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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.

Relationships between obesity and fat distribution as evaluated by computed tomography and metabolic variables were studied in 35 men. Significant correlations emerged between body mass index and sum of glucose during oral glucose load and HDL3 triglycerides and also between visceral abdominal fat and triglycerides, apolipoprotein B, sum of insulin during oral glucose load, very-low-density-lipoprotein (VLDL) cholesterol, and VLDL and low-density-lipoprotein (LDL) triglycerides. Visceral abdominal fat correlated negatively with the ratio of HDL to LDL cholesterol. When the subjects were subdivided into four groups according to body mass index (or = 26.7,26.7) and median visceral abdominal fat, no significant differences were found in body mass index, whereas significant differences were found for triglycerides, cholesterol, apolipoprotein B, VLDL cholesterol, HDL:LDL cholesterol, and VLDL triglycerides. Our study shows that the amount of visceral abdominal fat is the most relevant factor for metabolic abnormalities. Our data also suggest that the effect of visceral fat is independent of body mass index.

Alzheimer s disease is the most frequent cause of dementia in elderly people and it is one of the leading causes of death among older individuals. Weight loss is a frequent clinical finding in Alzheimer s disease patients, and it is actually listed as a symptom consistent with the diagnosis of Alzheimer s disease, but its significance has not been clearly understood until now. This review examines the role of the components of energy balance in determining weight loss in AD patients, on the basis of data collected from the literature. We also considered the possible causes of anorexia in AD patients. In the last years many researchers investigated the possible role of abnormally high energy expenditure, or low energy intakes, or both, to explain weight loss in these patients. Studies on energy intake, energy expenditure and body composition in AD patients have been reviewed. The results of published studies do not seem to support the hypothesis of an hypermetabolic state or inadequate energy intake in AD patients, but further studies, with greater samples are necessary in the future to investigate weight loss in AD patients. A better understanding of this finding could be important to obtain the maximal lifespan of demented patients.

There is increasing evidence for the existence of a condition consisting of a cluster of metabolic disorders which include insulin resistance, alterations in glucose and lipid metabolism, increased blood pressure and visceral obesity. The metabolic syndrome is now the favoured definition of the cluster. Each single component of the cluster increases the cardiovascular risk, but the combination of factors is much more important. Insulin resistance is the most frequently associated factor to the singular components of the syndrome: most authors believe that it may be the common aetiological factor. However, visceral obesity seems to be the main driving factor by means of the increased production of free fatty acids whose activity, in turn, might interfere with the action of insulin. Some questions exist about the syndrome because of the frequent lack in the cluster of one of the factors. This does not mean that the missing factor does not belong to the syndrome, but only that it is not yet clinically evident. Weight gain has been shown to be a strong predictor of the metabolic syndrome. This aspect gives strength to treatment and prevention because it means that losing weight or stopping weight increase might reduce the risk of a future appearance of a factor that is still not evident. Interventions to treat visceral obesity by means of losing weight seem to be the most efficacious way to treat the metabolic syndrome thus improving the most widespread cardiovascular risk factor in western countries.

Elevated homocysteine increases the risk of vascular diseases but little information is available about this issue in the elderly. The aim of this cross-sectional study was to evaluate the relationships between homocysteinemia and gender, anthropometric, and life-style characteristics in a community-dwelling elderly population (65 men and 120 women; 67-78 years). Basal plasma homocysteine levels were determined by High Performance Liquid Chromatography (HPLC). Clinical records, and nutritional and anthropometric variables were collected in all subjects. Body composition was evaluated in all subjects by Dual energy X-ray Absorptiometry (DXA). Thirty-three percent of women and 66% of men had hyper-homocysteinemia. In women, a positive correlation was present between homocysteinemia, age, diastolic blood pressure and plasmatic creatinine, and a negative correlation between homocysteine, fiber intake and folates. In males, there was a positive correlation between plasma homocysteine, age, and body mass index. Multiple regression analysis showed that fat-free mass, cigarette smoking, fiber intake, vitamin B6 and total kcal intake accounted for 18% of homocysteine variance in males (R2 = 0.18, p0.05). Significantly higher homocysteine values were found in women with a history of cardiovascular disease than in those without (16.6 +/- 9.4 vs 13.8 +/- 4.4 micromol/L, p0.05). Homocysteinemia was significantly higher in elderly men compared to women (16.7 +/- 4.7 vs 15.3 +/- 7.6; p0.05). Gender differences in homocysteine disappeared after adjusting for fat-free mass. This study confirms the age-related increase in plasma homocysteine. Life-style characteristics seem to influence significantly homocysteine levels in the elderly. Our study shows that gender effects on homocysteine may be attributed to differences in body composition.

High lipoprotein(a) [Lp(a)] has been observed in patients with ischemic heart disease and cerebrovascular disease. Lp(a) is actually thought to be an independent risk factor for coronary disease. We therefore carried out a case-control study, evaluating plasma Lp(a) in 61 patients with angiographically documented peripheral arterial disease (PAD) and in 61 age- and sex-matched patients with no cardiovascular disease. General risk factors for vascular disease were also taken into account. Lp(a) was significantly higher in patients than controls (257.0 +/- 34.8 vs 146.5 +/- 23.5 mg/l p0.05), as were cigarette smoking, diabetes, cholesterolemia, fibrinogenemia and the waist-to-hip circumference ratio. Stepwise logistic regression analysis showed that, in addition to cigarette smoking, diabetes, cholesterol and fibrinogen, Lp(a) is a significant independent risk indicator for PAD. This result suggests that high plasma Lp(a) is associated with enhanced risk of PAD and must therefore be evaluated alongside traditional risk factors.

The effect of almonds as part of a low saturated fat, low cholesterol, high-fiber diet was studied in 26 adults (13 men, 13 women). The baseline diet was modified in a similar way for all subjects by limiting meat, fatty fish, high-fat milk products, eggs, and saturated fat. Grains, beans, vegetables, fruit, and low-fat milk products were the foundation of the diet. During the almond diet period, raw almonds (100 mg/day) supplied 34 g/day of monounsaturated fatty acid (MUFA), 12 g/day of polyunsaturated fatty acid, and 6 g/day of saturated fatty acid. Almond oil was the only oil allowed for food preparation. There was a rapid and sustained reduction in low-density lipoprotein cholesterol without changes in high-density lipoprotein cholesterol. This was reflected in a total plasma cholesterol decrease from (means +/- SEM) 235 +/- 5.0 at baseline to 215 +/- 5.0 at 3 weeks, and to 214 +/- 5.0 mg/dl at 9 weeks (p less than 0.001). When the consumption of nuts high in MUFA increases the fat content of the diet, reduction rather than elevation of plasma cholesterol has to be expected, possibly due to the MUFA content of these nuts.

On 5 and 6 April 1991, at the National Research Council (CNR) in Rome, a Consensus Conference on the relationship between overweight, obesity and health was held. The conference was sponsored by FATMA (Applied Project on Disease Factors of the CNR) and UICO (Italian Society for the Study of Obesity) with the purpose of establishing guidelines for health employees. The development of the conference followed the methodology set down by OMAR to obtain a rational and significant consensus on the answers to six basic questions prepared by the planning committee. The questions were the pivotal point of the conference and were brought to the attention of all the attendees and widely diffused among the medical community; they were proposed with the aim of giving an exhaustive definition of obesity, to investigate its relationship with mortality and morbidity, to highlight its social characterization, to indicate methods of evaluation and recommendations for weight loss, to select groups at risk, and to focus general guidelines for research. After the presentation of the state of the art on 18 topics by experts in the field, the 22 members of the consensus panel, impartial experts from a vast area of the scientific community, discussed a draft document representing the answers to the questions, which was subsequently submitted to the 307 attendees, discussed and then approved. This paper is the definitive document of the Consensus Conference. The introduction explains the reasons which led to the decision to promote the conference six years after the one held in the United States. The methodology is then set out. The questions are answered in the form of recommendations and backed up by data and scientific evidence from the literature.

Incorporation of 3.3 g sodium propionate per 50 g available carbohydrate portion of bread reduced acutely the blood glucose response area in six healthy volunteers by 47.6 +/- 12.1% Similarly, in vitro digestibility was reduced by 47.4 +/- 1.1% (P less than 0.01). One week of dietary supplementation with 9.9 g sodium propionate in bread/d reduced the blood glucose area in comparison with standard propionate-free bread by 38.0 +/- 8.7% (P less than 0.05), but increased fecal bulk by 28.3 +/- 8.7% (P less than 0.05) and anaerobic microflora by 0.564 +/- 0.165 X 10(6)/g feces (P less than 0.05), specifically as bifidobacteria. Day-long breath hydrogen concentrations did not increase after 1 wk on propionate bread but methane production increased in the three methane producers. Although lipid changes were not significant, five subjects showed reduced high-density-lipoprotein and increased triglyceride concentrations, both of which correlated with increased fecal weight (P less than 0.05). Because propionate reduces the rate of starch digestion, studies using oral propionate must take into account its action as an enzyme inhibitor.

On April 5th and 6th 1991, at the National Research Council (CNR) in Rome, a Consensus Conference on the relationship between Overweight, Obesity and Health was held. The Conference was sponsored by FATMA (Applied Project on Disease Factors of the CNR) and UICO (Italian Society for the Study of Obesity) with the purpose of establishing guidelines for health employees. The development of the Conference followed the methodology set down by OMAR to obtain a rational and significant consensus on the answers to 6 basic questions prepared by the Planning Committee. The questions were the pivotal point of the Conference and were brought to the attention of all the attendees and widely diffused among the medical community; they were proposed with the aim of giving an exhaustive definition of obesity, to investigate its relationship with mortality and morbidity, to highlight its social characterization, to indicate methods of evaluation and recommendations for weight loss, to select groups at risk, and to focus general guidelines for research. After the presentation of the state of the art on 18 topics by experts in the field, the 22 members of the Consensus Panel, impartial experts from a vast area of the scientific community, discussed a draft document representing the answers to the questions, which was subsequently illustrated to the 307 attendees, discussed and then approved. This paper is the definitive document of the Consensus Conference. The introduction explains the reasons which led to the decision to promote the Conference six years after the one held in the United States. The methodology is then set out. The questions are answered in the form of recommendations and backed up by data and scientific demonstrations from the literature.

Various methods to assess lean and fat body masses and abdominal-visceral adipose tissue were compared in 26 obese women on extremely hypocaloric diets. The following anthropometric parameters were measured before and after 15 days of extreme calorie restriction: arm circumference (A), waist circumference (W), hip circumference (H) and thigh circumference (T); W/H, W/T, A/H and A/T ratios; subcutaneous biceps , triceps , subscapular, abdominal and thigh folds; echographic thickness of abdominal muscle-aorta; area of visceral (VAT), total (AT) and subcutaneous adipose tissue measured using computed tomography, lean and fat body masses assessed by impedance measurement. Under standard conditions it was shown that echography, like impedance measurement, was the most useful method for assessing lean and fat body masses in obese subjects, whereas plicometry was not found reliable. On extremely hypocaloric diets, echography is able to assess the variations of lean and fat body masses, whereas impedance measurement overestimated the lean body mass. Localisation indexes of visceral fat based on body circumferences were shown not to be suitable for the evaluation of changes in visceral adipose tissue, at least when these were slight. Echography was also the most useful method to assess slight changes in visceral adipose tissue.

It has been demonstrated that cells with poor or no lipid content, isolated from epididymal fat pads of young rats, develop fully into mature adipocytes in vitro. The ultrastructural feature of these cells during such a development have been studied recently. In the present work the electron microscopic aspects of similarly obtained cells from adult rats have been investigated. It has been found that no morphological differences are present in the cells immediately after isolation between young and adult rats. During culture the cells from both adult and young rats show the same maturative process, but in adult rats this process is generally slower and not homogeneous, suggesting the presence of two populations of adipocyte precursors. The former accumulate lipids quickly and have electron microscopic features very similar to those observed for young rat precursors, however maturation is still faster in the latter cells. The latter have electron microscopic aspects of less differentiated cells (some fibroblast-like features) during the first days of culture; however they show a similar development when longer culture periods are studied. These data suggest that the fibroblast-like cells seen after a period of time in culture probably represent an early stage of adipocyte precursor differentiation. Thus it is suggested that in adult mammals, there may be a population of adipocyte precursors present within the adipose tissue which upon stimulation by as yet unknown factors would develop fully into adipocytes.

To study the mechanism(s) of action of metformin, fragments of human subcutaneous adipose tissue were incubated with therapeutic blood concentrations of metformin. In the absence of insulin no effect of metformin was seen on either lipolysis or glucose metabolism. When insulin was present, however, metformin stimulated glucose conversion into both triglycerides and CO2. In marked contrast, no effect of metformin was observed on the antilipolytic effect of insulin. In agreement with this selective effect no change in insulin binding was found. In conclusion, metformin seems to exert its effect on glucose metabolism by potentiating the action of insulin at a post-receptor level, possibly on the rate of glucose transport.

Twelve patients with body weight varying from 106 to 163 Kg, underwent jejunoileal bypass operations; their oral glucose tolerance tests (oGTT) were evaluated before the operation and one, five, and fifteen months afterwards. The lowering of the glycemic curve and the decrease of the insulinemia values during oGTT have been studied in relation to intestinal absorption deficit and weight loss. It is concluded that weight loss was the main factor determining the improvement of glucose metabolism.

Results obtained in an investigation of two groups of obese and grossly obese subjects are presented. Poorer carbohydrate tolerance was noted in the latter. Blood insulin patterns after oral glucose loading, however, were less easy to interpret. Overall, the values were much the same in the two groups. Nevertheless, analysis of the curves showed that the grossly obese displayed a later peak.

Interscapular brown adipose tissue was removed from young rats, the cells isolated using collagenase, pelleted by centrifugation and cultured. Ultrastructural observations were made on these cells immediately after isolation and on Days 1, 2, 4, 10 and 14 of culture. The isolated cells show the typical submicroscopic features of cells in intact brown adipose tissue, i.e. a multivacuolar lipid depot and numerous typical mitochondria with dense cristae. However, as early as Day 1 of culture, the cells show degeneration of the typical mitochondria which are probably then extruded from the cells. Atypical mitochondria now begin to appear and become dominant on Day 4 of culture. By contrast, the typical multivacuolar shape of the lipid droplet does not change. Not even after prolonged periods of culture (2-4 weeks) is there any evidence of coalescence of the multivacuolar lipid depot. These findings are consistent with the possibility that the typical mitochondria of brown adipocytes depend on in vivo conditions, perhaps adrenergic innervation, while the multivacuolar characteristic of the lipid depot does not, and may be an intrinsic feature of the brown adipose cell.

The activity of lipoprotein-lipase in heparin-eluates of adipose tissue (AT-LPLA) of three body regions was measured in 22 obese and 18 nonobese females under basal conditions. AT-LPLA in the obese women both before and after 10 d of caloric restriction was also measured. Basal LPLA correlated well with plasma insulin values and reduced significantly after caloric restriction. Relative body weight, body fat, fasting and glucose-stimulated insulin levels, triglycerides, total cholesterol, but not high-density lipoprotein cholesterol, significantly decreased after caloric restriction. Variation of insulin levels after caloric restriction was the best explanatory variable correlating with AT-LPLA variations. These results are consistent with a primary role of insulin in regulating AT-LPLA.

Insulin binding to human adipose tissue from surgical patients was determined after three different preincubation conditions: a) 24 hrs in the presence or absence of 80 ng/ml insulin; b) 24 hrs in the presence of 80 ng/ml insulin or insulin plus 4 micrograms/ml metformin; c) 48 hrs pre-incubation as in b). We found that insulin down regulated its own receptor after 24 hours pre-incubation; when metformin was present in the pre-incubation medium together with insulin, insulin binding to adipose tissue was significantly higher than in tissue exposed to insulin alone after 48 hrs pre-incubation; a similar effect of metformin was already seen after 24 hrs, but was not statistically significant. We suggest that metformin can correct down regulation of the insulin receptor. This finding could explain discrepant results among studies dealing with the influence of metformin on insulin binding. Moreover, these results could be useful in understanding the mechanism of action of metformin in insulin-resistant states, e.g. type II diabetes.

Sugar and fat metabolism were studied in a group of obese women without diabetes. Blood triglicerides and cholesterol were, on average, within normal limits, though endogenous hypertriglyceridaemia was noted in a few cases. Triglycerides were significantly related to blood sugar (baseline and after glucose loading), whereas there was no significant connection with blood insulin. The meaning of these results is discussed.

In order to attempt to characterize the adipocyte precursor cell in situ in developing adipose tissues from young rats, the light and electron microscopic characteristics were determined of cells in situ in these tissues, as well as in suspensions from the same tissues of cells liberated with collagenase subsequently developing to adipocytes in culture. The functional characteristics of adipose precursor cells at different stages of development in culture is known from previous work, and could therefore be added in parallel to the morphological characteristics. In order to allow comparison with fibroblasts from a site where adipocyte formation does not occur, lung-fibroblasts were also studied in parallel cultures. In culture, a rapidly dividing cell confluenced and reached full expression to adipocytes. This cell had morphological characteristics developing at the same time as early lipid accumulation making it easily distinguishable from a lung fibroblast in culture. A similar cell was found in abundance in the peripheral, non-developed part of the intact epididymal fat pad, here often surrounded by collagen. However, the early preadipocyte (without lipid droplets) and the adipoblast cannot be morphologically distinguished in situ from the fibroblast; therefore it cannot be excluded that fibroblasts and adipoblasts are the same cells in adipose tissue, possibly deriving from the pericyte.

Hyperinsulinism may play a role in the development of atherosclerosis. In this study we analyzed the interrelationships between plasma glucose, insulin, body weight and high-density lipoproteins (HDL) in a group of obese women and faced the question of what is the effect of obesity on insulin, glucose and HDL relationships. HDL cholesterol was significantly lower, while HDL triglycerides resulted significantly higher in the obese women than in the controls. The two groups did not show any difference in the serum concentration of HDL apoprotein A-I and apoprotein A-II. There was an inverse correlation between fasting plasma glucose and summated means of glucose and insulin levels after an oral glucose tolerance test and HDL cholesterol in the two groups; on the contrary a positive relationship between the same parameters and HDL triglyceride occurred. HDL cholesterol was inversely related also to the weight index, while HDL triglyceride concentration was directly correlated with this parameter in the two groups. Partial correlation analysis demonstrates that, when exposed to similar plasma insulin and glucose levels, HDL cholesterol and triglyceride concentrations were no longer correlated with the weight index, and therefore that the significant correlations between these variables are likely to be due to the significant correlations of each of them with plasma glucose and insulin levels. Further studies clarifying the role of glucose and insulin in determining HDL composition would appear important.

One hundred thirty subjects were studied to investigate relationships between the body composition and fat distribution as evaluated by computed tomography and the resting metabolic rate (RMR) as evaluated by indirect calorimetry: 82 premenopausal women (age, 18 to 52 years; body mass index [BMI], 27 to 52 kg/m 2 ), 27 postmenopausal women (46 to 71 years; 28 to 49 kg/m 2 ), and 21 men (18 to 70 years; 31 to 43 kg/m 2 ). The thermic effect of food (TEF) was evaluated in all men and in 2 subgroups of 55 and 19 women. The best-fitting equations for predicting RMR, obtained by multiple regression, included the following as covariates: fat-free mass and both subcutaneous and visceral adipose tissue in premenopausal women ( R 2 = .55, P = .0001), fat-free mass and visceral adipose tissue in postmenopausal women ( R 2 = .58, P = .001), and age, with minus sign, and visceral adipose tissue in men ( R 2 = .44, P = .0051). Fasting insulin and fat-free mass, with minus sign, and both visceral and subcutaneous adipose tissue were the predictors of the TEF ( R 2 = .25, P = .0055) in premenopausal women. This study demonstrates that visceral fat distribution is important in determining the RMR in postmenopausal women and men. In premenopausal women, total adipose tissue is a main determinant of both the RMR and TEF. This last effect could be counterbalanced by insulin resistance.

La terapia dell'obesità è un dilemma: a volte i risultati sono troppo facili, anche in assenza di qualsiasi razionale o professionalità. Qualsiasi individuo può perdere peso da solo e chiunque può mettersi a fare la professione, anche senza alcuna competenza. A volte, ed è quasi la regola, la situazione è talmente problematica che i pazienti obesi (e i loro medici) annoverano una tale successione di fallimenti da abbassare il livello dell'autoefficacia e quindi dell'autostima ("self-efficacy": processo cognitivo della percezione della propria competenza e abilità nel compiere una determinata azione). Si deve pertanto attivare un rapporto relazionale terapeutico a triangolo paziente-medico-malattia e ogni lato deve trovare la sua giusta dimensione e interazione. Risultati troppo facili generano eccessivi entusiasmi che non permettono alcuna riproduicibilità; il successo è destinato al fallimento per la ripresa del peso perduto. Le fortune commerciali della "diet industry" non hanno limite: in America si calcola che vengano spesi, ogni anno, 30 bilioni di dollari per il controllo del peso. Se i risultati sonmo problematici i pazienti sono obbligati a ricercare terapie aggressive, cruente e prescrittive e spesso si abbandonano alle frodi ed alle mistificazioni. Il risultato non è mai quello desiderato: ottenere, cioè, una migliore qualità della vita ed una migliore aspettativa per la riduzione del rischio di mortalità. La lezione della storia non è ancora definita. Pochi l'hanno imparata e poco viene insegnata dall'Accademia.

La NAFLD è una malattia epatica di sempre più frequente rilievo in individui di tutte le età e di ogni razza, senza distinzione di sesso; rappresenta oggi la principale causa di malattia cronica epatica in molti Paesi. È generalmente associata ad obesità, diabete e dislipidemia, ma può presentarsi anche in soggetti magri e con normale tolleranza glucidica. Nella maggior parte dei casi è associata ad insulino-resistenza, che favorisce il deposito di lipidi anche al di fuori del tessuto adiposo. Alla sua patogenesi concorrono numerosi fattori: una possibile base genetica, stili di vita a rischio, lo stress ossidativo, la produzione di citochine. L’assenza di una franca sintomatologia porta alla diagnosi in modo occasionale per transaminasi alterate o fegato brillante all’ecografia, ma la conferma e la stadiazione della malattia si basano esclusivamente sulla biopsia epatica.