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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.

Inhibitors of sodium-dependent glucose co-transporter 2 (SGLT2) increase glucose excretion in the urine and improve blood glucose in Type 2 diabetes mellitus. Glycosuria provides an energy and osmotic drain that could alter body composition. We therefore conducted a pilot study comparing the effects on body composition of two SGLT2 inhibitors, remogliflozin etabonate (RE) 250 mg TID (n = 9) and sergliflozin etabonate (SE) (1000 mg TID) (n = 9), with placebo (n = 12) in obese non-diabetic subjects. Both drugs were well tolerated during 8 weeks of dosing, and the most common adverse event was headache. No urinary tract infections were observed, but there was one case of vaginal candidiasis in the RE group. As expected, RE and SE increased urine glucose excretion, with no change in the placebo group. All the subjects lost weight over 8 weeks, irrespective of treatment assignment. There was a reduction in TBW measured by D2O dilution in the RE group that was significantly greater than placebo (1.4 kg, p = 0.029). This was corroborated by calculation of fat-free mass using a quantitative magnetic resonance technique. All but one subject had a measurable decrease in fat mass. There was significant between-subject variability of weight and fat loss, and no statistically significant differences were observed between groups. Despite a lack of a difference in weight and fat mass loss, the leptin/adiponectin ratio, a measure of insulin resistance, was significantly decreased in the RE group when compared to placebo and SE, suggesting that this SGTL-2 inhibitor may improve metabolic health independent of a change in fat mass.

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.

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.

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.

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.

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.

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)

A new method for measuring total energy expenditure (TEE) with stable isotopically labelled water ( 2 H 2 18 O) was used to measure average daily energy expenditure over 14-21 day periods in 12 healthy women following their normal activity patterns. TEE expressed as a multiple of basal metabolic rate (TEE/BMR) averaged only 1·38±0·04. This result is at variance with the widely held assumption that minimum maintenance requirements are 1·5 times BMR.