Grade of adiposity affects the impact of fat mass on resting energy expenditure in women.

Body fat mass (FM) adds to the variance in resting energy expenditure (REE). However, the nature and extent of this relationship remains unclear. Using a database of 1306 women and a linear regression model, we systematically analysed the contribution of FM to the total variance in REE at different grades of adiposity (ranges of body %FM). After adjusting for age, the relative contribution of FM on REE variance increased from low (10- 30- 40- # 50 %FM) and very high (>50 %FM) grades of adiposity according to the ratio between regression coefficients. These data suggest that the specific metabolic rate of fat tissue is reduced at high adiposity. This should be considered when REE is normalized for FM in obesity.

Familial influences and obesity-associated metabolic risk factors contribute to the variation in resting energy expenditure: the Kiel Obesity Prevention Study.

BACKGROUND: A low metabolic rate may be inherited and predispose to obesity, whereas a higher metabolic rate in obesity may be acquired by obesity-associated cardiometabolic risk. OBJECTIVE: We aimed to explain the interindividual variation in resting energy expenditure (REE) by assessing 1) the association between REE and body composition, thyroid hormones, and obesity-related cardiometabolic risk factors, and 2) the familial (genetic and environmental) contribution to REE. DESIGN: REE and metabolic risk factors (ie, blood pressure and plasma insulin, glucose, and C-reactive protein concentrations) were assessed in 149 two- or three-generation families, including at least one overweight or obese member. Heritability of REE, respiratory quotient (RQ), thyroid hormones [thyrotropin (TSH), free triiodothyronine (FT3) and free thyroxine (FT4)], and body composition (fat-free mass and fat mass) were estimated by using variance components-based quantitative genetic models. RESULTS: REE adjusted for body composition, sex, and age (REEadj) significantly correlated with systolic and diastolic blood pressure, plasma insulin and glucose concentrations, and the homeostasis model assessment (HOMA) (r = 0.14-0.31, P < 0.05). Thyroid hormones had a modest influence on REE variance only. Heritability was 0.30 +/- 0.07 for REEadj and 0.29 +/- 0.08 for REE after additional adjustment for thyroid hormones and metabolic risk. Furthermore, heritability was estimated to be 0.22 +/- 0.08 for RQ, 0.37 +/- 0.08 for TSH, 0.68 +/- 0.06 for FT4, and 0.69 +/- 0.05 for FT3 (all significantly larger than zero). CONCLUSIONS: Obesity-related cardiometabolic risk factors contribute to interindividual variation in REE, with hypertension and insulin resistance being associated with a higher REE. REE was moderately heritable, independent of body composition, sex, age, thyroid function, and cardiometabolic risk.

Malnutrition and hypermetabolism are not risk factors for the presence of hepatic encephalopathy: a cross-sectional study.

BACKGROUND AND AIM: Hepatic encephalopathy is a frequent complication of cirrhosis. The present retrospective investigation was conducted to characterize metabolic alterations in cirrhotic patients with and without hepatic encephalopathy. We tested the hypothesis that reduced nutritional status or the degree of tissue catabolism are associated with the presence of hepatic encephalopathy. METHODS: We investigated 223 patients with histologically confirmed nonalcoholic cirrhosis without hepatic encephalopathy and with hepatic encephalopathy (grades 1-3). To assess liver function, nutritional status, and energy metabolism, a variety of biochemical and clinical tests were performed including anthropometric measurements, bioelectrical impedance analysis, and indirect calorimetry. RESULTS: Nutritional status and tissue catabolism were not significantly different between patients with and without hepatic encephalopathy. CONCLUSIONS: Our data do not support the hypothesis that malnutrition or tissue catabolism are independent risk factors for the presence of hepatic encephalopathy in patients with nonalcoholic cirrhosis.

Use of height3:waist circumference3 as an index for metabolic risk assessment?

Current anthropometric indices for health risk assessment are indirect measures of total or visceral body fat mass that do not consider the inverse relationship of lean body mass to metabolic risk as well as the non-linear relationship between central obesity and insulin resistance. We examined a new anthropometric index that reflects the relationship of waist circumference (WC) as a risk factor to fat-free mass (FFM) as a protective parameter of body composition. In a population of 335 adults (191 females and 144 males; mean age 53 (SD 13.9) years) with a high prevalence of obesity (27%) and metabolic syndrome (30%) we derived FFM:WC(3) from the best fit of the relationship with metabolic risk factors (plasma triacylglycerol levels and insulin resistance by homeostasis model assessment index). Because FFM is known to be proportional to the cube of height, FFM was subsequently replaced by height(3) yielding height(3):WC(3) as an easily applicable anthropometric index. Significant inverse relationships of height(3):WC(3) to metabolic risk factors were observed for both sexes. They slightly exceeded those of conventional anthropometric indices such as BMI, WC or WC:hip ratio in women but not in men. The exponential character of the denominator WC(3) implies that at a given FFM with gradually increasing WC the increase in metabolic risk is lower than proportional. Further studies are needed to evaluate height(3):WC(3) as an anthropometric index for health risk assessment.

World Health Organization equations have shortcomings for predicting resting energy expenditure in persons from a modern, affluent population: generation of a new reference standard from a retrospective analysis of a German database of resting energy expenditure.

BACKGROUND: Reference standards for resting energy expenditure (REE) are widely used. Current standards are based on measurements made in the first part of the past century in various races and locations. OBJECTIVE: The aim of the present study was to investigate the application of the World Health Organization (WHO) equations from 1985 in healthy subjects living in a modern, affluent society in Germany and to generate a new formula for predicting REE. DESIGN: The study was a cross-sectional and retrospective analysis of data on REE and body composition obtained from 2528 subjects aged 5-91 y in 7 different centers between 1985 and 2002. RESULTS: Mean REE varied between 5.63 and 8.07 MJ/d in males and between 5.35 and 6.46 MJ/d in females. WHO prediction equations systematically overestimated REE at low REE values but underestimated REE at high REE values. There were significant and independent effects of sex, age, body mass or fat-free mass, and fat mass on REE. Multivariate regression analysis explained up to 75% of the variance in REE. Two prediction formulas including weight, sex, and age or fat-free mass, fat mass, sex, and age, respectively, were generated in a subpopulation and cross-validated in another subpopulation. Significant deviations were still observed for underweight and normal-weight subjects. REE prediction formulas for specific body mass index groups reduced the deviations. The normative data for REE from the Institute of Medicine underestimated our data by 0.3 MJ/d. CONCLUSIONS: REE prediction by WHO formulas systematically over- and underestimates REE. REE prediction from a weight group-specific formula is recommended in underweight subjects.

Alterations in glucose metabolism associated with liver cirrhosis persist in the clinically stable long-term course after liver transplantation.

With increasing long-term survival rates after orthotopic liver transplantation (OLT), metabolic alterations complicating the clinical course, such as diabetes mellitus (DM), become increasingly important. Liver cirrhosis is associated with severe alterations in glucose metabolism. However, it is currently unclear whether these changes are reversed by successful OLT. We therefore characterized glucose metabolism in patients with liver cirrhosis and normal fasting glucose levels before OLT (cir), in the clinically stable long-term course after OLT (OLT), and control subjects (con) using oral glucose tolerance tests (cir = 100, OLT = 62, con = 32), euglycemic-hyperinsulinemic clamps (cir = 10, OLT = 27, con = 14), and positron emission tomography (PET) scan analysis with 18F-fluorodeoxyglucose (FDG) as a tracer (cir = 7, OLT = 7, con = 5). Fasting insulin and C-peptide levels were significantly elevated in patients with liver cirrhosis compared with both control subjects (P <.001) and patients after OLT (P <.001). After OLT, insulin was normalized, whereas C-peptide remained elevated (P < 0.01). In the patients with liver cirrhosis, 27% had a normal glucose tolerance, 38% had an impaired glucose tolerance (IGT), and 35% were diabetic. After OLT, 34% had a normal glucose tolerance, 29% an IGT, and 37% were diabetic. Comparison of the same patients before and after OLT demonstrated that IGT or diabetes before OLT was the major risk factor for these conditions after OLT, which was independent of either immunosuppression (cyclosporine vs FK506) or low-dose prednisolone. Total glucose uptake was reduced in patients with liver cirrhosis to less than half the values in control subjects (21.2 +/- 2.8 vs 43.7 +/- 2.4 micromol/kg/minute, respectively, P <.001), whereas patients after OLT showed intermediate values (35.7 +/- 1.4 micromol/kg/minute, P < 0.05 vs con, P < 0.01 vs cir). This difference was caused by a reduction in nonoxidative glucose metabolism in patients with liver cirrhosis compared with control subjects (7.4 +/- 1.9 vs 28.7 +/- 1.8 micromol/kg/minute, respectively, P <.01) and patients after OLT (20.1 +/- 1.4 micromol/kg/minute, P < 0.05 vs con and OLT). In the PET study, skeletal muscle glucose uptake was significantly reduced in patients with liver cirrhosis compared with control subjects (3.5 +/- 0.4 vs 11.8 +/- 2.5 micromol/100g/minute, respectively, P <.05). After OLT, muscle glucose uptake improved compared with patients with liver cirrhosis (5.9 +/- 1.0 micromol/100g/minute, P <.05) but remained significantly lower than in control subjects (P <.05). In conclusion, these results demonstrate that preexisting IGT or diabetes are the major risk factors for IGT and diabetes after OLT. This finding was independent of the immunosuppressive medication. The peripheral insulin resistance in cirrhosis is characterized by a decrease in nonoxidative glucose disposal that is improved, but not normalized, after OLT.

Use of positron emission tomography for the assessment of skeletal muscle glucose metabolism.

Positron emission tomography (PET) is a unique tool for studying regional skeletal muscle glucose metabolism and blood flow in vivo. The application of PET in the assessment of skeletal muscle glucose metabolism depends on recent improvements in instrumentation, data analysis, and production of (18)F-fluorodeoxyglucose (FDG) and (15)O water. The data presented support the validity of the (15)O water model to measure blood flow and the FDG model for the determination of glucose uptake and glucose kinetic constants (influx, efflux, and phosphorylation) in skeletal muscle. However, quantification of absolute glucose transport and backflux rates should be applied with caution because those calculations are based on unproven assumptions such as validity of the lumped constant for these individual processes and constancy of the free and accessible intracellular glucose pool. It is evident that quantification of glucose fluxes using the triple tracer technology generates conflicting data that violate assumptions inherent in triple tracer or PET modeling. Further FDG-PET studies will have to solve those problems to provide more insight into the regulatory processes of glucose transport and phosphorylation of different insulin-resistant disease states. Promising new areas of PET research will include not only detailed study of glucose kinetics but also the measurement of muscle protein synthesis in vivo, which is of interest in a variety of conditions.

Norms and correlates of bioimpedance phase angle in healthy human subjects, hospitalized patients, and patients with liver cirrhosis.

This study investigates whether bioimpedance indexes rather than derived body compartments would be adequate for nutritional assessment. Evidence is provided that the phase angle as determined by conventional tetrapolar whole body bioelectrical impedance analysis at 50 kHz (1) was largely determined by the arms and legs and not the trunk, (2) was higher in control subjects than in hospitalized patients [mean (SD) 6.6 degrees (0.6) degrees vs 4.9 degrees (1.2) degrees, P<0.001], (3) discriminated poorly between cirrhotic patients of different Child-Pugh class, and (4) was positively correlated with muscle mass ( r=0.53) and muscle strength ( r=0.53) in these patients (each P<0.01). In a prospective study of patients with liver cirrhosis Kaplan-Meier and log rank analyses of survival curves demonstrated that patients with phase angles equal to or less than 5.4 degrees had shorter survival times than patients with higher phase angles [6.6 degrees (1.4) degrees ] and that phase angles less than 4.4 degrees were associated with even shorter survival times ( P<0.01). The prognostic roles of the phase angle and standard nutritional parameters such as total body potassium, anthropometric measurements, and impedance derived fat free mass, body cell mass and fat mass were evaluated separately by Cox regression which eliminated all variables except the phase angle as predictors of patient survival time ( P<0.01). We concluded that for the clinical assessment of patients the phase angle may be superior to commonly used body composition information.