.

OBJECTIVE— Pharmacological use of peroxisome proliferator–activated receptor (PPAR)δ agonists and transgenic overexpression of PPARδ in mice suggest amelioration of features of the metabolic syndrome through enhanced fat oxidation in skeletal muscle. We hypothesize a similar mechanism operates in humans. RESEARCH DESIGN AND METHODS— The PPARδ agonist (10 mg o.d. GW501516), a comparator PPARα agonist (20 μg o.d. GW590735), and placebo were given in a double-blind, randomized, three-parallel group, 2-week study to six healthy moderately overweight subjects in each group. Metabolic evaluation was made before and after treatment including liver fat quantification, fasting blood samples, a 6-h meal tolerance test with stable isotope fatty acids, skeletal muscle biopsy for gene expression, and urinary isoprostanes for global oxidative stress. RESULTS— Treatment with GW501516 showed statistically significant reductions in fasting plasma triglycerides (−30%), apolipoprotein B (−26%), LDL cholesterol (−23%), and insulin (−11%), whereas HDL cholesterol was unchanged. A 20% reduction in liver fat content (P < 0.05) and 30% reduction in urinary isoprostanes (P = 0.01) were also observed. Except for a lowering of triglycerides (−30%, P < 0.05), none of these changes were observed in response to GW590735. The relative proportion of exhaled CO2 directly originating from the fat content of the meal was increased (P < 0.05) in response to GW501516, and skeletal muscle expression of carnitine palmitoyl-transferase 1b (CPT1b) was also significantly increased. CONCLUSIONS— The PPARδ agonist GW501516 reverses multiple abnormalities associated with the metabolic syndrome without increasing oxidative stress. The effect is probably caused by increased fat oxidation in skeletal muscle.

Objective: To evaluate a novel quantitative magnetic resonance (QMR) methodology (EchoMRI-AH, Echo Medical Systems) for measurement of whole-body fat and lean mass in humans. Methods and Procedures: We have studied (i) the in vitro accuracy and precision by measuring 18 kg Canola oil with and without 9 kg water (ii) the accuracy and precision of measures of simulated fat mass changes in human subjects (n = 10) and (iii) QMR fat and lean mass measurements compared to those obtained using the established 4-compartment (4-C) model method (n = 30). Results: (i) QMR represented 18 kg of oil at 40°C as 17.1 kg fat and 1 kg lean while at 30°C 15.8 kg fat and 4.7 kg lean were reported. The s.d. of repeated estimates was 0.13 kg for fat and 0.23 kg for lean mass. Adding 9 kg of water reduced the fat estimates, increased misrepresentation of fat as lean, and degraded the precision. (ii) the simulated change in the fat mass of human volunteers was accurately represented, independently of added water. (iii) compared to the 4-C model, QMR underestimated fat and over-estimated lean mass. The extent of difference increased with body mass. The s.d. of repeated measurements increased with adiposity, from 0.25 kg (fat) and 0.51 kg (lean) with BMI 30 kg/m2. Discussion: EchoMRI-AH prototype showed shortcomings in absolute accuracy and specificity of fat mass measures, but detected simulated body composition change accurately and with precision roughly three times better than current best measures. This methodology should reduce the study duration and cohort number needed to evaluate anti-obesity interventions.

Background/Aims: Turner’s syndrome (TS) is associated with increased insulin resistance and adiposity, which might be associated with type 2 diabetes in later life. We aimed to determine whether the defect in insulin sensitivity is a primary intrinsic defect in TS or dependent on variation in body composition. Methods: Sixteen women with TS not on growth hormone replacement but receiving oestrogen replacement therapy [age (mean ± SD): 30.2 ± 8.5 years; height-corrected fat-free mass: 26.1 ± 3.1 kg/height] and a control group of 16 normal healthy women (age: 30.1 ± 8.2 years; height-corrected fat-free mass: 25.9 ± 2.4 kg/height) were studied. Fasting blood samples were obtained for measurement of glucose, insulin, IGF-I, IGFBP-1, IGFBP-3 and lipid levels. The hyperinsulinaemic euglycaemic clamp was performed to assess peripheral insulin sensitivity (M value), and the Homeostasis Model Assessment (HOMA-S) was used to estimate fasting insulin sensitivity. Body composition was assessed using a dual-energy X-ray absorptiometry scan. Results: Fasting insulin sensitivity (HOMA-S 103.2 ± 78.6 vs. 193.9 ± 93.5, p = 0.006) was lower in TS subjects compared to controls as was whole-body insulin sensitivity (M value 2.9 ± 1.9 vs. 5.5 ± 2.6 mg/kg/min, p = 0.003). In a multiple regression analysis the Turner karyotype was significantly related to insulin sensitivity (p = 0.008) independent of any differences in fat-free mass and percent whole-body fat mass. Conclusion: The increased insulin resistance in women with TS is independent of measures of body composition and may represent an intrinsic defect related to their chromosomal abnormality.

Humans respond to an acute excess of ingested energy by storing the surplus energy as triglyceride in white adipose tissue. To study the energetic response to acute overfeeding in human subjects with limited adipose tissue capacity, we recruited seven subjects with lipodystrophy and seven lean healthy controls. Total fat mass was approximately 70% lower in lipodystrophic subjects (mean, 6.1 kg) than in body mass index-matched lean controls (mean, 22.0 kg). Energy expenditure and macronutrient oxidation rates were assessed in chamber calorimeters on two separate occasions for 40 h, during which time subjects consumed either an energy-balanced diet or a diet incorporating 30% excess energy as fat. On the energy-balanced diet, total daily energy expenditure and basal metabolic rate were linearly associated with lean mass in both groups (r(2) = 0.83) and were not significantly different between groups when corrected for lean mass. In response to the fat challenge, total energy expenditure did not increase significantly in healthy controls (9,472 +/- 1,069 to 9,724 +/- 1,114 kJ/d; P = 0.189). Substrate oxidation results confirm that excess fat was predominantly stored. In contrast, lipodystrophic subjects significantly increased total daily energy expenditure (11,081 +/- 1,226 to 11,730 +/- 1,374 kJ/d; P0.005). This was largely attributable to a 29% increase in fat oxidation. Thus, subjects with lipodystrophy uniquely respond to an acute hypercaloric load with a higher energy expenditure increment and by increasing fat oxidation. Insight into the molecular mechanisms responsible for this phenomenon may yield novel therapeutic approaches for obesity.

This study compared the in vivo and in vitro performances of the Lunar MD and Prodigy dual-energy X-ray absorptiometers (DXAs). Ten volunteers and three different spine phantoms were studied to determine the effect of scan mode, tissue depth, and bone density on measures of spine bone area (BA), bone mineral content (BMC), and areal bone mineral density (BMD). These studies demonstrated that the choice of scan mode was most important for the Prodigy and for subjects who were thin, obese, or had low BMD. Increase in tissue depth caused an increase in measured BMC and BMD for the MD but had a small effect on Prodigy results if the appropriate scan mode was selected. BA was dependent on the BMD for both DXA systems. Results using a hydroxyapatite phantom demonstrated that after correcting for the calibration of Lunar systems, the BMC measured by the MD and Prodigy was similar to the calculated hydroxyapatite content of the phantom. In vivo studies confirmed the in vitro findings and demonstrated that even when the appropriate scan mode was selected, the BMC, BMD, and T-scores were significantly higher on the Prodigy than MD.

Inherited defects in signaling pathways downstream of the insulin receptor have long been suggested to contribute to human type 2 diabetes mellitus. Here we describe a mutation in the gene encoding the protein kinase AKT2/PKBβ in a family that shows autosomal dominant inheritance of severe insulin resistance and diabetes mellitus. Expression of the mutant kinase in cultured cells disrupted insulin signaling to metabolic end points and inhibited the function of coexpressed, wild-type AKT. These findings demonstrate the central importance of AKT signaling to insulin sensitivity in humans.

OBJECTIVE: To test the hypothesis that acute responses of plasma leptin concentration to energy balance manipulation are mediated by fat flux. DESIGN: Ten healthy women aged 31-63 y, mass 48-113.5 kg, fat mass 8.5-62.5 kg, were studied for 3 days in a whole-body calorimeter on two occasions. After a control day (D1) during which energy balance was maintained, diet was manipulated to induce fat deposition (FD) or mobilization (FM) of 50 g/day for 2 days (D2 and D3). A difference totalling of 194+/-18.6 g fat was achieved between manipulations without significant effects on carbohydrate or protein balance. Fasting plasma leptin was measured on D2 and D4. RESULTS: After the control day plasma leptin concentration averaged 19.01+/-9.8 ng/ml, and was found to be linearly related to body fat mass. After 2 days manipulation of fat balance, leptin concentrations were 21.4+/-10.3 ng/ml (FD) and 21.2+/-11.3 ng/ml (FM). There was no significant difference between treatments in either control day or postmanipulation leptin concentrations, nor did the treatments induce any differences in glucose or insulin concentration responses. CONCLUSION: Although in states of energy balance leptin concentration is linearly related to fat mass, acute modulation of leptin concentration during energy imbalance is not mediated by fat flux.

OBJECTIVE: To determine dose-dependent relationship between ingested fat and its oxidation in the immediate post-prandial period in humans. DESIGN: Subjects were randomly selected for the study at the Dunn Clinical Nutrition Centre, Cambridge, UK. Subjects ingested naturally enriched 13C corn-oil doses (range 20-140g) in a whole-body indirect calorimeter, and were studied for 8 h. Ingested fat oxidation was estimated from the subject's breath 13C enrichment and total carbon dioxide production. Total fat and carbohydrate oxidation were estimated from non-protein oxygen and carbon dioxide exchanges. Endogenous fat oxidation was estimated as the difference between total fat and ingested fat oxidation. RESULTS: The amount of fat dose oxidized was nonlinearly related to the amount ingested. On average, 25.6+/-2.7% of the mean fat dose was oxidized. A significant (r = - 0.72, P < 0.001) inverse correlation was found between the amount of fat dose and the proportion oxidized. Endogenous carbohydrate oxidation was negatively and significantly correlated to fat dose oxidized (r= -0.61, P < 0.01), but it was not correlated to endogenous fat oxidation. CONCLUSIONS: There was a nonlinear relationship between amount of fat dose and its quantity that was oxidized in the immediate post-prandial period. The inverse relationship between the size of the fat load and the proportion that was oxidized post-prandially implies increased dietary fat storage beyond about 50 g in a normal resting adult. This has important implications for 13CO2-based studies.

BACKGROUND: Although international interest in classifying subject health status according to adiposity is increasing, no accepted published ranges of percentage body fat currently exist. Empirically identified limits, population percentiles, and z scores have all been suggested as means of setting percentage body fat guidelines, although each has major limitations. OBJECTIVE: The aim of this study was to examine a potential new approach for developing percentage body fat ranges. The approach taken was to link healthy body mass index (BMI; in kg/m(2)) guidelines established by the National Institutes of Health and the World Health Organization with predicted percentage body fat. DESIGN: Body fat was measured in subjects from 3 ethnic groups (white, African American, and Asian) who were screened and evaluated at 3 universities [Cambridge (United Kingdom), Columbia (United States), and Jikei (Japan)] with use of reference body-composition methods [4-compartment model (4C) at 2 laboratories and dual-energy X-ray absorptiometry (DXA) at all 3 laboratories]. Percentage body fat prediction equations were developed based on BMI and other independent variables. RESULTS: A convenient sample of 1626 adults with BMIs < or =35 was evaluated. Independent percentage body fat predictor variables in multiple regression models included 1/BMI, sex, age, and ethnic group (R: values from 0.74 to 0.92 and SEEs from 2.8 to 5.4% fat). The prediction formulas were then used to prepare provisional healthy percentage body fat ranges based on published BMI limits for underweight ( or =25), and obesity (> or =30). CONCLUSION: This proposed approach and initial findings provide the groundwork and stimulus for establishing international healthy body fat ranges.

The Tanita body-fat analyser is a novel device to estimate body fat, based on the principles of bioelectrical impedance. It differs from other impedance systems which use surface electrodes in that the subjects stand bare-footed on a metal sole-plate which incorporates the electrodes, hence impedance is measured through the legs and lower trunk. In 104 men and 101 women (16–78 years and BMI 16–41 kg/m2) the mean bias in body-fat mass measured using the Tanita body-fat analyser was 0·8 (2SD 7·9) KG RELATIVE TO A FOUR-COMPARTMENT MODEL. THIS IS COMPARABLE TO THE OTHER PREDICTION TECHNIQUES TESTED (CONVENTIONAL TETRAPOLAR IMPEDANCE -1·3 (2sd 6·9) kg, skinfold thicknesses 0·3 (2sd 7·4) kg, and BMI-based formulas -0·2 (2sd 9·0) kg and -0·6 (2sd 8·5) kg), but the agreement was poorer than for ‘reference’ methods to measure body fat (density 0·2 (2sd 3·7) kg, total body water -0·9 (2sd 3·4) kg and dual-energy X-ray absorptiometry 0·1 (2sd 5·0) kg). The present paper also describes the derivation of a new prediction equation for the calculation of body composition from the Tanita body-fat analyser. The equation incorporates sex, age, and a log-transformation of height, weight and the measured impedance to predict body fat measured by a four-compartment model. This approach is recommended in the derivation of other prediction equations in body composition analysis. Using this novel prediction equation the residual standard deviations were 4·8 % for men and 3·3 % for women. A similar analysis using data collected with a conventional tetrapolar system yielded residual standard deviations of 4·3 % for men and 3·1 % for women. This demonstrates that the practical simplicity of the novel Tanita method is not associated with a clinically significant decrement in performance relative to a traditional impedance device.

Background: Studies in lean men show poor regulation of energy (EB) and fat balance (FB) during manipulation of dietary ratios of fat to carbohydrate. High-fat (HF), high-energy diets cause hyperphagia and a positive EB and FB. Objective: The protocol was designed to measure substrate flux and EB in obese women taking dexfenfluramine (DF) or placebo (PL) during an HF (50% of energy) or low-fat (25% of energy; LF) diet. We hypothesized that alterations in dietary fat would not be regulated and would lead to a positive EB and FB. Design: The study was double-blind, randomized, and placebo-controlled, with 4 treatments (LF/DF, HF/DF, LF/PL, and HF/PL) and a crossover. Five days of continuous, whole-body calorimetry measurements were made in 6 subjects after 8 d of home DF/PL treatment. Macronutrient balance and EB were measured within the chamber as the cumulative difference between ad libitum intake and oxidation. Results: The HF diet increased energy (HF, 10.50 MJ/d; LF, 8.13 MJ/d; P< 0.0001) and fat intakes (HF, 5.34 MJ/d; LF, 2.06 MJ/d; P< 0.0001), leading to a positive EB (A = 2.37 MJ/d) and FB (A = 2.31 MJ/d). DF reduced energy (DF, 8.96 MJ/d; PL, 9.66 MJ/d; P< 0.01) and macronutrient intakes, but did not increase energy expenditure (A = -0.31 MJ/d; P< 0.01), or 24-h fat oxidation (A = 0.03 MJ/d; P = 0.46). Conclusions: EB and FB are poorly regulated with HF, energy-dense diets in obese women, which leads to fat deposition and weight gain. Am J Clin Nutr 1998;68:1012-21.

Background/objectives: The objective of this study was to develop approaches to expressing resting energy expenditure (REE) and lean body mass (LM) phenotypes of metabolic disorders in terms of Z-scores relative to their predicted healthy values. Subjects/methods: Body composition and REE were measured in 135 healthy participants. Prediction equations for LM and REE were obtained from linear regression and the range of normality by the standard deviation of residuals. Application is demonstrated in patients from three metabolic disorder groups (lipodystrophy, n=7; thyrotoxicosis, n=16; and resistance to thyroid hormone (RTH), n=46) in which altered REE and/or LM were characterised by departure from the predicted healthy values, expressed as a Z-score. Results: REE (kJ/min)=−0.010 × age (years)+0.016 × FM (kg)+0.054 × fat-free mass (kg)+1.736 (R2=0.732, RSD=0.36 kJ/min). LM (kg)=5.30 × bone mineral content (kg)+10.66 × height2 (m)+6.40 (male). LM (kg)=0.20 × fat (kg)+14.08 × height2 (m)−2.93 (female). (male R2=0.55, RSD=3.90 kg; female R2=0.59, RSD=3.85 kg). We found average Z-scores for REE and LM of 1.77 kJ/min and −0.17 kg in the RTH group, 5.82 kJ/min and −1.23 kg in the thyrotoxic group and 2.97 kJ/min and 4.20 kg in the LD group. Conclusion: This approach enables comparison of data from individuals with metabolic disorders with those of healthy individuals, describing their departure from the healthy mean by a Z-score.

Few studies have investigated the effects of infant nutrition on later bone health in term infants, although low sn-2 palmitate in infant formulas has been shown to result in the formation of stool fatty acid soaps, reduced Ca absorption and lower bone mass in the short term. To investigate the effect of (1) breast-feeding (BF) and (2) the type of infant formula (standard fat blend v. high-sn-2 fat blend) on bone mass at age 10 years, anthropometry and bone mass (from dual-energy X-ray absorptiometry (GE Lunar Prodigy); lumbar spine (LS) and total body less head; adjusted for size (bone mineral apparent density standard deviation score (SDS) and regression)) were measured in 10-year-old subjects born at term and either breast-fed (n 34) or randomised to a standard control formula (n 27) or a high-sn-2 palmitate formula (n 30) for the first 12 weeks of life. At follow-up, previously BF children were older but lighter (by 0·5 SDS, P= 0·03) than formula-fed children with a lower LS bone mineral density SDS (by 0·44, P= 0·03), but size-adjusted bone mass did not differ. There were no significant differences in bone mass between the formula-fed groups. These findings suggest that there is no significant effect of BF or high-sn-2 infant formula on size-adjusted bone mass in mid-childhood, and that the effects of infant nutrition on bone mass previously reported may be confined to the short term. A larger study would be required to exclude smaller effects.

The effect of alcohol on overnight energy expenditure and substrate disposal was studied in eleven subjects (five men, six women) using whole-body indirect calorimetry for 15·5 h after test meals. Three test meals were studied in random order with at least 48 h between treatments: control, 50% of maintenance energy needs provided as 14, 40 and 46% energy from protein, fat and carbohydrate respectively; alcohol addition, control plus 23% energy as alcohol; alcohol substitution, control with alcohol replacing 23% of carbohydrate energy. ANOVA revealed no significant sex effects. Alcoholinduced thermogenesis dissipated only 15 (SD 14)% of the alcohol energy. Alcohol addition had no significant effect on protein or carbohydrate oxidation but fat oxidation was suppressed (P < 0·0005) to an extent equivalent to storing 74 (SD 51)% of the alcohol energy as fat. Alcohol substitution reduced carbohydrate oxidation (P < 0·009) to an equivalent of 42 (SD 41)% and also spared fat (P < 0·005) to an equivalent of 59 (SD 37)% of the alcohol energy. It is concluded that alcohol has no special thermogenic capacity, and that its energy can be accounted for in a similar way to carbohydrate.

The accuracy of a variety of in vivo body-composition techniques (densitometry, total body water, skinfold thicknesses, whole-body impedance and resistance, body mass index, and two three-compartment models) was assessed by comparison with fat balance. Three subjects were overfed and three underfed while confined to a 30-m3 whole-body calorimeter continuously for 12 d. Mean weight changes were +2.90 kg during overfeeding and -3.47 kg during underfeeding. The change in fat mass accounted for 37.1% during overfeeding and 59.3% during underfeeding. In comparison with energy and nitrogen balance, a three-compartment model yielded the least bias and greatest precision. The smallest change in fat mass that can be measured by such a method in an individual subject is 1.54 kg (2 SD). Of the prediction techniques considered, skinfold thicknesses or the body-mass-index formula appear to be more precise than estimates based on resistance or impedance.

The hypothesis that carbohydrate stores are an important determinant of voluntary food intake was tested by covert dietary manipulation of carbohydrate stores in nine men during 2 d of continuous whole-body calorimetry that provided half-hourly monitoring of energy and fuel balance. On day 1 subjects were fed diets intended to maintain energy balance but containing carbohydrate at either 3% (depletion) or 47% (control) energy. Average carbohydrate balance changed by 153 +/- 42 g (mean +/- SD). Subsequent (day 2) ad libitum food intake from a normal diet of fixed macronutrient composition was identical on the control and depletion protocols: 12.73 +/- 2.24 and 12.72 +/- 2.01 MJ, respectively. The carbohydrate-depletion protocol caused a suppression of carbohydrate oxidation (174 +/- 41 vs 256 +/- 39 g, P < 0.001) and a reciprocal elevation in fat oxidation (120 +/- 11 vs 89 +/- 12 g, P < 0.001). These readjustments in fuel utilization were the primary mechanism for re-establishing carbohydrate balance. This study does not support the hypothesis that the need to maintain specific carbohydrate stores is a determinant of food intake in the short term.

Twelve women were studied before pregnancy and at 6-wk intervals from 6 to 36 wk gestation. Total energy expenditure (TEE) by the doubly labeled water method, basal metabolic rate (BMR), energy intake, and body composition were assessed on each occasion. There was substantial interindividual variation in the response to pregnancy. Mean total energy costs were as follows: delta BMR 112 +/- 104 MJ (range -53 to 273), delta TEE 243 +/- 279 MJ (range -61 to 869 MJ), and fat deposition 132 +/- 127 MJ (range -99 to 280 MJ). The mean total cost of pregnancy (cumulative TEE above baseline+energy deposited as fat and as products of conception) was 418 +/- 348 MJ (range 34-1192 MJ). This was much higher than current recommendations for incremental energy intakes. Self-recorded incremental intakes (208 +/- 272 MJ) seriously underestimated the additional costs. The variability in response emphasizes the problems in making prescriptive recommendations for individual women, because there is no way of predicting metabolic or behavioral responses to pregnancy.

Glycogen forms the smallest yet most labile energy substrate store. Therefore studying carbohydrate flux may be crucial to understanding the regulation of energy balance. Indirect calorimetry has been used to measure carbohydrate oxidation overnight and during exercise in nine fasted subjects. Overnight carbohydrate oxidation (averaging 2.85 +/- 0.8 g h-1) was assumed to be derived primarily from hepatic glycogen since subjects were inactive or asleep, and since glucose oxidized after gluconeogenesis from protein is measured as protein oxidation. Lower-limb muscle glycogen stores were depleted by repeated 30-min periods of cycle ergometry at 45% VO2max until exhaustion (8 +/- 1 periods). The carbohydrate oxidation rate decreased as exercise progressed. Quadratic curves yielded a close fit to each individual's exercise carbohydrate depletion data (mean multiple correlation r = 0.9996) and provided excellent inter-subject discrimination. Total (muscle plus liver) glycogen stores prior to exercise were estimated by extrapolation of the depletion curves to zero oxidation rate. This produced an extrapolation of the depletion curves to zero oxidation rate. This produced an estimate (174 +/- 61 g) which compared well with predictions (208 +/- 43 g) based on reference values for muscle mass and initial glycogen content. The results demonstrate that non-invasive estimates of glycogen status can be obtained from accurate respiratory exchange data.

Hydrogen is produced during fermentation in the large intestine and may be excreted in breath and flatus or further metabolized by the flora. However, there is little information about total H2 excretion from different substrates or the extent to which it is metabolized in the colon. We have therefore measured total H2 and methane excretion in 10 healthy subjects using a whole body calorimeter. Breath gases were measured simultaneously with total excretion in response to lactulose, pectin, and banana starch. Metabolic activities of the predominant H2 consuming anaerobes (methanogenic, sulfate reducing, and acetogenic bacteria) were measured in fecal samples. Total H2 excretion on a starch and fiber-free diet was 35 +/- 6.1 mL/24 h +/- SEM. H2 from 7.5 g, 15 g, and 22.5 g lactulose was 88.1 +/- 22.4 mL, 227.0 +/- 60.7 mL, and 321.8 +/- 79.2 mL. Four of the subjects also excreted CH4, which was 51.3 +/- 5.5 mL, 97.3 +/- 18.4 mL, and 157.5 +/- 36.3 mL for the respective lactulose doses. H2 excretion was less in methanogenic subjects (7.9 mL/g lactulose) than in nonmethanogenic (17.3 mL/g), but total H2 excreted as, hydrogen + methane, was 34.9 mL/g. H2 from pectin (20 g) was 14.1% +/- 3.2% and from starch (22.2 g) 38.6% +/- 9.2% of an equivalent lactulose dose. Sixty-five percent of total H2 and CH4 was expired in breath at total excretion rates up to 200 mL/24 h. Over this the proportion decreased to 25% with an overall average of 58%. Only subjects with CH4 excretion in vivo showed methanogenesis in feces, whereas nonmethanogenic subjects showed high sulfate-reducing activity in feces (58.7 +/- 5.6 nmol 35SO4 reduced.h-1.g-1 wet wt vs. 7.9 +/- 2.0 nmol.h-1.g-1 in methanogens). Acetogenesis rates were very low in both groups. It was concluded that H2 excretion varies with different substrates. The proportion of H2 that is exhaled in breath is higher than currently accepted and varies with total excretion rate. Substantial amounts of H2 are consumed by methanogenic and sulfate-reducing bacteria. (Gastroenterology 1992 Apr;102(4 Pt 1):1269-77)

We have recently reported a validation study of a prototype low-field strength quantitative magnetic resonance (QMR) instrument for measurement of human body composition (EchoMRI-AH). QMR was very precise, but underreported fat mass (FM) by 2-4 kg when compared to a 4-compartment (4C) model in this cross-sectional study. Here, we report the performance of an updated instrument in two longitudinal studies where FM was decreasing. Healthy obese volunteers were given a modest energy deficit diet for 8 weeks (study A) and obese patients with heart failure and/or at high cardiovascular risk were prescribed a low energy liquid diet for 6 weeks (study B). FM was measured at the start and end of these periods by QMR, dual-energy X-ray absorptiometry (DXA) and 4C. A higher proportion of the weight lost came from fat in study A compared with study B, where loss of total body water (TBW) played a greater part. The intraclass correlation between QMR and 4C estimates of FM loss (DeltaFat) was 0.95, but 20 of 22 estimates of DeltaFat by QMR were lower than the corresponding estimate by the 4C model. Bland-Altman analysis demonstrated that estimates of FM loss by QMR were ~1.0 and 0.7 kg lower than those obtained with 4C (P = 0.0008) and DXA (P = 0.049), respectively. Measurement precision remained high. QMR measurement should prove valuable for quantifying modest changes of FM in small trials.

Summary Background Reduced insulin sensitivity and increased fat mass have been reported in children and adults with congenital adrenal hyperplasia (CAH). To understand the potential mechanisms underlying these differences, we assessed insulin sensitivity and body composition in children with classical or nonclassical (late-presenting) CAH compared with normal controls. Subjects and methods Thirty-seven children with CAH (26 classical and 11 nonclassical) median (range) age 9·4 year (0·5–15·8) were compared with 41 healthy control children age 11·0 year (3·2–17·1). All children had an overnight fasting blood sample and body composition assessed by DEXA. Pubertal children (14 CAH and 19 controls) also had an oral glucose tolerance test. Classical and nonclassical CAH groups were each compared with controls, adjusting for age, gender and pubertal status. Results Classical CAH children had more fat mass than controls (P = 0·03), while nonclassical CAH children had more lean mass (P = 0·006) and higher systolic blood pressure (P = 0·003) than control children. Among pubertal children, nonclassical CAH children had higher mean insulin (0–120 min; P = 0·04), stimulated insulin (0–30 min; P = 0·02), 120 min insulin (P = 0·004) and 120 min glucose levels (P = 0·03) than controls, but no difference in disposition index. Discussion Greater body fat in classical (early-presenting) CAH children could reflect the effects of lifetime glucocorticoid therapy. In contrast, the greater lean mass and parameters of insulin resistance in nonclassical (late-presenting) CAH children likely indicate the adverse metabolic effects of prolonged postnatal androgen excess.

Metabolic dyslipidemia is characterized by high circulating triglyceride (TG) and low HDL cholesterol levels and is frequently accompanied by hepatic steatosis. Increased hepatic lipogenesis contributes to both of these problems. Because insulin fails to suppress gluconeogenesis but continues to stimulate lipogenesis in both obese and lipodystrophic insulin-resistant mice, it has been proposed that a selective postreceptor defect in hepatic insulin action is central to the pathogenesis of fatty liver and hypertriglyceridemia in these mice. Here we show that humans with generalized insulin resistance caused by either mutations in the insulin receptor gene or inhibitory antibodies specific for the insulin receptor uniformly exhibited low serum TG and normal HDL cholesterol levels. This was due at least in part to surprisingly low rates of de novo lipogenesis and was associated with low liver fat content and the production of TG-depleted VLDL cholesterol particles. In contrast, humans with a selective postreceptor defect in AKT2 manifest increased lipogenesis, elevated liver fat content, TG-enriched VLDL, hypertriglyceridemia, and low HDL cholesterol levels. People with lipodystrophy, a disorder characterized by particularly severe insulin resistance and dyslipidemia, demonstrated similar abnormalities. Collectively these data from humans with molecularly characterized forms of insulin resistance suggest that partial postreceptor hepatic insulin resistance is a key element in the development of metabolic dyslipidemia and hepatic steatosis.

Item does not contain fulltext OBJECTIVE: Untreated GH-deficient adults are predisposed to insulin resistance and excess cardiovascular mortality. We showed previously that short-term treatment with a very low GH dose (LGH) enhanced insulin sensitivity in young healthy adults. The present study was therefore designed to explore the hypothesis that LGH, in contrast to the standard GH dose titrated to normalize serum IGF-I levels (SGH), may have differing effects on insulin sensitivity, body composition, and cardiovascular risk markers [lipid profile, C-reactive protein (CRP), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha) and adiponectin] in adults with severe GH deficiency. PATIENTS AND METHODS: In this 12-month open, prospective study, 25 GH-deficient adults were randomized to receive either a fixed LGH (0.10 mg/day, n = 13) or SGH (mean dose 0.48 mg/day, n = 12), and eight age- and body mass index (BMI)-matched GH-deficient adults acted as untreated controls. Fasting blood samples were collected at baseline and at months 1, 3, 6, 9 and 12. Assessments of insulin sensitivity, using the hyperinsulinaemic euglycaemic clamp technique, and body composition, using dual-energy X-ray absorptiometry, were performed at baseline and at month 12. RESULTS: The LGH decreased fasting glucose levels (P < 0.01) and enhanced insulin sensitivity (P < 0.02), but body composition, nonesterified fatty acid (NEFA) levels and cardiovascular risk markers were unchanged. The SGH did not modify insulin sensitivity, decreased truncal fat mass (P < 0.05), CRP (P < 0.05) and IL-6 (P < 0.05) levels, and increased NEFA levels (P < 0.05). No changes were observed with the untreated controls. CONCLUSION: Our data indicate that, in contrast to the SGH, fixed administration of the LGH enhances insulin sensitivity with no apparent effects on body composition, lipolysis and other surrogate cardiovascular risk markers in adults with severe GH deficiency. Thus, the LGH may potentially be a beneficial replacement dose in reducing type 2 diabetes risk in adults with severe GH deficiency.

This study compared the in vivo and in vitro performances of the Lunar MD and Prodigy dual-energy X-ray absorptiometers (DXAs). Ten volunteers and three different spine phantoms were studied to determine the effect of scan mode, tissue depth, and bone density on measures of spine bone area (BA), bone mineral content (BMC), and areal bone mineral density (BMD). These studies demonstrated that the choice of scan mode was most important for the Prodigy and for subjects who were thin, obese, or had low BMD. Increase in tissue depth caused an increase in measured BMC and BMD for the MD but had a small effect on Prodigy results if the appropriate scan mode was selected. BA was dependent on the BMD for both DXA systems. Results using a hydroxyapatite phantom demonstrated that after correcting for the calibration of Lunar systems, the BMC measured by the MD and Prodigy was similar to the calculated hydroxyapatite content of the phantom. In vivo studies confirmed the in vitro findings and demonstrated that even when the appropriate scan mode was selected, the BMC, BMD, and T-scores were significantly higher on the Prodigy than MD.

Cats have a requirement for dietary protein two to three times that of omnivores and herbivores. This was reported to be due to the hepatic catabolic enzymes of this species being set to a permanently high level and, therefore, showing little adaptation to low dietary protein. A major mechanism for adapting to dietary protein in other species is amino acid oxidation (hereafter referred to as protein oxidation), and the objective of this study was to determine whether protein oxidation in cats was correlated with protein intake. Net protein and net fat oxidation in six adult cats were studied directly from gas exchanges using indirect calorimetry, after feeding moderate protein (MP; 35% energy) and high protein (HP; 52% energy) diets. Protein oxidation was significantly higher (P < 0.05) when cats were fed the HP diet (28.4 plus minus 0.7 mg/min) rather than the MP diet (20.4 plus minus 0.8 mg/min). Fat oxidation was significantly higher (P < 0.05) when cats consumed the MP diet (9.0 plus minus 0.7 mg/min) rather than the HP diet (4.7 plus minus 0.5 mg/min). Protein oxidation was significantly correlated (linear regression, R(2) = 46.0, P < 0.05) with protein intake such that the mean ratio of 18-h oxidation: 18-h intake was 1.2 on both diets. Fat oxidation was significantly correlated (linear regression, R(2) = 18.9, P < 0.05) with fat intake such that the mean ratio of 18-h fat oxidation: 18-h fat intake was 1.1 (MP) and 0.9 (HP). This study demonstrated that cats adapt net protein oxidation at these levels of protein intake, and the reason for the high dietary protein requirement of this species is, therefore, unclear.