Lumacaftor/ivacaftor in cystic fibrosis: effects on glucose metabolism and insulin secretion.

PURPOSE: The question whether the new cystic fibrosis transmembrane conductance regulator (CFTR) modulator drugs aimed at restoring CFTR protein function might improve glucose metabolism is gaining attention, but data on the effect of lumacaftor/ivacaftor treatment (LUMA/IVA) on glucose tolerance are limited. We evaluated the variation in glucose metabolism and insulin secretion in CF patients homozygous for Phe508del CFTR mutation after one-year treatment with LUMA/IVA in comparison to patients with the same genotype who did not receive such treatment. METHODS: We performed a retrospective case-control study on 13 patients with a confirmed diagnosis of CF, homozygous for the Phe508del CFTR mutation, who received LUMA/IVA for one year (cases) and 13 patients with identical genotype who did not receive this treatment (controls). At the beginning and conclusion of the follow-up, all subjects received a modified 3 h OGTT, sampling at baseline, and at 30 min intervals for plasma glucose, serum insulin, and c-peptide concentrations to evaluate glucose tolerance, and quantify by modeling beta-cell insulin secretion responsiveness to glucose, insulin clearance and insulin sensitivity. RESULTS: LUMA/IVA did not produce differences in glucose tolerance, insulin secretory parameters, clearance and sensitivity with respect to matched controls over one-year follow-up. CONCLUSION: We found no evidence of improvements in glucose tolerance mechanisms in patients with CF after one-year treatment with LUMA/IVA.

Association between ratio indexes of body composition phenotypes and metabolic risk in Italian adults.

The ratio between fat mass (FM) and fat-free mass (FFM) has been used to discriminate individual differences in body composition and improve prediction of metabolic risk. Here, we evaluated whether the use of a visceral adipose tissue-to-fat-free mass index (VAT:FFMI) ratio was a better predictor of metabolic risk than a fat mass index to fat-free mass index (FMI:FFMI) ratio. This is a cross-sectional study including 3441 adult participants (age range 18-81; men/women: 977/2464). FM and FFM were measured by bioelectrical impedance analysis and VAT by ultrasonography. A continuous metabolic risk Z score and harmonised international criteria were used to define cumulative metabolic risk and metabolic syndrome (MetS), respectively. Multivariate logistic and linear regression models were used to test associations between body composition indexes and metabolic risk. In unadjusted models, VAT:FFMI was a better predictor of MetS (OR 8.03, 95%CI 6.69-9.65) compared to FMI:FFMI (OR 2.91, 95%CI 2.45-3.46). However, the strength of association of VAT:FFMI and FMI:FFMI became comparable when models were adjusted for age, gender, clinical and sociodemographic factors (OR 4.06, 95%CI 3.31-4.97; OR 4.25, 95%CI 3.42-5.27, respectively). A similar pattern was observed for the association of the two indexes with the metabolic risk Z score (VAT:FFMI: unadjusted b = 0.69 ± 0.03, adjusted b = 0.36 ± 0.03; FMI:FFMI: unadjusted b = 0.28 ± 0.028, adjusted b = 0.38 ± 0.02). Our results suggest that there is no real advantage in using either VAT:FFMI or FMI:FFMI ratios as a predictor of metabolic risk in adults. However, these results warrant confirmation in longitudinal studies.

Accuracy of predictive equations for the measurement of resting energy expenditure in older subjects.

BACKGROUND AND AIMS: The measurement of resting energy expenditure (REE) is important to assess individual total energy requirements in older subjects. The validity of REE prediction equations in this population has not been thoroughly evaluated and therefore the main aim of this analysis was to assess the accuracy of REE prediction equations in older subjects. METHODS: Weight, height and body mass index (BMI) were measured. REE was measured by indirect calorimetry (IC) in 68 older subjects (age: 60-94 years, M/F: 13/55, BMI: 26.3 ± 5.0 kg/m(2)). Measured REE was compared to 14 equations for the calculation of REE estimates. In addition, two novel approaches (Aggregate model and meta-regression equations) for the prediction of REE were evaluated. Paired t test and Bland-Altman method were used to assess the agreement of the equations. RESULTS: The average measured REE was 1298 ± 264 kcal/day. The equation with the smallest bias was proposed by Muller (Bias ± 2SD = +3 ± 294 kcal/day) whereas the Mifflin equation was associated with the largest error (Bias ± 2SD = -172 ± 282 kcal/day). The Aggregate, Muller, Harris-Benedict and Fredrix equations were characterised by a prediction within ±10% of measured REE in more than 60% of subjects. Of the four algorithms, only the Aggregate equation did not show a significant association of the measurement bias with age, BMI and gender. CONCLUSIONS: The Aggregate algorithm was characterised by a higher, overall accuracy for the prediction of REE in older subjects and its use should be advocated in older subjects. However, due to the large variability of the estimates, the measurement of REE by IC is still recommended for an accurate assessment of individual REE.

Accuracy of three novel predictive methods for measurements of fat mass in healthy older subjects.

UNLABELLED: This study evaluated the agreement of novel anthropometric equations and established indirect methods (skinfold thickness and bioimpedance analysis) with reference methods [dual X-ray absorptiometry (DXA) and air displacement plethysmography (ADP)] for fat mass assessment (FM) in older subjects. METHODS: Forty subjects (M/F = 15/25, age = 61-84 years, BMI = 18-37 kg/m(2)) were recruited. The agreement of the following predictive equations was evaluated: body adiposity index (BAI), BAI-Fels and Clínica Universidad de Navarra-body adiposity estimator (CUN-BAE). RESULTS: BAI estimates were comparable to DXA (Δ ± 2SD = 0.4 ± 6.0 kg, p > 0.05) but not to ADP (Δ ± 2SD = -2.8 ± 7.2 kg, p < 0.001); BAI-Fels estimates were comparable to DXA (Δ ± 2SD = 0.8 ± 5.5 kg, p > 0.05) but not to ADP (Δ ± 2SD = -4.0 ± 6.9 kg, p < 0.001). The difference between CUN-BAE and ADP was not significant (Δ ± 2SD = -0.4 ± 5.6 kg, p > 0.05), whereas it significantly overestimated DXA (Δ ± 2SD = 2.8 ± 5.4 kg, p < 0.001). ADP significantly overestimated FM compared to DXA (Δ ± 2SD = 3.2 ± 5.4 kg, p < 0.001) and the measurement bias was significantly correlated with BMI in men (p = 0.004). CONCLUSIONS: The accuracy of the three anthropometric indexes is dependent on the choice of the reference method. The variability of the FM estimates was large and these indexes cannot be recommended for the assessment of FM in older subjects.

Identification of insulin secretory defects and insulin resistance during oral glucose tolerance test in a cohort of cystic fibrosis patients.

BACKGROUND: Cystic fibrosis (CF)-related diabetes is a leading complication of CF and is associated with pulmonary and nutritional deterioration, years before an evident hyperglycemia, possibly because of insulin deficiency and resistance. AIM: To evaluate glucose tolerance, insulin secretion, and insulin sensitivity by a widely applicable method suitable for accurate and prospective measurements in a CF population. METHODS: A total of 165 CF subjects (80 females) aged 17±5 years and 18 age- and sex-matched healthy controls (CON) received an oral glucose tolerance test with glucose, insulin and C-peptide determinations. Insulin sensitivity was defined on the basis of glucose and insulin concentrations using the oral glucose insulin sensitivity index, whereas ß-cell function was determined on the basis of a model relating insulin secretion (C-peptide profile) to glucose concentration. RESULTS: Fifteen percent of CF patients had glucose intolerance and 6% had diabetes without fasting hyperglycemia and 3% had diabetes with fasting hyperglycemia. ß-cell function was reduced in CF patients compared with CON (70.0±4.1 vs 117.9±11.6  pmol/min per m(2) per mM, P<0.001) and decreased significantly with age by -2.7  pmol/min per m(2) per mM per year (confidence interval (CI) -4.5 to -0.82), i.e. almost 4% yearly. The early insulin secretion index was also reduced. Insulin sensitivity was similar to CON. CF patients who attained glucose tolerance comparable to CON had lower ß-cell function and higher insulin sensitivity. CONCLUSION: The major alteration in insulin secretion and insulin sensitivity of CF patients is slowly declining ß-cell function, consisting of delayed and reduced responsiveness to hyperglycemia, that in CF patients with normal glucose tolerance may be compensated by an increased insulin sensitivity.

Estimated height from knee-height in Caucasian elderly: implications on nutritional status by mini nutritional assessment.

OBJECTIVES: To investigate if the use of estimated height (EH) by currently available prediction formulas might affect the screening and outcome prediction attitudes of both the Mini Nutritional Assessment (MNA) and its short-form version (MNA-SF). DESIGN: A 6-month observational study. SETTING: Two long-term cares of the province of Como. PARTICIPANTS: 266 resident elderly (102 men, 164 women; mean age +/- SD: 80.4 +/- 8.6 years). MEASUREMENTS: Subjects were studied by anthropometry (weight, standing height, knee-height, arm and calf circumferences, triceps skinfold) and biochemistry (albumin and prealbumin). Nutritional status was assessed using both MNA and MNA-SF. At 6 months, major outcome were: death, infections and bedsores. RESULTS: In overall population, prediction formulas significantly underestimated real height. The bias by Italian-specific equation was higher than that by nationally-representative formulas for white Americans. The use of EHs produced significant differences in body mass index (BMI) but these did not affect nutritional status scoring by MNA and MNA-SF (r > or =0.99, p < 0.0001). Cohen's kappa statistic also showed an almost perfect concordance (kappa > 0.9). Moreover, similar degrees of correlation were found between nutritional parameters and both MNA and MNA-SF scores by BMI from SH and EHs. After 6 months, major complications occurred in twenty-eight patients (11.6%). The use EHs did not affect the distribution of events among MNA and MNA-SF nutritional classes. CONCLUSION: In Italian elderly, height prediction by nationally representative equations for white Americans should be preferred to that by ethnic-specifc formula. However, the use of both models does not seem to affect nutritional screening and outcome prediction by MNA and MNA-SF.

Protein and glutamine kinetics during counter-regulatory failure in type 1 diabetes.

BACKGROUND AND AIMS: Healthy individuals counteract insulin-induced hypoglycaemia by increasing glutamine utilization but not proteolysis. Glucagon is important to this response because it increases glutamine uptake. In type 1 diabetes (T1DM) glucagon and epinephrine responses to hypoglycaemia are defective. We investigated whether glutamine and amino acid utilization during hypoglycaemia is altered in T1DM with defective counter-regulatory responses. METHODS AND RESULTS: Eight T1DM patients (duration of diabetes 14+/-4 years and therefore with presumed defective counter-regulatory response) and eight controls (CON) received a 3h hypoglycaemic hyperinsulinaemic (0.65mU/kg per min) clamp coupled to [6,6-(2)H(2)]glucose, [1-(13)C]leucine and [2-(15)N]glutamine to trace the relative kinetics. Post-absorptive plasma glucose and glucose uptake were increased in T1DM (9.09+/-0.99 vs 5.01+/-0.22mmol/l and 19.5+/-0.9 vs 12.6+/-0.8micromol/kg per min, p<0.01). During the clamp T1DM but not CON required exogenous glucose (4.4+/-1.7micromol/kg per min) to maintain the hypoglycaemic plateau because the endogenous glucose production was significantly suppressed (p<0.01). In T1DM the leucine and phenylalanine concentrations were less suppressed from basal (p<0.05) despite a similar insulin suppression of proteolysis (-16+/-2 vs -20+/-4%, p=ns) indicating a defective stimulation of leucine metabolic clearance from basal (+18+/-3% vs +55+/-9%, p<0.01). Glutamine concentration remained unchanged from basal (-7+/-3% vs -35+/-3%, p<0.01) and the clearance of glutamine was markedly defective in T1DM (+6+/-2%) in comparison with controls (+22+/-4%; p=0.02). CONCLUSIONS: In T1DM, the counter-regulatory failure to hypoglycaemia seems to be associated with a defective glutamine utilization. The failure to clear circulating amino acids, specifically glutamine, during hypoglycaemia may adversely affect gluconeogenesis.

Nutritional counselling in disabled people: effects on dietary patterns, body composition and cardiovascular risk factors.

AIM: Disabled persons are frequently affected by nutritional status impairment, consequent to quantitative and qualitative inadequacy of diet and physical inactivity, resulting in a significant reduction of fat-free mass and bone mineral density (BMD), and an over-expression of fat mass and an increased number of biochemical risk factors for chronic degenerative diseases. The aim of this study was to analyse the applicability and the efficacy of a nutritional counselling intervention in order to improve dietary intake and nutritional status in disabled people. METHODS: Thirty-seven disabled subjects (24 with physical disability and 13 with both mental retardation and physical disability; age 33.5+/-9.2 years) underwent an assessment of nutritional status, and an intervention with nutritional counselling was proposed to each patient for one year. Anthropometric measurements, indirect calorimetry, dual-energy X-ray absorptiometry, dietary intake, and biochemical analysis at baseline (T0) and after one year (T1) of counselling intervention were performed. RESULTS: Sixty-five percent of patients dropped out. Overall, no significant improvement in cardiovascular risk factors, body composition and dietary patterns was reported at T1 in completer subjects. Six subjects who were obese or overweight at T0, reported significant weight and fat mass (FM) reduction at T1 (P=0.01 and P=0.00, respectively). CONCLUSION: Nutritional counselling seems to be ineffective and poorly applicable to disabled people. Further studies should be directed towards a treatment program associated with careful screening, motivation analysis, and follow-up in this patient population.

Poor agreement between a portable armband and indirect calorimetry in the assessment of resting energy expenditure.

BACKGROUND & AIMS: To evaluate the agreement between resting energy expenditure (REE) estimated by a portable armband and measured by indirect calorimetry. METHODS: One-hundred and twenty-seven women and 42 men with a mean (SD) age of 44 (12) years and a body mass index of 30.2 (5.4) kg/m(2) were studied. REE was estimated using the Sense Wear Pro 2 Armband (SWA), measured using the Sensor Medics 29 metabolic cart (V(max)), and estimated using Schofield's equation. The limits of agreement (LOA) and the concordance correlation coefficient (CCC) were used to evaluate the interchangeability of the methods. RESULTS: The LOA between REE(SWA) and REE(Vmax) were wide in both women (-269 to 378 kcal/day) and men (-330 to 545 kcal/day) and CCC was low (0.579 in females and 0.583 in males, p<0.0001 for both). REE(Schofield) agreed with REE(Vmax) to a similar degree (CCC=0.563 in females and 0.500 in males, p<0.0001 for both). CONCLUSIONS: SWA and indirect calorimetry are not interchangeable methods for the assessment of REE in normal-weight and obese subjects.

Evaluation of air-displacement plethysmography and bioelectrical impedance analysis vs dual-energy X-ray absorptiometry for the assessment of fat-free mass in elderly subjects.

OBJECTIVE: To evaluate air-displacement plethysmography (ADP) and bioelectrical impedance analysis (BIA) vs dual-energy X-ray absorptiometry (DXA) for the assessment of fat-free mass (FFM) in healthy elderly subjects. SUBJECTS: Forty-two women and twenty-six men aged 60-84 years. METHODS: FFM was measured by DXA and ADP. Body impedance (Z) was measured by four-polar BIA and the impedance index (ZI) was calculated as stature(2)/Z. Selection of predictors (gender, age, weight and ZI at 5, 50 and 100 kHz) for BIA algorithms was carried out using bootstrapped stepwise linear regression on 1000 samples of 68 subjects. Limits of agreement were used as measures of interchangeability of ADP and BIA with DXA. RESULTS: The limits of agreement of ADP vs DXA were -11.0 to 2.4 kg in males and -4.8 to 2.2 kg in females. Gender, weight and ZI(100) were selected as predictors of FFM by bootstrapped stepwise linear regression. In males, ZI(100) (-12.2 to 12.2 kg) was much less accurate than weight (-6.0 to 6.0 kg) at predicting FFM and their combination did not improve the estimate (-6.0 to 6.0 kg). In females, ZI(100) (-6.8 to 6.8 kg) was less accurate than weight (-5.6 to 5.6 kg) at predicting FFM and their combination improved the estimate only slightly (-5.0 to 5.0 kg). CONCLUSIONS: In healthy elderly subjects, (1) ADP and DXA are not interchangeable for the assessment of FFM, especially in males; and (2) ZI(100) is not superior to weight for the prediction of FFM and their combination is of little advantage and only in females.

Atrial natriuretic peptide in diabetic and nondiabetic patients with and without heart transplantation.

BACKGROUND: Natriuretic peptides are useful markers for risk stratification of patients with heart disease. However, conflicting results have been reported about circulating atrial natriuretic peptide (ANP) concentration in heart transplant recipients. METHODS: To ascertain the effects of diabetes and acute insulin administration on plasma ANP concentrations in a model of heart denervation, we studied 12 diabetic (D-OHT) and 6 nondiabetic heart-transplanted (OHT) patients using the euglycemic-hyperinsulinemic clamp and oral glucose tolerance tests. Five patients with type 2 diabetes without heart transplantation (D) and 9 healthy subjects (NOR) matched for anthropometric features served as the controls. RESULTS: Means baseline plasma ANP concentration was higher in D-OHT (82 +/- 15 pg/mL) than in OHT or NOR (27 +/- 4 or 30 +/- 5; P < .01), but was not different than D (69 +/- 12; P = .82). During the clamp plasma ANP showed similar increases in all groups (49 +/- 4, 39 +/- 3, 59 +/- 4, and 49 +/- 3% in D-OHT, OHT, D, and NOR; P < .02 vs basal, P = NS among groups). Plasma osmolarity and catecholamines were also not different among groups and did not increase during the clamp. Fasting plasma ANP concentrations correlated with plasma glucose concentrations measured 120 minutes after oral glucose tolerance testing. CONCLUSIONS: Among heart transplantation recipients fasting plasma ANP concentrations were not different at 5 to 6 years after the surgical procedure than in nondiabetic controls. Increased ANP concentrations were observed among recipients with diabetes and among nontransplanted diabetic patients. Although the insulin-induced increment in ANP concentrations was not different among groups, circulating ANP was strongly associated with glucose tolerance status.

Circulating salicylic acid is related to fruit and vegetable consumption in healthy subjects.

Salicylic acid (SA) is a natural phenolic compound known as the active principle of aspirin. Its presence in vegetal sources suggests that fruit and vegetable (FV) consumption could produce measurable SA serum concentrations in human subjects not taking aspirin. The aim of this study was to investigate the relationship between FV intake and circulating SA in healthy subjects. Thirty-eight volunteers (twenty-two males and sixteen females) were recruited from an Italian university campus. They recorded their food intake for 7 d to evaluate dietary consumption and, in particular, FV intake; fasting blood samples were taken on the morning of the eighth day to measure SA serum concentration, using a sensitive stable isotope dilution and GC-MS method. Median SA serum concentration was 0.124 mumol/l (range 0.028-0.295). Circulating SA was significantly related to FV consumption, both to the mean daily intake (r2 0.13, P = 0.03) and to the last day intake (r2 0.16, P = 0.01). The subjects in the highest FV intake quartile in the preceding day (>4.75 servings) had significantly higher SA concentrations than in the lowest quartile ( < 2.3 servings) (median concentrations 0.188 and 0.112 mumol/l, respectively; P = 0.04). This study proved that, after overnight fast, human subjects not taking aspirin display circulating SA in amounts related to the FV consumption. It is therefore possible that the beneficial effects of regular FV consumption in man could also depend on low chronic SA exposure.

Spontaneous hypoglycemia in patients with cystic fibrosis.

OBJECTIVE: Diabetes frequently complicates cystic fibrosis (CF) without fasting hyperglycemia or despite spontaneous hypoglycemia (anecdotally ascribed to malnutrition), whose prevalence, clinical meaning, and relationship with glucose tolerance and clinical/nutritional status were not previously investigated. The relationship of CF genotype with insulin secretion control is also unclear. DESIGN AND METHODS: A total of 129 CF patients without stable diabetes received 188 oral glucose tolerance tests. Distribution of fasting plasma glucose (FPG), glucose, insulin and C-peptide responses, clinical/nutritional variables, and their relationships were analyzed. RESULTS: FPG < 60 mg/dl (3.3 mmo/l) was detected in 14% of studies and reactive hypoglycemia (PG < 50 mg/dl (2.8 mmo/l)) in 15%. OGTT-based diabetes frequency was similar in the lowest quartile (Q1) and Q2-3 for FPG (10 and 8%), with higher glucose increment and area under the curve in Q1. Insulin and C-peptide levels were similar among FPG quartiles. Class I cystic fibrosis transmembrane conductance regulator mutation carriers had higher insulin concentrations than class II, especially in Q1 for FPG. Age, sex, nutritional, and anthropometric parameters including fat and lean body mass were unrelated to FPG. Lower FPG was associated with more frequent hospitalization rates (P = 0.002) and lower Shwachman scores (P = 0.041). Steroids weaning was accurately evaluated but then excluded as a possible cause of hypoglycemia. CONCLUSIONS/INTERPRETATION: Fasting asymptomatic hypoglycemia is frequent and possibly related to inappropriate insulin secretion control in class I mutation carriers. Low FPG does not exclude impaired glucose tolerance (IGT) and diabetes in CF and reflects worse clinical status.

Is ghrelin a signal of decreased fat-free mass in elderly subjects?

OBJECTIVE: Aging is associated with appetite decline, weight loss, reduced fat-free mass (FFM), and increased fat mass (FM). Ghrelin and leptin are short- and long-term determinants of energy balance respectively, whose dysregulation could alter food intake. We evaluate the relationship of circulating ghrelin and leptin responses to standardized oral mixed nutrient load (SOMNL) with body composition, daily food intake, and insulin sensitivity in healthy elderly subjects (ES). DESIGN AND METHODS: Twenty-six ES (12/14 M/F, 69+/-4 years) and ten young healthy controls (LY) (5/5 M/F, 27+/-3 years) were studied at the International Center for the Assessment of Nutritional Status (Milan, Italy) with air plethysmography, dual energy X-ray absorptiometry, indirect calorimetry, and dietary intake assessment. Basal and postprandial ghrelin, leptin, testosterone, glucose, insulin and C-peptide concentrations, and insulin resistance (homeostasis model assessment (HOMA-R)) and sensitivity (quantitative insulin-sensitivity check index (QUICKI)) were evaluated. RESULTS: Basal ghrelin levels were similar in ES and LY, whereas leptin was higher in ES than LY, in agreement with the higher amount of FM. Basal and percentage change in ghrelin were inversely related to FFM, appendicular skeletal muscle mass (SMM), and QUICKI, but not to FM. Basal and percentage change in leptin were directly related to FM and not to FFM indexes. Ghrelin basal concentration was negatively correlated with energy and protein intake and with QUICKI. Percentage change in Ghrelin after SOMNL correlated negatively with protein intake, but positively with resting energy expenditure and energy intake, and glucose, insulin, C-peptide basal concentrations, and HOMA-R. CONCLUSION: In ES, basal and postprandial ghrelin increases with FFM, specifically SMM, reduction, whereas leptin increases with relative FM increases.

Measurement of salicylic acid in human serum using stable isotope dilution and gas chromatography-mass spectrometry.

A simple, highly selective, and sensitive method using stable isotope dilution and gas chromatography-mass spectrometry has been developed to quantify salicylic acid (SA) at concentrations naturally occurring in biological fluids, such as in the serum of subjects not taking aspirin. After extraction of liquid-liquid with diethyl ether and ethyl acetate and preparation of the tert-butyldimethylsilyl derivative, SA content was detected using deuterated SA as internal standard. The mean recovery of SA from serum was 85 +/- 6%. Intra- and interday precision and % relative error were <15% in all cases. With a detection limit of 0.6 ng and a quantification limit of 2 ng, the method is therefore also adequate for population studies because of the small amount of blood necessary to perform the analyses.

Nutritional status and dietary patterns in disabled people.

BACKGROUND AND AIM: Obesity, cardiovascular diseases, diabetes and osteoporosis are the most frequent pathologies among people with a severe reduction of physical activity. The impairment in nutritional status, consequent to quantitative and qualitative inadequacy of diet, could be one of the first steps in the development of co-morbidities in disabled subjects. In order to evaluate this hypothesis we investigated the nutritional status and the food intake in patients with physical or mental disabilities. METHODS AND RESULTS: Thirty-seven disabled subjects (24 with exclusively physical inactivity and 13 with mental retardation and physical inactivity) mean age 33.5+/-9.2 years and 25 healthy subjects (mean age 31.0+/-9.3 years) were enrolled. Anthropometric measurements, indirect calorimetry, dual-energy X-ray absorptiometry, dietary intake and biochemical parameters were collected for each subject. Forty percent of disabled were overweight and 14% were obese. Fat free mass (FFM) and bone mineral content (BMC) was lower and fat mass (FM) was higher than able-bodied control. Absolute resting energy expenditure (REE) was lower in disabled subjects, but this difference disappeared when REE was normalized to FFM. Dietary intake resulted unbalanced (16%, 31%, 50% of total daily energy intake derived from protein, lipid and carbohydrate respectively) with a distribution of dietary fatty acid quite far from the recommended ratio [3.1(SFA):4.1(MUFA):1.0(PUFA)] and an excessive consumption of simple carbohydrates (mean intake 17.5+/-4.9%). Insufficient intake of fibre, iron, calcium, potassium and zinc was also found. Finally, alterations in the cholesterol profile were evident in more than one third of the disabled subjects, whereas fasting glucose intolerance was evident in one fourth. CONCLUSION: This study shows a consistent nutritional status impairment in disabled patients resulting in an reduction of FFM and BMC, in an over-representation of FM and in a number of biochemical risk factors for cardiovascular disease. The altered nutritional status is counterparted by a widespread inadequacy of dietary patterns. This nutritional and dietary impairment occurs both in subjects with mental and physical diseases.

Time course of total and distrectual weight gain after refeeding in anorexia nervosa.

Anorectic patients who achieve complete recovery from the eating disorder can obtain a favorable psychosocial outcome but the long-term nutritional outcome is ill-defined. We investigated the time course of total and distrectual body composition during and after refeeding in 32 female patients with anorexia nervosa. Patients were enrolled at their lowest weight (T0) and re-examinated after a 15% weight gain (at a mean of 3 months, T1; n=17) and after 3 years of stable weight recovery (T2; n=8). At T2 patients were compared to a control group of 8 healthy females matched for age and body mass index. All subjects underwent dual X-ray absorptiometry and anthropometry at each visit. At T0, the 32 subjects were at 61%+/-8% of ideal body weight (IBW) with severe reductions in fat mass (FM; 7.1%+/-4.5%), fat free mass (FFM) and bone mineral content (BMC). At T2, the 8 subjects had gained 40% of initial weight, but remained at 85.1%+/-7.7% of IBW ( p<0.01 vs. controls), with a percent FM comparable to that of controls and an absolute FFM still deficient. BMC did not improve at T2 and remained 79% of that in controls. FM depletion was more severe in the limbs than in the trunk and at T2 the trunk/limb FM ratio remained greater than that in controls. These data strongly suggest that continued nutritional surveillance and support is necessary throughout these patients' lives, even after correction of the psychiatric illness and of severe underweight.

Feasibility of air plethysmography (BOD POD) in morbid obesity: a pilot study.

The assessment of body composition (BC) in morbidly obese patients is a difficult procedure. Air-displacement plethysmography (ADP), which measures body density, is a very promising technique for BC assessment in health and disease. However, there are very few data about the feasibility of applying ADP on morbidly obese patients, which theoretically could be affected by large body size and difficulty in lung volume measurements. The main aim of this pilot study was to evaluate the feasibility of using ADP for BC assessment in morbidly obese patients. We studied nine subjects (6 males and 3 females) who had a mean age (+/-SD) of 47.0+/-13.5 years and body mass index (BMI) of 46.6+/-7.7 kg/m(2) (range 36.4-58.8). All patients could fit into the instrument chamber and perform the manoeuvre for pulmonary plethysmography. Mean lung volume was 3.9+/-1.2 l and mean percent body fat was 53.1+/-6.6 (range 46.0-67.5). These results indicate that ADP appears to be suitable for patients with BMI over 40 kg/m(2) and produces realistic BC data.

Body composition assessment: an indispensable tool for disease management.

Recent conceptual and technology advancements fostered a rapid development in the field of body composition assessment and provided new and powerful investigative tools. Densitometry, isotopic dilution, bioelectrical impedance, whole-body counting, neutron activation, X-ray absorptiometry, computed tomography, magnetic resonance imaging, and spectroscopy have been the most widely employed methods. The result of this effort is the discovery that body composition at both molecular and cellular or tissue levels is affected by virtually all the pathologic conditions found in medical textbooks. The field is now mature for the clinical translation of this research. Some applications rely on a very solid base and their clinical use has been fully codified. Others still need reference values diversified on a regional and ethnic scale, consensus for interpretation of values, and guidelines for clinical indications. Only after these requirements are satisfied will it be possible to adopt specific practical guidelines, the most reasonable basis for acceptance and accreditation by care providers. Some applications are already being used in several settings. Therefore, establishing the guidelines for clinical application of body composition assessment methods is not only important for physicians and their patients, but is also urgent so as to prevent misuse and to ensure correct communication with the media in this field.

Indirect calorimetry and nutritional problems in clinical practice.

Indirect calorimetry is a simple and affordable tool for measuring energy expenditure and for quantifying the utilization of macronutrients. Its use is becoming increasingly widespread, but it is necessary to know its methodological features and its theoretical and practical limitations. Indirect calorimetry measures the rate of resting energy expenditure (REE), the major component of the total daily energy expenditure. Thus, indirect calorimetry reliably estimates the individual energy needs. Coupling the measurement of body composition to that of REE expands the diagnostic potential of indirect calorimetry. Once the lean and fat compartments have been measured, it is possible to establish on the basis of REE whether an individual is hyper- or hypometabolic. The evaluation of substrate oxidation by indirect calorimetry is subject to more severe theoretical constraints, because certain metabolic assumptions must be made. The clinical applications are practically unlimited. In the critically ill, a major goal is to maintain energy balance during the hypermetabolic response following trauma. The REE measurement is valuable from the diagnostic standpoint, because it recognizes discrepancies from the expected time-course of hypermetabolism, for example signaling a potentially catastrophic hypometabolic response. REE is also indispensable for providing correct nutritional support because both hyper- and undernutrition lead to increased mortality. In young or elderly patients, in whom energy consumption may be very different from that predicted from equations based on anthropometric measures, indirect calorimetry is particularly useful.