Comparison of measured sleeping metabolic rate and predicted basal metabolic rate during the first year of life: evidence of a bias changing with increasing metabolic rate

Objective: To compare measurements of sleeping metabolic rate (SMR) in infancy with predicted basal metabolic rate (BMR) estimated by the equations of Schofield. Methods: Some 104 serial measurements of SMR by indirect calorimetry were performed in 43 healthy infants at 1.5, 3, 6, 9 and 12 months of age. Predicted BMR was calculated using the weight only (BMR-wo) and weight and height (BMR-wh) equations of Schofield for 0-3-y-olds. Measured SMR values were compared with both predictive values by means of the Bland-Altman statistical test. Results: The mean measured SMR was 1.48 MJ/day. The mean predicted BMR values were 1.66 and 1.47 MJ/day for the weight only and weight and height equations, respectively. The Bland-Altman analysis showed that BMR-wo equation on average overestimated SMR by 0.18 MJ/day (11%) and the BMR-wh equation underestimated SMR by 0.01 MJ/day (1%). However the 95% limits of agreement were wide: - 0.64 to - 0.28MJ/day (28%) for the former equation and - 0.39 to +0.41 MJ/day (27%) for the latter equation. Moreover there was a significant correlation between the mean of the measured and predicted metabolic rate and the difference between them. Conclusions: The wide variation seen in the difference between measured and predicted metabolic rate and the bias probably with age indicates there is a need to measure actual metabolic rate for individual clinical care in this age group.

Changes in body fluid and energy compartments during prolonged hunger strike

Prolonged total food deprivation in non-obese adults is rare, and few studies have documented body composition changes in this setting. In a group of eight hunger strikers who refused alimentation for 43 days, water and energy compartments were estimated, aiming to assess the impact of progressive starvation. Measurements included body mass index (BMI), triceps skinfold (TSF), arm muscle circumference (AMC), and bioimpedance (BIA) determinations of water, fat, lean body mass (LBM), and total resistance. Indirect calorimetry was also performed in one occasion. The age of the group was 43.3±6.2 years (seven males, one female). Only water, intermittent vitamins and electrolytes were ingested, and average weight loss reached 17.9%. On the last two days of the fast (43rd-44th day) rapid intravenous fluid, electrolyte, and vitamin replenishment were provided before proceeding with realimentation. Body fat decreased approximately 60% (BIA and TSF), whereas BMI reduced only 18%. Initial fat was estimated by BIA as 52.2±5.4% of body weight, and even on the 43rd day it was still measured as 19.7±3.8% of weight. TSF findings were much lower and commensurate with other anthropometric results. Water was comparatively low with high total resistance, and these findings rapidly reversed upon the intravenous rapid hydration. At the end of the starvation period, BMI (21.5±2.6 kg/m²) and most anthropometric determinations were still acceptable, suggesting efficient energy and muscle conservation. Conclusions: 1) All compartments diminished during fasting, but body fat was by far the most affected; 2) Total water was low and total body resistance comparatively elevated, but these findings rapidly reversed upon rehydration; 3) Exaggerated fat percentage estimates from BIA tests and simultaneous increase in lean body mass estimates suggested that this method was inappropriate for assessing energy compartments in the studied population; 4) Patients were not morphologically malnourished after 43 days of fasting; however, the prognostic impact of other impairments was not considered in this analysis.

Energy expenditure after 2- to 3-hour elective surgical operations

Energy expenditure was measured by indirect calorimetry in 17 adult patients (8 women and 9 men) before surgery, 4 hours immediately after surgery , and 24 hours late after surgery in patients undergoing elective surgery of small-to-medium scope. MATERIAL AND METHODS: The total duration of surgery ranged from 2 to 3 hours. Repeated measures were performed on the same patient, so that each patient was considered to be his/her own control. All patients received a 5% dextrose solution (2000 mL/day) throughout the postoperative period. RESULTS: Men showed a reduction in CO2 production during the immediately after surgery period (257±42 mL/min) compared to before surgery (306±48 mL/min) and late after surgery (301±45 mL/min); this reduction was not observed in women. Energy expenditure was also lower in men during immediately after surgery (6.6 kJ/min). None of the other measurements, including substrate oxidation, showed significant differences. CONCLUSION: Therefore, elective surgery itself cannot be considered an important trauma that would result in increased energy expenditure. According to this study, it is not necessary to prescribe an energy supply exceeding basal expenditure during the immediate after-surgery period. The present results suggest that the energy supply prescribed during the postoperative period after elective surgery of small-to-medium scope should not exceed 5-7 kJ/min, so the patient does not receive a carbohydrate overload from energy supplementation.

Evolução, a curto prazo, do perfil do estado de nutrição no transplante hepático, em adultos : contributo para otimização da abordagem clínica e nutricional

RESUMO:Contexto: A avaliação do estado de nutrição do doente com indicação para transplante hepático (TH) deve ser abrangente, considerando o amplo espetro de situações clínicas e metabólicas. As alterações metabólicas relacionadas com a doença hepática podem limitar a aplicação de métodos de avaliação nutricional, subestimando a desnutrição. Após o TH, é expectável a reversão dos distúrbios metabólicos da doença hepática, pela melhoria da função do fígado. No entanto, algumas complicações metabólicas podem surgir após o TH, relacionadas com a má-nutrição, a desnervação hepática e o uso prolongado de imunossupressão, comprometendo os resultados clínicos a longo-prazo. A medição longitudinal e confiável do metabolismo energético e dos compartimentos corporais após o TH, avaliada em conjunto com fatores influentes no estado de nutrição, pode identificar precocemente situações de risco e otimizar e individualizar estratégias clínicas e nutricionais com vantagens no prognóstico. Objetivo: Avaliar longitudinalmente, a curto prazo, o estado de nutrição após o TH em doentes com insuficiência hepática por doença crónica e identificar os fatores, para além da cirurgia, que determinam diferentes evoluções do metabolismo energético e da composição corporal. Métodos: Foi estudada uma coorte de indivíduos com indicação para TH por doença hepática crónica, admitidos consecutivamente para TH ortotópico eletivo, durante 2 anos. Foram programados 3 momentos de avaliação: na última consulta pré-TH (T0), logo que adquirida autonomia respiratória e funcional após o TH (T1) e um mês após o TH (T2). Nesses momentos, foram medidos no mesmo dia: o suprimento nutricional por recordatório das últimas 24 horas, o estado de nutrição por Avaliação Subjetiva Global (ASG), o gasto energético em repouso (GER) por calorimetria indireta, a antropometria, a composição corporal por bioimpedância elétrica tetrapolar multifrequências e a força muscular por dinamometria de preensão palmar. O índice de massa magra (IMM) e a massa celular corporal (MCC) foram usados como indicadores do músculo esquelético e a percentagem de massa gorda (%MG) e o índice de massa gorda (IMG) como indicadores de adiposidade. O GER foi comparado com o estimado pelas fórmulas de Harris-Benedict para classificação do estado metabólico em:hipermetabolismo (GER medido >120% do GER estimado), normometabolismo (GER medido entre 80 e 120% do GER estimado) e hipometabolismo (GER medido <80% do GER estimado). Foi utilizada análise multivariável: por regressão logística, para identificar variáveis associadas à possibilidade (odds ratio – OR) de pertencer a cada grupo metabólico pré-TH; por regressão linear múltipla, para identificar variáveis associadas à variação dos compartimentos corporais no período pós-TH; e por modelos de efeitos mistos generalizados, para identificar variáveis associadas à evolução do GER e dos compartimentos corporais entre o período pré- e pós-TH. Resultados: Foram incluídos 56 indivíduos com idade, média (DP), 53,7 (8,5) anos, 87,5% do sexo masculino, 23,2% com doença hepática crónica de etiologia etanólica. Após o TH, em 60,7% indivíduos foi administrado regime imunossupressor baseado no tacrolimus. Os indivíduos foram avaliados [mediana (AIQ)] 90,5 (P25: 44,2; P75: 134,5) dias antes do TH (T0), 9,0 (P25: 7,0; P75: 12,0) dias após o TH (T1) e 36,0 (P25: 31,0; P75: 43,0) dias após o TH (T2). Após o TH houve melhoria significativa do estado de nutrição, com diminuição da prevalência de desnutrição classificada pela ASG (37,5% em T0, 16,1% em T2, p<0,001). Antes do TH, 41,1% dos indivíduos eram normometabólicos, 37,5% hipometabólicos e 21,4% hipermetabólicos. A possibilidade de pertencer a cada grupo metabólico pré-TH associou-se à: idade (OR=0,899, p=0,010) e desnutrição pela ASG (OR=5,038, p=0,015) para o grupo normometabólico; e índice de massa magra (IMM, OR=1,264, p=0,049) e etiologia viral da doença hepática (OR=8,297, p=0,019) para o grupo hipermetabólico. Não se obteve modelo múltiplo para o grupo de hipometabólico pré-TH, mas foram identificadas associações univariáveis com a história de toxicodependência (OR=0,282, p=0,047) e com a sarcopénia pré- TH (OR=8,000, p=0,040). Após o TH, houve normalização significativa e progressiva do estado metabólico, indicada pelo aumento da prevalência de normometabolismo (41,1% em T0, 57,1% em T2, p=0,040). Foram identificados diferentes perfis de evolução do GER após o TH, estratificado pelo estado metabólico pré-TH: no grupo hipometabólico pré-TH, o GER (Kcal) aumentou significativa e progressivamente (1030,6 em T0; 1436,1 em T1, p=0,001; 1659,2 em T2, p<0,001); no grupo hipermetabólico pré-TH o GER diminuiu significativa e progressivamente (2097,1 em T0; 1662,5 em T1, p=0,024; 1493,0 em T2, p<0.001); no grupo normometabólico não houve variações significativas. Os perfis de evolução do GER associaram-se com: peso corporal (β=9,6, p<0,001) e suprimento energético (β=13,6, p=0,005) na amostra total; com peso corporal (β=7,1, p=0,018) e contributo energético dos lípidos (β=18,9, p=0,003) no grupo hipometabólico pré-TH; e com peso corporal (β=14,1, p<0,001) e desnutrição pela ASG (β=-171,0, p=0,007) no grupo normometabólico pré-TH.Houve redução transitória dos compartimentos corporais entre T0 e T1, mas a maioria destes recuperou para valores semelhantes aos pré-TH. As exceções foram a água extracelular, que diminuiu entre T0 e T2 (média 18,2 L e 17,8 L, p=0,042), a massa gorda (média 25,1 Kg e 21,7 Kg, p<0,001) e o IMG (média 10,6 Kg.m-2 e 9,3 Kg.m-2, p<0,001) que diminuíram entre T1 e T2. Relativamente à evolução dos indicadores de músculo esquelético e adiposidade ao longo do estudo: a evolução do IMM associou-se com força de preensão palmar (β=0,06, p<0,001), creatininémia (β=2,28, p<0,001) e número total de fármacos administrados (β=-0,21, p<0,001); a evolução da MCC associou-se com força de preensão palmar (β=0,16, p<0,001), creatininémia (β=4,17, p=0,008) e número total de fármacos administrados (β=-0,46, p<0,001); a evolução da %MG associou-se com força de preensão palmar (β=-0,11, p=0,028), história de toxicodependência (β=-5,75, p=0,024), creatininémia (β=-5,91, p=0,004) e suprimento proteico (β=-0,06, p=0,001); a evolução do IMG associou-se com história de toxicodependência (β=- 2,64, p=0,019), creatininémia (β=-2,86, p<0,001) e suprimento proteico (β=-0,02, p<0,001). A variação relativa (%Δ) desses compartimentos corporais entre T1 e T2 indicou o impacto da terapêutica imunossupressora na composição corporal: o regime baseado na ciclosporina associou-se positivamente com a %Δ do IMM (β=23,76, p<0,001) e %Δ da MCC (β=26,58, p<0,001) e negativamente com a %Δ MG (β=-25,64, p<0,001) e %Δ do IMG (β=-25,62, p<0,001), relativamente ao regime baseado no tacrolimus. Os esteróides não influenciaram a evolução do GER nem com a dos compartimentos corporais. Conclusões: O estado de nutrição, avaliado por ASG, melhorou significativamente após o TH, traduzida pela diminuição da prevalência de desnutrição. O normometabolismo pré-TH foi prevalente e associou-se à menor idade e à desnutrição pré- TH. O hipometabolismo pré-TH associou-se à história de toxicodependência e à sarcopénia pré-TH. O hipermetabolismo pré-TH associou-se ao maior IMM e à etiologia viral da doença hepática. Após o TH, houve normalização progressiva do estado metabólico. Foram identificados três perfis de evolução do GER, associando-se com: peso corporal e suprimento energético na amostra total; peso corporal e contributo energético dos lípidos no grupo hipometabólico pré- TH; e peso corporal e desnutrição pela ASG no grupo normometabólico pré-TH. Foram identificados diferentes perfis de evolução da composição corporal após TH. A evolução do músculo esquelético associou-se positivamente com a força de preensão palmar e a creatininémia e negativamente com o número total de fármacos administrados. A evolução da adiposidade (%MG e IMG) associou-se inversamente com a história de toxicodependência, a creatininémia e o suprimento proteico; adicionalmente, a %MG associou-se inversamente com a força de preensão palmar. O regime baseado na ciclosporina associou-se independentemente com diminuição da adiposidade e aumento do músculo esquelético, comparativamente ao regime baseado no tacrolimus.---------------------------ABSTRACT:Background: The assessment of nutritional status in patients undergoing liver transplantation (LTx) should be comprehensive, accounting for the wide spectrum of the clinical and metabolic conditions. The metabolic disturbances related to liver disease may limit the precision and accuracy of traditional nutritional assessment methods underestimating the undernourishment. After LTx, it is expected that many metabolic derangements improve with the recovery of liver function. However, some metabolic complications arising after LTx, related to nutritional status, hepatic denervation, and prolonged immunosuppression, may compromise the longterm outcome. A reliable longitudinal assessment of both energy metabolism and body compartments after LTx, combined with assessments of other factors potentially affecting the nutritional status, may enable a better interpretation on the relationship between the metabolic and the nutritional status. These reliable assessments may precociously identify nutritional risk conditions and optimize and customize clinical and nutritional strategies improving the prognosis. Objective: To assess longitudinally the nutritional status shortly after orthotopic LTx in patients with chronic liver disease, and identify factors, beyond surgery, determining different energy metabolism and body composition profiles.Methods: A cohort of consecutive patients who underwent LTx due to chronic liver disease was studied within a period of two years. The assessments were performed in three occasions: at the last visit before LTx (T0), after surgery as soon as respiratory and functional autonomy was established (T1), and approximately one month after surgery (T2). On each occasion all assessments were performed on the same day, and included: the dietary assessment by 24- hour dietary recall, nutritional status by the Subjective Global Assessment (SGA), the resting energy expenditure (REE) by indirect calorimetry, anthropometry, body composition by multifrequency bioelectrical impedance analysis, and muscle strength by handgrip strength. Both the lean mass index (LMI) and body cell mass (BCM) were used as surrogates of skeletal muscle, and both the percentage of fat mass (%FM) and fat mass index (FMI) of adiposity. The REE was predicted according to the Harris and Benedict equation. Hypermetabolism was defined as a measured REE more than 120% of the predicted value; normometabolism as a measured REE within 80-120% of the predicted value; and hypometabolism as a measured REE less than 80% of the predicted value. Multiple regression analysis was used: by logistic regression to identify variables associated with odds of belong each pre-LTx metabolic groups; by linear multiple regression analysis to identify variables associated with body compartments relative variations (%Δ) in the post-LTx period; and by mixed effects models to identify variables associated with the REE and body compartments profiles pre- and post-LTx. Results: Fifty six patients with a mean (SD) of 53.7 (8.5) years of age were included, 87.5% were men and 23.2% with alcoholic liver disease. After LTx 60.7% individuals were assigned to tacrolimus-based immunosuppressive regimen. The patients were assessed at a median time (inter-quartil range) of 90.5 (P25 44.2; P75 134.5) days before LTx (T0), at a median time of 9.0 (P25 7.0; P75 12.0) (T1) and 36 (P25 31.0; P75 43.0) (T2) days after LTx. After LTx the nutritional status significantly improved: the SGA-undernourishment decreased from 37.5% (T0) to 16.1% (T2) (p<0.001). Before LTx, 41.1% patients were normometabolic, 37.5% hypometabolic, and 21.4% hypermetabolic. The predictors of each pre-LTx metabolic group were: age (OR=0.899, p=0.010) and SGA-undernourishment (OR=5.038, p=0.015) for the normometabolic group; and LMI (OR=1.264, p=0.049) and viral etiology of liver disease (OR=8.297, p=0.019) for the hypermetabolic group. No multiple model was found for the pre-LTx hypometabolic group, but univariate association was found with history of drug addiction (OR=0.282, p=0.047) and pre- LTx sarcopenia (OR=8.000, p=0.040). After LTx a significant normalization of the metabolic status occurred, indicated by the increase in the prevalence of normometabolic patients (from T0: 41.1% to T2: 57.1%, p=0.040). Different REE profiles were found with REE stratified by preoperative metabolic status: in the hypometabolic group a significant progressive increase in mean REE (Kcal) was observed (T0: 1030.6; T1: 1436.1, p=0.001; T2: 1659.2, p<0.001); in the hypermetabolic group, a significant progressive decrease in mean REE (Kcal) was observed (T0: 2097.1; T1: 1662.5, p=0.024; T2: 1493.0, p<0.001); and in the normometabolic group, no significant differences were found. The REE profiles were associated with: body weight (β- estimate=9.6, p<0.001) and energy intake (β-estimate=13.6, p=0.005) in the whole sample; with body weight (β-estimate=7.1, p=0.018) and %TEV from lipids (β-estimate=18.9, p=0.003) in the hypometabolic group; and with body weight (β-estimate=14.1, p<0.001), and SGAundernourishment (β-estimate=-171, p=0.007) in the normometabolic group. A transient decrease in most body compartments occurred from T0 to T1, with subsequent catch-up to similar preoperative values. Exceptions were the extracellular water, decreasing from T0 to T2 (mean 18.2 L to 17.8 L, p=0.042), the fat mass (mean 25.1 Kg to 21.7 Kg, p<0.001) and FMI (mean 10.6 Kg.m-2 to 9.3 Kg.m-2, p<0.001), decreasing from T1 to T2. Significant predictors of skeletal muscle and adiposity profiles were found: LMI evolution was associated with handgrip strength (β-estimate=0.06, p<0.001), serum creatinine (β- estimate=2.28, p<0.001) and number of medications (β-estimate=-0.21, p<0.001); BCM evolution was associated with handgrip strength (β-estimate=0.16, p<0.001), serum creatinine (β-estimate=4.17, p<0.001) and number of medications (β-estimate=-0.46, p<0.001); the %FM evolution was associated with handgrip strength (β-estimate=-0.11, p=0.028), history of drug addiction (β-estimate=-5.75, p=0.024), serum creatinine (β-estimate=-5.91, p=0.004) and protein intake (β-estimate=-0.06, p=0.001); and FMI evolution was associated with history of drug addiction (β-estimate=-2.64, p=0.019), serum creatinine (β-estimate=-2.86, p<0.001) and protein intake (β-estimate=-0.02, p<0.001). The %Δ of the aforementioned body compartments from T1 to T2 indicated the influence of immunosuppressive agents on body composition: the cyclosporine-based regimen, compared with tacrolimus-based regimen, was positively associated with %Δ LMI (β-estimate=23.76, p<0.001) and %Δ BCM (β- estimate=26.58, p<0.001), and inversely associated with %Δ FM (β-estimate=-25.64, p<0.001) and %Δ FMI (β-estimate=-25.62, p<0.001). No significant changes in REE or body composition were observed associated with dose or duration of steroid therapy. Conclusions: The SGA-assessed nutritional status improved shortly after LTx, with significant decrease in prevalence undernourished individuals. XXI Preoperative normometabolism was prevalent and was associated with younger age and SGAundernourishment before LTx. Preoperative hypometabolism was associated with history of drug addiction and pre-LTx sarcopenia. Preoperative hypermetabolism was associated with higher LMI and viral etiology of liver disease. A significant normalization of the metabolic status was observed after LTx. The REE profiles were positively predicted by body weight and energy intake in the whole sample, by body weight and percentage of energy intake from lipids in the preoperative hypometabolic patients, and by body weight and SGA–undernourishment in the preoperative normometabolic patients. Different body composition profiles were found after LTx. Skeletal muscle profile was positively associated with handgrip strength and serum creatinine, and inversely with the number of medications. The adiposity profile was inversely associated with history of drug addiction, serum creatinine and protein intake. Additionally, the %FM evolution was inversely associated with handgrip strength. The cyclosporine-based regimen, compared with tacrolimus-based regimen, was independently associated with skeletal muscle increase and adiposity decrease.

A mathematical model to describe fat oxidation kinetics during graded exercise.

PURPOSE: The purpose of this study was to develop a mathematical model (sine model, SIN) to describe fat oxidation kinetics as a function of the relative exercise intensity [% of maximal oxygen uptake (%VO2max)] during graded exercise and to determine the exercise intensity (Fatmax) that elicits maximal fat oxidation (MFO) and the intensity at which the fat oxidation becomes negligible (Fatmin). This model included three independent variables (dilatation, symmetry, and translation) that incorporated primary expected modulations of the curve because of training level or body composition. METHODS: Thirty-two healthy volunteers (17 women and 15 men) performed a graded exercise test on a cycle ergometer, with 3-min stages and 20-W increments. Substrate oxidation rates were determined using indirect calorimetry. SIN was compared with measured values (MV) and with other methods currently used [i.e., the RER method (MRER) and third polynomial curves (P3)]. RESULTS: There was no significant difference in the fitting accuracy between SIN and P3 (P = 0.157), whereas MRER was less precise than SIN (P < 0.001). Fatmax (44 +/- 10% VO2max) and MFO (0.37 +/- 0.16 g x min(-1)) determined using SIN were significantly correlated with MV, P3, and MRER (P < 0.001). The variable of dilatation was correlated with Fatmax, Fatmin, and MFO (r = 0.79, r = 0.67, and r = 0.60, respectively, P < 0.001). CONCLUSIONS: The SIN model presents the same precision as other methods currently used in the determination of Fatmax and MFO but in addition allows calculation of Fatmin. Moreover, the three independent variables are directly related to the main expected modulations of the fat oxidation curve. SIN, therefore, seems to be an appropriate tool in analyzing fat oxidation kinetics obtained during graded exercise.

Resting metabolic rate and protein turnover in apparently healthy elderly Gambian men.

Body composition, resting energy expenditure (REE), and whole body protein metabolism were studied in 26 young and 28 elderly Gambian men matched for body mass index during the dry season in a rural village in The Gambia. REE was measured by indirect calorimetry (hood system) in the fasting state and after five successive meals. Rates of whole body nitrogen flux, protein synthesis, and protein breakdown were determined in the fed state from the level of isotopic enrichment of urinary ammonia over a period of 12 h after a single oral dose of [15N]glycine. Expressed in absolute value, REE was significantly lower in the elderly compared with the young group (3.21 +/- 0.07 vs. 4.04 +/- 0.07 kJ/min, P < 0.001) and when adjusted to body weight (3.29 +/- 0.05 vs. 3.96 +/- 0.05 kJ/min, P < 0.0001) and fat-free mass (FFM; 3.38 +/- 0.01 vs. 3.87 +/- 0.01 kJ/min, P < 0.0001). The rate of protein synthesis averaged 207 +/- 13 g protein/day in the elderly and 230 +/- 13 g protein/day in the young group, whereas protein breakdown averaged 184 +/- 13 g protein/day in the elderly and 203 +/- 13 g protein/day in the young group (nonsignificant). When values were adjusted for body weight or FFM, they did not reveal any difference between the two groups. It is concluded that the reduced REE adjusted for body composition observed in elderly Gambian men is not explained by a decrease in protein turnover.

Metabolic and respiratory effects of infused sodium acetate in healthy human subjects.

The metabolic and respiratory effects of intravenous 0.5 M sodium acetate (at a rate of 2.5 mmol/min during 120 min) were studied in nine normal human subjects. O2 consumption (VO2) and CO2 production (VCO2) were measured continuously by open-circuit indirect calorimetry. VO2 increased from 251 +/- 9 to 281 +/- 9 ml/min (P < 0.001), energy expenditure increased from 4.95 +/- 0.17 kJ/min baseline to 5.58 +/- 0.16 kJ/min (P < 0.001), and VCO2 decreased nonsignificantly (211 +/- 7 ml/min vs. 202 +/- 7 ml/min, NS). The extrapulmonary CO2 loss (i.e., bicarbonate generation and excretion) was estimated at 48 +/- 5 ml/min. This observation is consistent with 1 mol of bicarbonate generated from 1 mol of acetate metabolized. Alveolar ventilation decreased from 3.5 +/- 0.2 l/min basal to 3.1 +/- 0.2 l/min (P < 0.001). The minute ventilation (VE) to VO2 ratio decreased from 22.9 +/- 1.3 to 17.6 +/- 0.9 l/l (P < 0.005), arterial PO2 decreased from 93.2 +/- 1.9 to 78.7 +/- 1.6 mmHg (P < 0.0001), arterial PCO2 increased from 39.2 +/- 0.7 to 42.1 +/- 1.1 mmHg (P < 0.0001), pH from 7.40 +/- 0.005 to 7.50 +/- 0.007 (P < 0.005), and arterial bicarbonate concentration from 24.2 +/- 0.7 to 32.9 +/- 1.1 (P < 0.0001). These observations indicate that sodium acetate infusion results in substantial extrapulmonary CO2 loss, which leads to a relative decrease of total and alveolar ventilation.

Effects of hyperglycemia on glucose metabolism before and after oral glucose ingestion in normal men.

The plasma glucose excursion may influence the metabolic responses after oral glucose ingestion. Although previous studies addressed the effects of hyperglycemia in conditions of hyperinsulinemia, it has not been evaluated whether the route of glucose administration (oral vs. intravenous) plays a role. Our aim was to determine the effects of moderately controlled hyperglycemia on glucose metabolism before and after oral glucose ingestion. Eight normal men underwent two oral glucose clamps at 6 and 10 mmol/l plasma glucose. Glucose turnover and cycling rates were measured by infusion of [2H7]glucose. The oral glucose load was labeled by D-[6,6-2H2]glucose to monitor exogenous glucose appearance, and respiratory exchanges were measured by indirect calorimetry. Sixty percent of the oral glucose load appeared in the systemic circulation during both the 6 and 10 mmol/l plasma glucose tests, although less endogenous glucose appeared during the 10 mmol/l tests before glucose ingestion (P &lt; 0.05). This inhibitory effect of hyperglycemia was not detectable after oral glucose ingestion, although glucose utilization was increased (+28%, P &lt; 0.05) due to increased nonoxidative glucose disposal [10 vs. 6 mmol/l: +20%, not significant (NS) before oral glucose ingestion; +40%, P &lt; 0.05 after oral glucose ingestion]. Glucose cycling rates were increased by hyperglycemia (+13% before oral glucose ingestion, P &lt; 0.001; +31% after oral glucose ingestion, P &lt; 0.05) and oral glucose ingestion during both the 6 (+10%, P &lt; 0.05) and 10 mmol/l (+26%, P &lt; 0.005) tests. A moderate hyperglycemia inhibits endogenous glucose production and contributes to glucose tolerance by enhancing nonoxidative glucose disposal. Hyperglycemia and oral glucose ingestion both stimulate glucose cycling.

Development and current use of parenteral nutrition in critical care - an opinion paper.

Critically ill patients depend on artificial nutrition for the maintenance of their metabolic functions and lean body mass, as well as for limiting underfeeding-related complications. Current guidelines recommend enteral nutrition (EN), possibly within the first 48 hours, as the best way to provide the nutrients and prevent infections. EN may be difficult to realize or may be contraindicated in some patients, such as those presenting anatomic intestinal continuity problems or splanchnic ischemia. A series of contradictory trials regarding the best route and timing for feeding have left the medical community with great uncertainty regarding the place of parenteral nutrition (PN) in critically ill patients. Many of the deleterious effects attributed to PN result from inadequate indications, or from overfeeding. The latter is due firstly to the easier delivery of nutrients by PN compared with EN increasing the risk of overfeeding, and secondly to the use of approximate energy targets, generally based on predictive equations: these equations are static and inaccurate in about 70% of patients. Such high uncertainty about requirements compromises attempts at conducting nutrition trials without indirect calorimetry support because the results cannot be trusted; indeed, both underfeeding and overfeeding are equally deleterious. An individualized therapy is required. A pragmatic approach to feeding is proposed: at first to attempt EN whenever and as early as possible, then to use indirect calorimetry if available, and to monitor delivery and response to feeding, and finally to consider the option of combining EN with PN in case of insufficient EN from day 4 onwards.

Effects of infused amino acids on glucose production and utilization in healthy human subjects.

Amino acids have been reported to increase endogenous glucose production in normal human subjects during hyperinsulinemia: however, controversy exists as to whether insulin-mediated glucose disposal is inhibited under these conditions. The effect of an amino acid infusion on glucose oxidation rate has so far not been determined. Substrate oxidation rates, endogenous glucose production, and [13C]glucose synthesis from [13C]bicarbonate were measured in six normal human subjects during sequential infusions of exogenous glucose and exogenous glucose with (n = 5) or without (n = 5) exogenous amino acids. Amino acids increased endogenous glucose production by 84% and [13C]glucose synthesis by 235%. Glucose oxidation estimated from indirect calorimetry decreased slightly after amino acids, but glucose oxidation estimated from [13C]glucose-13CO2 data was increased by 14%. It is concluded that gluconeogenesis is the major pathway of amino acid degradation. During amino acid administration, indirect calorimetry underestimates the true rate of glucose oxidation, whereas glucose oxidation calculated from the 13C enrichment of expired CO2 during [U-13C]glucose infusion does not. A slight stimulation of glucose oxidation during amino acid infusion, concomitant with an increased plasma insulin concentration, indicates that amino acids do not inhibit glucose oxidation.

Effect of carbohydrate overfeeding on whole body macronutrient metabolism and expression of lipogenic enzymes in adipose tissue of lean and overweight humans

OBJECTIVE: Lipids stored in adipose tissue can originate from dietary lipids or from de novo lipogenesis (DNL) from carbohydrates. Whether DNL is abnormal in adipose tissue of overweight individuals remains unknown. The present study was undertaken to assess the effect of carbohydrate overfeeding on glucose-induced whole body DNL and adipose tissue lipogenic gene expression in lean and overweight humans. DESIGN: Prospective, cross-over study. SUBJECTS AND METHODS: A total of 11 lean (five male, six female, mean BMI 21.0+/-0.5 kg/m(2)) and eight overweight (four males, four females, mean BMI 30.1+/-0.6 kg/m(2)) volunteers were studied on two occasions. On one occasion, they received an isoenergetic diet containing 50% carbohydrate for 4 days prior to testing; on the other, they received a hyperenergetic diet (175% energy requirements) containing 71% carbohydrates. After each period of 4 days of controlled diet, they were studied over 6 h after having received 3.25 g glucose/kg fat free mass. Whole body glucose oxidation and net DNL were monitored by means of indirect calorimetry. An adipose tissue biopsy was obtained at the end of this 6-h period and the levels of SREBP-1c, acetyl CoA carboxylase, and fatty acid synthase mRNA were measured by real-time PCR. RESULTS: After isocaloric feeding, whole body net DNL amounted to 35+/-9 mg/kg fat free mass/5 h in lean subjects and to 49+/-3 mg/kg fat free mass/5 h in overweight subjects over the 5 h following glucose ingestion. These figures increased (P<0.001) to 156+/-21 mg/kg fat free mass/5 h in lean and 64+/-11 mg/kg fat free mass/5 h (P<0.05 vs lean) in overweight subjects after carbohydrate overfeeding. Whole body DNL after overfeeding was lower (P<0.001) and glycogen synthesis was higher (P<0.001) in overweight than in normal subjects. Adipose tissue SREBP-1c mRNA increased by 25% in overweight and by 43% in lean subjects (P<0.05) after carbohydrate overfeeding, whereas fatty acid synthase mRNA increased by 66 and 84% (P<0.05). CONCLUSION: Whole body net DNL is not increased during carbohydrate overfeeding in overweight individuals. Stimulation of adipose lipogenic enzymes is also not higher in overweight subjects. Carbohydrate overfeeding does not stimulate whole body net DNL nor expression of lipogenic enzymes in adipose tissue to a larger extent in overweight than lean subjects.

Measurement of 13CO2 in expired air as an index of compliance to a high carbohydrate diet naturally enriched in 13C.

The aim of this study was to determine whether breath 13CO2 measurements could be used to assess the compliance to a diet containing carbohydrates naturally enriched in 13C. The study was divided into two periods: Period 1 (baseline of 4 days) with low 13C/12C ratio carbohydrates. Period 2 (5 days) isocaloric diet with a high 13C/12C ratio (corn, cane sugar, pineapple, millet) carbohydrates. Measurements were made of respiratory gas exchange by indirect calorimetry, urinary nitrogen excretion and breath 13CO2 every morning in post-absorptive conditions, both in resting state and during a 45-min low intensity exercise (walking on a treadmill). The subjects were 10 healthy lean women (BMI 20.4 +/- 1.7 kg/m2, % body fat 24.4 +/- 1.3%), the 13C enrichment of oxidized carbohydrate and breath 13CO2 were compared to the enrichment of exogenous dietary carbohydrates. At rest the enrichment of oxidized carbohydrate increased significantly after one day of 13C carbohydrate enriched diet and reached a steady value (103 +/- 16%) similar to the enrichment of exogenous carbohydrates. During exercise, the 13C enrichment of oxidized carbohydrate remained significantly lower (68 +/- 17%) than that of dietary carbohydrates. The compliance to a diet with a high content of carbohydrates naturally enriched in 13C may be assessed from the measurement of breath 13CO2 enrichment combined with respiratory gas exchange in resting, postabsorptive conditions.

Pragmatic approach to nutrition in the ICU: Expert opinion regarding which calorie protein target.

BACKGROUND & AIMS: Since the publications of the ESPEN guidelines on enteral and parenteral nutrition in ICU, numerous studies have added information to assist the nutritional management of critically ill patients regarding the recognition of the right population to feed, the energy-protein targeting, the route and the timing to start. METHODS: We reviewed and discussed the literature related to nutrition in the ICU from 2006 until October 2013. RESULTS: To identify safe, minimal and maximal amounts for the different nutrients and at the different stages of the acute illness is necessary. These amounts might be specific for different phases in the time course of the patient's illness. The best approach is to target the energy goal defined by indirect calorimetry. High protein intake (1.5 g/kg/d) is recommended during the early phase of the ICU stay, regardless of the simultaneous calorie intake. This recommendation can reduce catabolism. Later on, high protein intake remains recommended, likely combined with a sufficient amount of energy to avoid proteolysis. CONCLUSIONS: Pragmatic recommendations are proposed to practically optimize nutritional therapy based on recent publications. However, on some issues, there is insufficient evidence to make expert recommendations.

Effects of infused fructose on endogenous glucose production, gluconeogenesis, and glycogen metabolism.

To determine the mechanisms that prevent an increase in gluconeogenesis from increasing hepatic glucose output, six healthy women were infused with [1-13C]fructose (22 mumol.kg-1.min-1), somatostatin, insulin, and glucagon. In control experiment, non-13C-enriched fructose was infused at the same rate without somatostatin, and [U-13C]glucose was infused to measure specifically plasma glucose oxidation. Endogenous glucose production (EGP, [6,6-2H]glucose), net carbohydrate oxidation (CHOox, indirect calorimetry), and fructose oxidation (13CO2) were measured. EGP rate did not increase after fructose infusion with (13.1 +/- 1.2 vs. 12.9 +/- 0.3 mumol.kg-1.min-1) and without (10.3 +/- 0.5 vs. 9.7 +/- 0.5 mumol.kg-1.min-1) somatostatin, despite the fact that gluconeogenesis increased. Nonoxidative fructose disposal, corresponding mainly to glycogen synthesis, was threefold net glycogen deposition, the latter calculated as fructose infusion minus CHOox (14.8 +/- 1.1 and 4.3 +/- 2.0 mumol.kg-1.min-1). It is concluded that 1) the mechanism by which EGP remains constant when gluconeogenesis from fructose increases is independent of changes in insulin and 2) simultaneous breakdown and synthesis of glycogen occurred during fructose infusion.

Effects of a glucose meal on energy metabolism in patients with cirrhosis before and after liver transplantation.

HYPOTHESIS: Liver transplantation results in hepatic denervation. This may produce alterations of liver energy and substrate metabolism, which may contribute to weight gain after liver transplantation. DESIGN: Prospective clinical study. SETTING: Liver transplantation clinics in a university hospital. PATIENTS: Seven nondiabetic patients with cirrhosis were recruited while on a waiting list for liver transplantation. Seven healthy subjects were recruited as controls. INTERVENTION: Orthotopic liver transplantation. MAIN OUTCOME MEASURES: Evaluation of energy and substrate metabolism after ingestion of a glucose load with indirect calorimetry was performed before, 2 to 6 weeks after, and 5 to 19 months after transplantation. Whole-body glucose oxidation and storage and glucose-induced thermogenesis were calculated. RESULTS: Patients with cirrhosis had modestly elevated resting energy expenditure and normal glucose-induced thermogenesis and postprandial glucose oxidation and storage. These measures remained unchanged after liver transplantation despite a significant increase in postprandial glycemia. Patients, however, gained an average of 3 kg of body weight after 5 to 19 months compared with their weight before transplantation. CONCLUSION: Liver denervation secondary to transplantation does not lead to alterations of energy metabolism after ingestion of a glucose load.