Luzia Valentini

Malnutrition and impaired muscle strength in patients with Crohn's disease and ulcerative colitis in remission

OBJECTIVE This prospective, controlled, and multicentric study evaluated nutritional status, body composition, muscle strength, and quality of life in patients with inflammatory bowel disease in clinical remission. In addition, possible effects of gender, malnutrition, inflammation, and previous prednisolone therapy were investigated. METHODS Nutritional status (subjective global assessment [SGA], body mass index, albumin, trace elements), body composition (bioelectrical impedance analysis, anthropometry), handgrip strength, and quality of life were assessed in 94 patients with Crohns disease (CD; 61 female and 33 male, Crohns Disease Activity Index 71 +/- 47), 50 patients with ulcerative colitis (UC; 33 female and 17 male, Ulcerative Colitis Activity Index 3.1 +/- 1.5), and 61 healthy control subjects (41 female and 20 male) from centers in Berlin, Vienna, and Bari. For further analysis of body composition, 47 well-nourished patients with inflammatory bowel disease were pair-matched by body mass index, sex, and age to healthy controls. Data are presented as median (25th-75th percentile). RESULTS Most patients with inflammatory bowel disease (74%) were well nourished according to the SGA, body mass index, and serum albumin. However, body composition analysis demonstrated a decrease in body cell mass (BCM) in patients with CD (23.1 kg, 20.8-28.7, P = 0.021) and UC (22.6 kg, 21.0-28.0, P = 0.041) compared with controls (25.0 kg, 22.0-32.5). Handgrip strength correlated with BCM (r = 0.703, P = 0.001) and was decreased in patients with CD (32.8 kg, 26.0-41.1, P = 0.005) and UC (31.0 kg, 27.3-37.8, P = 0.001) compared with controls (36.0 kg, 31.0-52.0). The alterations were seen even in patients classified as well nourished. BCM was lower in patients with moderately increased serum C-reactive protein levels compared with patients with normal levels. CONCLUSION In CD and UC, selected micronutrient deficits and loss of BCM and muscle strength are frequent in remission and cannot be detected by standard malnutrition screening.

Circulating adipokines and the protective effects of hyperinsulinemia in inflammatory bowel disease.

OBJECTIVE Adipokines are fat-derived hormones and cytokines with immune-modulating and metabolic properties. Most of them are associated with insulin resistance. The aim of the present investigation was to evaluate circulating levels of adipokines and glucose homeostasis in patients with inflammatory bowel disease (IBD) and to evaluate possible associations with the course and characteristics of the disease. METHODS Serum leptin, resistin, visfatin, retinol-binding protein-4, adiponectin, glucose, insulin, and inflammatory parameters were analyzed in 93 patients with inactive IBD (49 with Crohns disease [CD], 44 with ulcerative colitis [UC]), 35 patients with active IBD (18 with CD, 17 with UC), and 37 age- and body mass index-matched healthy controls. Ninety-two patients were followed for 6 mo. RESULTS Leptin was similar in patients with IBD and controls, whereas resistin and visfatin were increased in patients with active disease but not in those in remission. In active and inactive disease, adiponectin was decreased (P < 0.001) and retinol-binding protein-4 was increased (P < 0.001) compared with controls. About 60% of patients with IBD showed increased levels of insulin, whereas serum glucose remained normal, resulting in increased homeostasis model assessment values in most patients. Hyperinsulinemia was associated with the decrease in adiponectin (r = -0.572, P < 0.001) and proved to be an independent protective factor for 6-mo maintenance of remission (P = 0.016). CONCLUSION IBD led to largely similar alterations in circulating adipokines and hyperinsulinemia in patients with CD and those with UC. The unexpected protective effect of hyperinsulinemia on relapse rate denotes the role of the metabolic-inflammatory response as a modulator in IBD.

The first nutritionDay in nursing homes: Participation may improve malnutrition awareness ☆

BACKGROUND & AIMS A modified version of the nutritionDay project was developed for nursing homes (NHs) to increase malnutrition awareness in this area. This report aims to describe the first results from the NH setting. METHODS On February 22, 2007, 8 Austrian and 30 German NHs with a total of 79 units and 2137 residents (84+/-9 years of age, 79% female) participated in the NH-adapted pilot test. The NHs participated voluntarily using standardized questionnaires. The actual nutritional intake at lunch time was documented for each resident. Six-month follow-up data were received from 1483 residents (69%). RESULTS Overall, 9.2% and 16.7% of residents were classified as malnourished subjectively by NH staff and by BMI criteria (<20 kg/m(2)), respectively. Independent risk factors for malnutrition included age>90 years, immobility, dementia, and dysphagia (all p<0.001). In total, 89% of residents ate at least half of the lunch meal, and 46% of residents received eating assistance for an average of 15 min. Six-month mortality was higher in residents with low nutritionDay BMI (<20 kg/m(2): 22%, 20-21.9 kg/m(2): 17%) compared to residents with BMI >or= 22 kg/m(2) (10%, p<0.001). Six-month weight loss >or= 6 kg was less common in residents with nutritionDay BMI<22 kg/m(2) compared to residents with higher nutritionDay BMI (3.4% vs 12.4%, p<0.001). CONCLUSIONS The first nutritionDay in NH provided valuable data on the nutritional status of NH residents and called attention to the remarkable time investment required by NH staff to adequately provide eating assistance to residents. Participation in the nutritionDay project appears to increase malnutrition awareness as reflected in the outcome weight results.

Determinants of hand grip strength, knee extension strength and functional status in cancer patients

BACKGROUND & AIMS Decreased functionality and muscle weakness are prominent features in cancer patients. We investigated determinants of muscle function assessed by hand grip and knee extension strength as well as functional status in cancer patients. METHODS 189 consecutively admitted cancer patients (age 60.8 ± 12.7 years, 96 male) were recruited. Muscle function was assessed by hand grip and knee extension strength, and percentage of anticipated peak expiratory flow (%PEF). Functional status was determined by the EORTC questionnaire of quality of life. Nutritional status was assessed with Subjective Global Assessment (SGA). Age, gender, SGA, body mass index, clinical variables such as cancer location, presence of distant metastases, tumour burden according to TNM stage, UICC stage, number of drugs per day, number of comorbidities, type of treatment and depression were investigated as potential risk factors for muscle weakness and impaired functional status in a multiple regression analysis. RESULTS 80 patients (39 male) were classified moderately or severely malnourished. Malnutrition also emerged as an independent determinant for hand grip (estimated effect size 11%, p < 0.01), knee extension strength (estimated effect size 12%, p < 0.001), and peak expiratory flow (estimated effect size 30%, p < 0.008) and functional status (estimated effect size 19.4%, p < 0.001) next to age and gender, which were the strongest predictors. Among the disease parameters, only amount of daily medication exhibited a significant influence on knee extension strength. CONCLUSIONS Malnutrition is a disease independent risk factor for reduced muscle strength and functional status in cancer patients. Treatment of malnutrition might therefore also restore muscle strength.

Determinants of bioelectrical phase angle in disease

Phase angle (PhA), a parameter of bioelectrical impedance analysis, is a well-known predictor of morbidity and mortality in various diseases. The causes of decreased PhA are, however, not yet completely understood. We therefore investigated determinants of PhA in 777 hospitalised patients in a retrospective analysis. PhA was assessed by bioelectrical impedance analysis at 50 KHz. Subjective global assessment (SGA) was used to evaluate nutritional status. Age, sex, BMI as well as nutritional status (SGA), benign or malignant disease and C-reactive protein (CRP) were investigated as potential determinants of PhA and standardised PhA (SPhA) = (observed PhA - mean PhA of reference values)/standard deviation of reference values in a general linear model regression analysis. Next to age (estimated effect size, 46·6%; P<0·0001), malnutrition (39·1%; P<0·0001) emerged as a major PhA determinant in our study population. Moreover, sex (6·4%; P<0·0001), CRP (4·4%; P<0·0001) and BMI (3·5%; P < 0·0001) exhibited a significant influence on PhA, whereas malignant disease showed no significant effect in this model. The only significant determinants of SPhA were malnutrition (85·4%; P<0·0001) and inflammation (9·6 %; P<0·0001). In conclusion, next to the established predictors, malnutrition and inflammation have a strong impact on PhA in sick individuals, which partly explains its prognostic power. When investigating the SPhA, only malnutrition and inflammation were found to be significant predictors, as a result of which the SPhA is considered a more suitable indicator of nutritional and health status.

Altered status of antioxidant vitamins and fatty acids in patients with inactive inflammatory bowel disease

BACKGROUND & AIMS Data regarding the nutritional status, antioxidant compounds and plasma fatty acid (FA) composition in inactive IBD are conflicting. We compared plasma levels of antioxidants and FA of patients with inactive IBD with active IBD and controls. METHODS Plasma levels of vitamin C, vitamin E, carotenoids, saturated, monounsaturated and polyunsaturated FA, inflammatory markers and nutritional status were determined after an overnight fast in 132 patients with quiescent IBD (40.6+/-13.2 years, 87F/45M), 35 patients with active disease (37.9+/-12.1 years, 25F/10M) and 45 age- and BMI-matched healthy controls (38.1+/-10.5 years, 39F/6M). Results are expressed as mean+/-SD or median [25th percentile;75th percentile]. RESULTS Body mass index (BMI) was normal in inactive (23.9+/-4.7 kg/m(2)), active IBD (22.7+/-4.2 kg/m(2)) and controls (22.3+/-1.9 kg/m(2)). Compared with controls patients with quiescent IBD showed significantly decreased plasma levels of carotenoids (1.85 [1.37;2.56] vs 1.39 [0.88;1.87] micromol/L) and vitamin C (62.3 [48.7;75.0] vs 51.0 [36.4;77.6] micromol/L), increased levels of saturated FA (3879 [3380;4420] vs 3410 [3142;3989] micromol/L) and monounsaturated FA (2578 [2258;3089] vs 2044 [1836;2434] micromol/L) and similar levels of vitamin E and polyunsaturated FA. Results in active disease were similar to inactive disease. CONCLUSION This study shows that antioxidant status and FA profile in a larger population of IBD patients are disturbed independently from disease activity and despite normal overall nutritional status.

Resistance of nitrogen metabolism to growth hormone treatment in the early phase after injury of patients with multiple injuries

OBJECTIVES AND DESIGN Several studies have shown an anticatabolic effect of recombinant human growth hormone (rhGH) in surgical patients. We investigated, in a prospective, randomized, double blind, and placebo-controlled study, the effect of r-hGH on hormone and nitrogen metabolism in 14 patients with multiple injuries in the early phase of injury. MATERIALS AND METHODS All patients were treated in the intensive care unit, had mechanical ventilation, and were highly catabolic, with a mean daily nitrogen loss of 13.2 +/- 1.8 g. r-hGH was given subcutaneously (once a day, at 8 PM) in a dosage of 0.2 IU/kg.d for seven days, starting on the second day after injury. RESULTS Administration of r-hGH evoked a significant increase in plasma concentrations of GH, insulin-like growth factor-I (IGF-I), and insulin-like growth factor binding-protein-3 (IGFBP-3). No significant differences were found for either daily or cumulative nitrogen balances (-103.1 +/- 14 g for patients receiving r-hGH and -92.1 +/- 18.1 for those with placebo). r-hGH therapy did not affect skeletal muscle extracellular water, nor did it affect plasma or muscle concentrations of total free amino acids or glutamine. Plasma albumin, prealbumin, and retinol-binding protein concentrations were also unchanged by r-hGH therapy, as were the urinary excretion of potassium and urea. CONCLUSIONS We conclude that elevated plasma levels of GH, insulin, and IGF-I are unable to effect a protein anabolic drive in patients with multiple injuries during the early postinjury phase and assume that this r-hGH resistance to nitrogen metabolism takes place at the level distal to IGF-I.

Plasma Bile Acids Are Associated with Energy Expenditure and Thyroid Function in Humans

BACKGROUND/AIMS Animal studies implicate a role of bile acids (BA) in thyroid-regulated energy expenditure (EE) via activation of the TGR-5/adenylate cyclase/deiodinase type 2 pathway. Here we investigated these possible associations in humans. METHODS EE, BA, and thyroid hormone status were assessed in 10 healthy subjects and eight patients with liver cirrhosis at baseline and after oral nutrition. In cirrhosis, blood was additionally sampled from the mesenteric vein and the radial artery. RESULTS At baseline, BA and EE related positively (r = 0.648, P = 0.048 in healthy subjects; r = 0.833, P = 0.010 in cirrhosis; r = 0.556, P =0.017 in all), with the highest correlation with deoxycholic acid levels. The respiratory quotient associated negatively to baseline BA (all, r = -0.639, P = 0.004). Postprandially, serum TSH decreased in both groups (P < 0.05 each). In cirrhosis, the decrease of TSH after 60 min correlated to the meal-stimulated BA increase (r = -0.762, P = 0.028). To assess the mechanism involved, we studied a single human TSHoma and TαT1 mouse thyrotrope cells. In TSHoma cells, TGR-5 was predominantly expressed cytoplasmically, and in vitro stimulation with BA did not substantially alter cAMP or deiodinase type 2. CONCLUSIONS Our data support a role of BA in human energy metabolism and in thyroid hormone control. Even though no convincing response to BA was demonstrated in TSHoma and TαT1 cells, the TSH decrease after a nutritional challenge suggests an interaction of BA on the set point of the thyroid axis.

Disease-related malnutrition but not underweight by BMI is reflected by disturbed electric tissue properties in the bioelectrical impedance vector analysis

The calculation of body composition using bioelectrical impedance analysis in sick and hospitalized patients is hampered due to altered hydration state. We wanted to investigate how disease-related malnutrition assessed by the Subjective Global Assessment (SGA) is reflected in the bioelectrical impedance vector analysis. Patients with benign gastrointestinal disease (n 242) were entered in the study. Nutritional status was assessed by SGA. Arm muscle and fat area were estimated by anthropometry, muscle function was determined by hand grip strength. Whole body impedance measurements were made at 50 kHz. Ninety-eight patients were considered well nourished (SGA A), ninety-four were classified moderately malnourished (SGA B) and fifty patients were classified severely malnourished (SGA C) according to the SGA. The mean vector was significantly displaced between SGA C and SGA A and B, showing comparable resistance with a significantly reduced reactance, indicating comparable hydration but loss of dielectrical mass of soft tissues. This distinctive vector migration was not seen when studying the patients grouped according to BMI. In conclusion, disease-related malnutrition as assessed by the SGA is associated with a distinctive bioelectrical vector migration, implying that abnormal tissue structure and not reduced body mass only occurs in disease-related malnutrition. These disturbances are not seen in underweight according to BMI. Bioelectrical impedance vector analysis appears to be an attractive tool to identify disease-related malnutrition and to monitor nutritional intervention.

Increased intestinal permeability in malnourished patients with liver cirrhosis

Background/objective:Malnutrition is a prominent feature in liver cirrhosis, with deleterious impact on clinical outcome. The objective of this study is to investigate whether malnutrition is associated with increased gastrointestinal permeability in liver cirrhosis reflected by altered urinary excretion of non-metabolizable sugar probes.Subjects/methods:Patients with advanced liver cirrhosis (Child Pugh Score B or C) were recruited. Nutritional status was determined according to the Subjective Global Assessment. Intestinal permeability was assessed by measuring the urinary excretion of orally administered, non-metabolized sugar probe molecules. The lactulose/mannitol ratio served as marker for intestinal permeability and reflects non-carrier-mediated transcellular and paracellular transport of the small intestine during the first 5 h. Sucrose recovery in urine within the first 5 h reflects gastroduodenal permeability; sucralose recovery in urine 5–26 h after consumption reflects colonic permeability.Results:Sixty-four patients (56.7±10.8 years; 33% female) were included in the study. Twenty-one patients were considered well nourished according to the Subjective Global Assessment, 23 moderately nourished and 20 patients severely malnourished; 74% had alcoholic liver disease and 67% had cirrhosis stage Child C. Gastroduodenal and colonic permeability was significantly increased in patients with liver cirrhosis compared with 63 healthy controls (0.23±0.22 and 1.37±1.42% vs 0.14±0.10 and 0.41±0.72% in controls), but not different between well and malnourished subjects. Small intestinal permeability (lactulose/mannitol ratio) was increased in all patients (0.069±0.055%) and further increased in malnourished patients (0.048±0.031% vs 0.084±0.061%, P=0.004) due to decreased mannitol recovery only.Conclusions:Gastric, small intestinal and even colonic permeability was altogether increased in liver cirrhosis, and malnutrition was associated with further increased small intestinal permeability indicative of villous atrophy.