Determinants of weight, psychological status, food contemplation and lifestyle changes in patients with obesity during the COVID-19 lockdown: a nationwide survey using multiple correspondence analysis.

INTRODUCTION: The corona virus disease 2019 (COVID-19) pandemic forced most of the Italian population into lockdown from 11 March to 18 May 2020. A nationwide survey of Italian Clinical Nutrition and Dietetic Services (Obesity Centers or OCs) was carried out to assess the impact of lockdown restrictions on the physical and mental wellbeing of patients with obesity (PWO) who had follow-up appointments postponed due to lockdown restrictions and to compare determinants of weight gain before and after the pandemic. METHODS: We designed a structured 77-item questionnaire covering employment status, diet, physical activity and psychological aspects, that was disseminated through follow-up calls and online between 2 May and 25 June 2020. Data were analyzed by multiple correspondence analysis (MCA) and multiple linear regression. RESULTS: A total of 1,232 PWO from 26 OCs completed the questionnaires (72% female, mean age 50.2 ± 14.2 years; mean BMI 34.7 ± 7.6 kg/m2; 41% obesity class II to III). During the lockdown, 48.8% gained, 27.1% lost, while the remainder (24.1%) maintained their weight. The mean weight change was +2.3 ± 4.8 kg (in weight gainers: +4.0 ± 2.4 kg; +4.2% ± 5.4%). Approximately 37% of participants experienced increased emotional difficulties, mostly fear and dissatisfaction. Sixty-one percent reduced their physical activity (PA) and 55% experienced a change in sleep quality/quantity. The lack of online contact (37.5%) with the OC during lockdown strongly correlated with weight gain (p < 0.001). Using MCA, two main clusters were identified: those with unchanged or even improved lifestyles during lockdown (Cluster 1) and those with worse lifestyles during the same time (Cluster 2). The latter includes unemployed people experiencing depression, boredom, dissatisfaction and increased food contemplation and weight gain. Within Cluster 2, homemakers reported gaining weight and experiencing anger due to home confinement. CONCLUSIONS: Among Italian PWO, work status, emotional dysregulation, and lack of online communication with OCs were determinants of weight gain during the lockdown period.

Personality, attrition and weight loss in treatment seeking women with obesity.

Studies on small samples or in single units applying specific treatment programmes found an association between some personality traits and attrition and weight loss in individuals treated for obesity. We aimed to investigate whether pre-treatment personality traits were associated with weight loss outcomes in the general population of women with obesity. Attrition and weight loss outcomes after 12 months were measured in 634 women with obesity (mean age, 48; body mass index (BMI), 37.8 kg m(-2)) seeking treatment at eight Italian medical centres, applying different medical/cognitive behavioural programmes. Personality traits were assessed with the Temperament and Character Inventory (TCI), eating disorder features with the Binge Eating Scale (BES) and Night Eating Questionnaire (NEQ). Within the 12-month observation period, 32.3% of cases were lost to follow-up. After adjustment for demographic confounders and the severity of eating disorders, no TCI personality traits were significantly associated with attrition, while low scores of the novelty seeking temperament scale remained significantly associated with weight loss ≥ 10% (odds ratio, 0.983; 95% confidence interval, 0.975-0.992). Additional adjustment for education and job did not change the results. We conclude that personality does not systematically influence attrition in women with obesity enrolled into weight loss programmes in the community, whereas an association is maintained between novelty seeking and weight loss outcome. Studies adapting obesity interventions on the basis of individual novelty seeking scores might be warranted to maximize the results on body weight.

Rationale for hospital-based rehabilitation in obesity with comorbidities.

Severely obese patients affected by two or more chronic conditions which could mutually influence their outcome and disability can be defined as "complex" patients. The presence of multiple comorbidities often represents an obstacle for being admitted to clinical settings for the treatment of metabolic diseases. On the other hand, clinical Units with optimal standards for the treatment of pathological conditions in normal-weight patients are often structurally and technologically inadequate for the care of patients with extreme obesity. The aims of this review paper were to review the intrinsic (anthropometrics, body composition) and extrinsic (comorbidities) determinants of disability in obese patients and to provide an up-to-date definition of hospital-based multidisciplinary rehabilitation programs for severely obese patients with comorbidities. Rehabilitation of such patients require a here-and-now multidimensional, comprehensive approach, where the intensity of rehabilitative treatments depends on the disability level and severity of comorbidities and consists of the simultaneous provision of physiotherapy, diet and nutritional support, psychological counselling, adapted physical activity, specific nursing in hospitals with appropriate organizational and structural competences.

Weight loss and clinical characteristics of young adults patients seeking treatment at medical centers: data from the QUOVADIS Study.

OBJECTIVE: To compare clinical characteristics, attrition, weight loss, and psychological changes of obese young adults and obese adults seeking treatment. MATERIALS AND METHODS: 1530 individuals seeking treatment in 18 Italian medical centers were evaluated. 382 cases (25%) were classified as young adults (age≤35 years), 1148 (75%) as adults (>35 years). Psychological distress, binge eating, body uneasiness, and attitude towards eating were evaluated, at baseline and after a 12-month weight-loss program, together with BMI changes. Weight-loss expectations and primary motivation for seeking treatment were also recorded. RESULTS: At baseline, young adults reported significantly higher BMI at age 20, weight loss expectations and body uneasiness scores than adults. A significantly higher percentage of young adults also reported improving appearance as primary reason for seeking treatment. The attrition rate was significantly larger in young adults. Among completers, the mean percent weight loss at 12 months and improvement of psychosocial variables were significantly higher in young adults than in adults. By intention to treat, BMI changes were no longer significant between groups. DISCUSSION: Obese young adults lose more weight and considerably improve psychological distress, but show a higher attrition rate after 12 months of continuous care in a real world medical setting.

[Obesity and Eating Disorders. Indications for the different levels of care. An Italian Expert Consensus Document]. / Documento di Consensus. Obesità e Disturbi dell'Alimentazione Indicazioni per i diversi livelli di trattamento.

This paper is an Italian Expert Consensus Document on multidimensional treatment of obesity and eating disorders. The Document is based on a wide survey of expert opinion. It presents, in particular, considerations regarding how clinicians go about choosing the most appropriate site of treatment for a given patient suffering from obesity and/or eating disorders: outpatient, partial hospitalization, residential rehabilitation centre, inpatient hospitalization. In a majority of instances obesity and eating disorders are long-term diseases and require a multiprofessional team-approach. In determining an initial level of care or a change to a different level of care, it is essential to consider together the overall physical condition, medical complications, disabilities, psychiatric comorbidity, psychology, behaviour, family, social resources, environment, and available services. We first created a review manuscript, a skeleton algorithm and two rating scales, based on the published guidelines and the existing research literature. As the second point we highlighted a number of clinical questions that had to be addressed in the specific context of our National Health Service and available specialized care units. Then we submitted eleven progressive revisions of the Document to the experts up to the final synthesis that was approved by the group. Of course, from point to point, some of the individual experts would differ with the consensus view. The document can be viewed as an expert consultation and the clinical judgement must always be tailored to the particular needs of each clinical situation. We will continue to revise the Document periodically based on new research information and on reassessment of expert opinion to keep it up-to-date. The Document was not financially sponsored.

Balance in patients with anorexia and bulimia nervosa.

AIM: Neuro-muscular adaptations to the loss or increase in body weight may induce postural alterations. The aim of this study was to investigate the effect of body weight alterations on postural stability in patients with anorexia nervosa and bulimia. METHODS: The study enrolled 15 women affected by anorexia nervosa (AN), (mean body mass index [BMI] 15.8+/-1.8 kg/m(2)), 15 women affected by bulimia nervosa (BN), (mean BMI 20.1+/-2.9 kg/m(2)) and 11 healthy matched women (HC), (mean BMI 20.1+/-1 kg/m(2)). Two quiet standing conditions with eyes open (EO) and closed (EC) were analysed with an optoelectronic system (Vicon 460, Viconpeak, Oxford, UK) with passive markers to estimate the centre of mass (CoM) position. RESULTS: BN patients were more unstable than HC, showing statistically significant differences in antero-posterior CoM excursions and path length. AN patients showed non significant differences from HC. Only HC showed differences between EO and EC conditions, with significantly greater excursions in medio-lateral direction in EC condition (P<0.013) as well as an increased sway area (P<0.022). CONCLUSIONS: In BN, musculoskeletal factors seem to play a major role in the diminished postural control, which appear to be linked to body weight fluctuations rather than to BMI absolute values. No clear-cut postural instability was demonstrated in patients with AN as compared to HC. Visual input appears not to affect balance in patients with eating disorders. Possible further causes of postural instability in BN and implications for rehabilitation treatment are discussed.

Circulating ghrelin level is increased in coeliac disease as in functional dyspepsia and reverts to normal during gluten-free diet.

BACKGROUND: It is controversial whether serum ghrelin concentration is altered in coeliac disease and whether this alteration is related to nutritional impairment or to inflammatory changes of duodenal mucosa. AIM: To investigate clinical and histopathological variables affecting circulating ghrelin in coeliac patients by comparison with dyspeptic patients and with healthy controls. METHODS: We measured serum ghrelin and obtained gastric and duodenal biopsies in 44 coeliac patients before and after 1-year gluten-free diet, in 39 dyspeptic patients and 53 healthy controls. RESULTS: Serum ghrelin concentration was significantly higher in coeliac (531 +/- 29 pg/mL, P < 0.05) and in dyspeptic patients (526 +/- 14 pg/mL, P < 0.01) than in healthy controls (451 +/- 8 pg/mL), and body mass index was significantly lower in coeliac (20 +/- 1) and in dyspeptic patients (20 +/- 1) than in healthy controls (22 +/- 1, P < 0.05). In coeliac patients serum ghrelin concentration was not related to the severity of duodenal lesions. Serum ghrelin reverted to normal (399 +/- 30 pg/mL) and body mass index increased significantly (0.6 +/- 0.1 kg/m(2) increase, P < 0.05) during gluten-free diet despite persistent duodenal lymphocytic infiltration. CONCLUSIONS: Ghrelin concentration is increased and body mass index is decreased in coeliac and in dyspeptic patients irrespective of presence and severity of duodenal inflammation. Nutritional impairment is a key factor in elevating plasma ghrelin levels in coeliac disease.

Binge eating disorder in obesity: comparison of different therapeutic strategies.

The aim of this study (duration: 12 months) was to compare different integrated therapeutic approaches for the therapy of Binge Eating Disorder (BED). A sample of 65 female severely obese BED was randomly divided into 3 groups: the first one was treated by Cognitive-Behavioural Therapy (CBT) alone; the second one was treated by SSRI antidepressant therapy (fluoxetine) alone; the remaining was treated by a combination of CBT plus fluoxetine. All groups received group nutritional training and individual dietary counselling. The initial fluoxetine dose (20 mg/day) was adjusted (up to 60 mg/day) according to frequency of binge eating. During the first 4 weeks, all subjects underwent an in-patient dietary treatment aimed to achieve at least a 5% weight loss, which was continued during the out-patient treatment phase. At the beginning and at the end of the therapy the patients were evaluated by the Minnesota Multiphasic Personality - 2 and by the Eating Disorder Inventory - 2. The results showed that the two groups which underwent psychotherapy resulted in a better outcome - in terms of number of bingeing episodes, maintenance of weight loss reduction from baseline and psychological well being - than the group treated with pharmacological therapy alone. Finally, the study underlines the importance of a multidisciplinary approach to the treatment of Binge Eating Disorder.

Weight cycling and cardiovascular risk factors in obesity.

OBJECTIVE: To assess the relationship between weight cycling and some cardiovascular risk factors in a wide sample of obese subjects. DESIGN: Cross-sectional study with retrospective evaluation of weight and dieting history. SUBJECTS: In all, 459 obese subjects, 340 women and 119 men (age: 19-65 y; BMI: 30-69 kg/m2). MEASUREMENTS: Body composition and fat distribution (by bioelectrical impedance analysis and anthropometry), systolic and diastolic blood pressure, plasma glucose, total and HDL cholesterol, triglycerides, insulin and insulin resistance by HOMAir, various weight cycling indices. RESULTS: A positive correlation between weight cycling indices, BMI and percent body fat was found in both genders. Also, the maximum absolute amount of weight regained following a single diet episode was significantly associated to insulin and HOMAir in both genders. However, these correlations disappeared when the data were controlled for age and BMI. CONCLUSION: In obese subjects of both genders weight cycling, and in particular weight regain, does not appear to be associated with adverse effects on body composition, fat distribution or cardiovascular risk factors in an independent manner, but rather in relation to fat accumulation over years.

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 in advanced-stage Parkinson's disease.

Little is known about body composition in Parkinson's disease (PD). We studied 35 patients (20 male, 15 female subjects; mean age 69.7+/-5.8 years) with advanced PD by anthropometry, dual-energy X-ray absorptiometry (DEXA), and serum 25-OH vitamin D measurement. Over 70% of patients had a disease duration of more than 4 years; all were on L-dopa treatment. Low levels of serum 25-OH vitamin D were present in 41% of the patients. The mean body mass index (BMI) was 25.3+/-4.3 kg/m(2) (range 17.1-37.3). Mid-arm muscle circumference was below the 10th percentile in 23%. For whole-body mean (+/-SD) bone mineral density, the T score was below -1 SD in 35% of patients, and the Z score was below -1 SD in 24%. Percent fat mass measured with DEXA was 30.6+/-11.4% (range 10.1-45.5) in the overall sample; it was 21.1+/-8.8% (range 10.1-30.4) in male subjects and 38.1+/-9.2% (range 25.8-45.5) in female subjects. We conclude that advanced-stage PD may show excess adiposity coexisting with depletion of lean body mass (sarcopenic obesity), in addition to decreased whole-body bone mineral density associated with low serum 25-OH vitamin D. A low level of physical activity and inadequate exposure to sunlight are likely to be among the putative causes.

Effect of acute and chronic branched-chain amino acids on energy metabolism and muscle performance.

The aim of this study was to report the effects of acute and chronic branched-chain amino acids (BCAA) administration on energy metabolism and muscle performance. In the acute study which was double-blind, cross-over and placebo-controlled, 12 healthy male volunteers were administered orally on two consecutive days either BCAA (14.4 g/day) or isocaloric placebo; this was followed by measurement of oxygen consumption (VO2) and carbon dioxide production (VCO2) for 180 min by indirect calorimetry. In the chronic study, 10 healthy male volunteers were supplemented with BCAA (14.4 g/day) for 30 days. Before (T0) and after (T1) chronic BCAA administration, VO2, arm muscle area (AMA) and maximal voluntary contraction of forearm muscles (grip strength, GS) were evaluated. Acute study: Both meals increased mean respiratory quotient (RQ) from baseline: in the placebo group, this increase was short-term only (between 15 and 60 min), while this effect on RQ lasted for 120 min in the BCAA group. Moreover, between 30 and 90 min, mean RQ was significantly higher in the BCAA group than in the placebo group. Chronic study: GS increased significantly following chronic BCAA administration without significant changes in the AMA. At T0, VO2 increased significantly during the GS test, whereas at T1 no significant increase was observed. In conclusion, no excess thermogenesis could be detected as compared with placebo following acute BCAA administration, indirectly suggesting a relevant contribution of peripheral catabolic (bypassing liver) pathway to BCAA metabolism; furthermore, chronic BCAA supplementation improved the physical fitness of untrained healthy subjects, as demonstrated by the lack of 02 uptake increase during sustained hand grip test.

Immunohistochemical identification of the beta(3)-adrenoceptor in intact human adipocytes and ventricular myocardium: effect of obesity and treatment with ephedrine and caffeine.

OBJECTIVES: To investigate whether the beta(3)-adrenoceptor could be identified by immunohistochemistry in intact human white and brown adipocytes and other human tissues, and to investigate the influence of obesity and its treatment with ephedrine and caffeine on the expression of the beta(3)-adrenoceptor in adipocytes. METHODS: Morbidly obese patients were given a hypoenergetic diet (70% of energy expenditure) and some were also treated with ephedrine and caffeine (20/200 mg, three times daily) for 4 weeks. Adipose tissue and other tissues were taken during surgery. Immunohistochemistry was carried out using a monoclonal antibody raised against the human beta(3)-adrenoceptor. RESULTS: Staining was localized to the periphery of cells. All white adipocytes were stained. Those from lean subjects and obese subjects treated with ephedrine and caffeine showed more intense staining than those from untreated obese subjects. Staining was more intense in brown than in white adipocytes in perirenal adipose tissue from phaeochromocytoma patients. Staining was also seen in ventricular myocardium, and in smooth muscle of the prostate, ileum, colon and gall bladder. DISCUSSION: The tissue and subcellular distribution of staining was consistent with it being due to binding of the antibody to the human beta(3)-adrenoceptor. The presence of the beta(3)-adrenoceptor in human white adipocytes is consistent with evidence that it can mediate lipolysis in human white adipocytes. The increased expression of the beta(3)-adrenoceptor in obese subjects treated with caffeine and ephedrine supports the potential of beta(3)-adrenoceptor agonists in the treatment of obesity and type 2 diabetes. Its expression in ventricular myocardium is consistent with evidence that the beta(3)-adrenoceptor mediates a negative inotropic effect in this tissue.

Use of quality control indices in moderately hypocaloric Mediterranean diet for treatment of obesity.

A large number of studies have been published on very-low calorie diets and markedly hypocaloric dietary regimens for treatment of obesity. However, scanty data are available on moderately hypocaloric diets based on the Mediterranean diet model. We evaluated the efficacy and safety of a moderately hypocaloric Mediterranean diet (MHMD) by assessing changes in body composition and in metabolic profile in 19 obese women, aged 32+/-4 years, body weight 84.7+/-9.6 kg, body mass index (BMI) 33.67+/-2.61 kg/m2. The energy content of the diet (mean 6.5 MJ/day) matched the resting metabolic rate and its content in macronutrients (55% carbohydrate, 25% fat, 20% protein, 30 g fibre) was based on the Italian Recommended Dietary Allowances (LARN). Based on the Mediterranean diet model, available nutritional indices like the animal/vegetable protein ratio, the Cholesterol/Saturated Fat Index, the Glycaemic Index, the Atherogenic Index, the Thrombogenic Index and the Mediterranean Adequacy Index were taken into account in elaborating diets. At baseline and after 2 months, body composition by dual energy X-ray absorptiometry, metabolic profile, uric acid, fibrinogen and oral glucose tolerance test (OGTT) were assessed. Following MHMD, body weight decreased to 78.1+/-10.5 kg and BMI to 31.18+/-2.74 kg/m2. Total (-4.9+/-0.9 kg) and segmental fat mass decreased, no significant loss of total and segmental lean body mass was observed. No decrease of fasting blood glucose (5.05+/-0.45 vs 4.98+/-0.43 mmol/l, NS), of the area under the curve (AUC) for glucose (29.50+/-6.24 vs 28.07+/-5.29, NS) as well as of HDL-cholesterol (1.30+/-0.30 vs 1.33+/-0.33 mmol/l, NS) and of triglycerides (1.70+/-1.00 vs 1.46+/-0.66 mmol/l, NS) was observed. However, a significant decrease of basal insulin (11.48+/-6.77 vs 8.07+/-4.17 mU/ml, p<0.01) as well as of the AUC for insulin (263+/-118 vs 208+/-82,p<0.005), of total (5.40+/-1.04 vs 4.97+/-0.92 mmol/l,p<0.05) and LDL-cholesterol (3.36+/-1.07 vs 2.90+/-0.74 mmol/l,p<0.005), of uric acid (0.30+/-0.06 vs 0.28+/-0.05 mmol/l,p<0.01) and fibrinogen (359+/-78 vs 324+/-87 mg/100 ml, p<0.0001) was observed. In conclusion, MHMD prevents loss of fat-free mass and improves metabolic parameters in obese people. We advocate a wider use of nutritional indices and body composition assessment as tools for quality control of hypocaloric diets.

Contribution of weight cycling to serum leptin in human obesity.

OBJECTIVE: To investigate to what extent serum leptin concentrations in obese humans are influenced by a history of weight cycling. DESIGN: Cross-sectional study on serum leptin concentrations and body composition in a cohort of obese subjects in whom a retrospective recall of weight and diet history was made. SUBJECTS: One hundred and twenty-eight obese patients (89 females and 39 males), aged 18-61 y, body mass index (BMI) 31.2-63.4 kg/m(2). MEASUREMENTS: Serum leptin; various fatness and fat distribution parameters (by anthropometry and bioelectrical impedance analysis); history of overweight at puberty; number, magnitude and timing of previous diet episodes and of consequent weight regain by interview. RESULTS: By univariate analysis, serum leptin concentrations were significantly correlated with weight, waist-hip ratio, percentage body fat, maximal percentage weight loss in a single diet episode, cumulative percentage weight loss in all diet episodes, cumulative weight regained in all diet episodes, but not with the number of diet episodes. All correlations related to anthropometric and body composition parameters were stronger for men, compared to women, although the male subgroup was smaller. On the contrary, there was a strong positive correlation between weight cycling parameters and serum leptin in women but not in men. Leptin concentrations were significantly higher in patients who were overweight at puberty than in those who were not overweight at puberty. After correction for percentage body fat, presence of overweight at puberty did not correlate any longer with leptin concentrations in either gender. In women, cumulative percentage weight loss in all diet episodes contributed an additional 5% to the variance of serum leptin in the overall model. CONCLUSION: The positive correlation between weight cycling and leptin concentration in obesity is mainly accounted for the higher percentage body fat in obese weight cyclers, although in women weight cycling per se independently contributes to the variance of serum leptin.

Subclinical hypothyroidism in obese patients: relation to resting energy expenditure, serum leptin, body composition, and lipid profile.

OBJECTIVE: To evaluate whether subclinical hypothyroidism (SH) affects resting energy expenditure (REE) as well as body composition, lipid profile, and serum leptin in obese patients. RESEARCH METHODS AND PROCEDURES: A total of 108 obese patients with SH defined as normal free thyroxine levels and thyroid-stimulating hormone (TSH) values of > 4.38 microU/ml (mean +/- 2 SD of the values of our reference group of obese patients with normal thyroid function) were compared with a group of 131 obese patients matched for age, sex, and body mass index (BMI) but with normal TSH levels. We assessed estimated daily caloric intake by 7-day recall, REE by indirect calorimetry, body composition by bioelectrical impedance analysis, serum leptin by radioimmunoassay, and lipid profile (i.e., total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides). RESULTS: All of the variables measured were not different between the euthyroid obese patients and those with SH. In a multiple regression model with REE expressed for kilograms of fat free mass (REE/kgFFM) as a dependent variable and percentage of fat mass, BMI, waist-to-hip ratio, age, TSH, free thyroxine, serum leptin, and caloric intake as independent variables, only percentage of fat mass was significantly correlated with REE/kgFFM in both groups. In the SH group only, BMI, waist-to-hip ratio, age, and TSH were related to REE/kgFFM and explained 69.5% of its variability. After dividing the patients with SH using a cutoff TSH value of 5.7 microU/ml, which represents 3 SD above the mean of TSH levels of the group of obese patients with normal thyroid function, only REE/kgFFM was significantly different and lower in the group of more severely hypothyroid patients. DISCUSSION: In patients with obesity, SH affects energy expenditure only when TSH is clearly above the normal range; it does not change body composition and lipid profile. We suggest that, at least in obese patients, evaluation of TSH levels may be useful to rule out a possible impairment of resting energy expenditure due to a reduced peripheral effect of thyroid hormones.

Cholesterol metabolism in primary biliary cirrhosis during simvastatin and UDCA administration.

Little is known about the effects of cholesterol-lowering agents in hypercholesterolemic patients with primary biliary cirrhosis (PBC). The aim of this study was to compare the changes induced by simvastatin and ursodeoxycholic acid (UDCA) on cholesterol metabolism in patients with PBC and preserved liver function. Six patients with PBC were administered simvastatin (40 mg/day) for 30 days and, after a washout period of 30 days, ursodeoxycholic acid (600 mg/day) for 30 days. Serum levels of lathosterol, campesterol, 7 alpha-hydroxycholesterol, and 27-hydroxycholesterol were measured by gas chromatography-mass spectrometry. During simvastatin administration, reduction of cholesterol levels (34% in 30 days) was paralleled by the decrease of lathosterol (55%), whereas concentrations of campesterol and of the two hydroxysterols were not substantially modified. During ursodeoxycholic acid administration, a trend toward a decrease of serum cholesterol concentrations was observed after only one year of treatment, and these changes were paralleled by the decrease of campesterol serum levels. Both simvastatin and UDCA were well tolerated, and a reduction of serum liver enzyme levels occurred with the latter. Simvastatin proved to be safe and effective in reducing serum cholesterol levels in patients with PBC by an inhibitory effect on cholesterol synthesis occurring within 24 h. --Del Puppo, M., M. Galli Kienle, A. Crosignani, M. L. Petroni, B. Amati, M. Zuin, and M. Podda. Cholesterol metabolism in primary biliary cirrhosis during simvastatin and UDCA administration. J. Lipid Res. 2001. 42: 437--441.

Ursodeoxycholic acid alone or with chenodeoxycholic acid for dissolution of cholesterol gallstones: a randomized multicentre trial. The British-Italian Gallstone Study group.

BACKGROUND: Combination therapy using ursodeoxycholic acid plus chenodeoxycholic acid has been advocated for dissolution of cholesterol gallstones because the two bile acids have complementary effects on biliary lipid metabolism and cholesterol solubilization. AIM: To compare the clinical efficacy of combination therapy with ursodeoxycholic acid monotherapy. PATIENTS AND METHODS: A total of 154 symptomatic patients with radiolucent stones (< or = 15 mm) in functioning gallbladders were enrolled from six centres in England and Italy. They were randomized to either a combination of chenodeoxycholic acid plus ursodeoxycholic acid (5 mg.day/kg each) or to ursodeoxycholic acid alone (10 mg.day/kg). Dissolution was assessed by 6-monthly oral cholecystography and ultrasonography for up to 24 months. RESULTS: Both regimens reduced the frequency of biliary pain and there was no significant difference between them in terms of side-effects or dropout rate. Complete gallstone dissolution on an intention-to-treat basis was similar at all time intervals. At 24 months this was 28% with ursodeoxycholic acid alone and 30% with combination therapy. The mean dissolution rates at 6 and 12 months were 47% and 59% with ursodeoxycholic acid, and 44% and 59% with combination therapy, respectively. CONCLUSION: There is no substantial difference in the efficacy of combined ursodeoxycholic acid and chenodeoxycholic acid and that of ursodeoxycholic acid alone in terms of gallstone dissolution rate, complete gallstone dissolution, or relief of biliary pain.

Leptin plasma concentrations are dependent on body fat distribution in obese patients.

AIM: To evaluate whether fat distribution plays a role in determining serum leptin concentrations. PATIENTS AND METHODS: One-hundred and forty-seven obese patients, 77 males and 70 females, aged 45.1 +/- 13.2 y (mean +/- s.d.; range 21-73 y), with body mass index (BMI) ranging from 30 to 55 kg/m2 (mean 42.3 +/- 5.9). Ultrasound assessment of the thickness of subcutaneous and preperitoneal fat was carried out and calculation of their ratio as abdominal fat index (AFI), waist-hip ratio (WHR), body composition by bioelectrical impedance to evaluate the percentage of fat mass (FM%) and total amount of fat (FMKg) were also determined. Plasma leptin was measured by radio immuno assay (RIA). RESULTS: In the whole group of patients, serum leptin concentrations were 37.2 +/- 18.4 ng/ml (range 6-101.3 ng/ml); in spite of BMI values not being significantly different, women had leptin values significantly higher (47.4 +/- 17.4 ng/ml) (P < 0.01) than males (28.1 +/- 15.1 ng/ml), also after correction for fat mass. The mean thickness of abdominal subcutaneous fat was 33.7 +/- 12.9 mm and it was significantly (P < 0.001) higher in female (40.9 +/- 10.6 mm) than in male (27.1 +/- 11.2 mm) patients; preperitoneal thickness was 22.9 +/- 7.1 mm, with significantly (P < 0.05) higher values in males (24.2 +/- 6.8 mm) than in females (21.7 +/- 7.3 mm). Accordingly, AFI (in all patients 0.84 +/- 0.6) was significantly higher in males (1.09 +/- 0.6) than in females (0.56 +/- 0.2). In the overall population, leptin concentrations were directly and significantly related to subcutaneous but not preperitoneal fat; they showed a strong inverse relationship with AFI and WHR. When the results were evaluated dividing the patients according to gender, subcutaneous fat thickness showed a stronger association with leptin levels in males than in females, whereas no association was found with preperitoneal fat thickness. Leptin and AFI values were significantly related only in men. WHR values were not correlated with leptin concentrations in either sex. When fat mass was added to the model, subcutaneous fat thickness, AFI and WHR remained independently associated with leptin concentrations. Age and diabetes did not influence these measures. CONCLUSIONS: Fat distribution contributes to the variability in serum leptin in obese patients. In particular, subcutaneous abdominal fat is a determinant of leptin concentration, also independently of the amount of fat mass, whereas the contribution of preperitoneal visceral fat is not significant.

Glucocorticoids and neuroendocrine function.

Recent experimental evidence supports the role of glucocorticoids in the neuroendocrine control of food intake and energy expenditure. In particular, glucocorticoids promote food consumption directly through stimulation of NPY and inhibition of CRH and melanocortin release. CRH and NPY are also functionally linked by a mutual regulation. CRH is anorexigenic when secreted acutely while it exerts the opposite effect when, upon sustained secretion, it stimulates the hypothalamo-pituitary-adrenal (HPA) axis. The orexigenic effects of glucocorticoids are counteracted by a steroid-induced rise in leptin levels that closes a regulatory loop regarding food consumption. Furthermore, glucocorticoids may alter body fat distribution, increasing truncal adiposity both directly and by inhibition of growth hormone secretion. No clearcut alterations of the HPA function are apparent in obesity as a whole. However, subtle and specific abnormalities may be noted in subsets of obese patients. Indeed, obesity, mostly visceral type, is associated with an increased cortisol clearance and 11-beta hydroxysteroid dehydrogenase activity in the omental fat. In the same vein, an increased cortisol rise following a mixed meal has been observed in obese subjects. Finally, it has been proposed that adrenal incidentalomas, often characterized by enhanced cortisol secretion, might be a clinical expression of the X syndrome.