Rita Manini

A randomized controlled trial of metformin versus vitamin E or prescriptive diet in nonalcoholic fatty liver disease.

OBJECTIVES:Metformin proved useful in the treatment of nonalcoholic fatty liver disease (NAFLD), but its superiority over nutritional treatment and antioxidants has never been demonstrated. We aimed to compare the usefulness of metformin versus prescriptive diet or vitamin E.METHODS:In an open label, randomized trial, nondiabetic NAFLD patients were given metformin (2 g/day; n = 55) for 12 months. The control cases were given either vitamin E (800 IU/day; n = 28) or were treated by a prescriptive, weight-reducing diet (n = 27). Outcome measures were liver enzymes, insulin resistance (homeostasis model assessment), parameters of the metabolic syndrome, and histology.RESULTS:Aminotransferase levels improved in all groups, in association with weight loss. The effects in the metformin arm were larger (p < 0.0001), and alanine aminotransferase normalized in 56% of cases (odds ratio (OR) versus. controls, 3.11; 95% confidence interval (CI), 1.56–6.20; p = 0.0013). In multivariate analysis, metformin treatment was associated with higher rates of aminotransferase normalization, after correction for age, gender, basal aminotransferases, and change in body mass index (OR, 5.98; 95% CI, 2.05–17.45). Differences were maintained when the two control groups were separately analyzed. The distribution of positive criteria for the metabolic syndrome was reduced only in the metformin arm (p = 0.001, signed rank test). A control biopsy in 17 metformin-treated cases (14 nonresponders) showed a significant decrease in liver fat (p = 0.0004), necroinflammation, and fibrosis (p = 0.012 for both). No side effects were observed during metformin treatment.CONCLUSIONS:Metformin treatment is better than a prescriptive diet or vitamin E in the therapy of NAFLD patients receiving nutritional counseling. Limited histological data support an association between improved aminotransferases and biopsy findings, which require confirmation in a double-blind trial with appropriate statistical power based on liver histology.

WHO and ATPIII proposals for the definition of the metabolic syndrome in patients with Type 2 diabetes

Aims  Different criteria have been proposed by the World Health Organization (WHO) and by the Third Report of the National Cholesterol Education Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATPIII) for the diagnosis of the metabolic syndrome. Its identification is of particular importance for coronary risk assessment.

Effects of cognitive–behavioural therapy on health-related quality of life in obese subjects with and without binge eating disorder

OBJECTIVE: To measure the effects of cognitive–behavioural therapy on health-related quality of life (HRQL) in obese patients, in relation to binge eating disorder.DESIGN: Longitudinal, clinical intervention study consisting of structured sessions of cognitive–behavioural therapy, preceded by sessions chaired by a psychologist in subjects with binge eating.SUBJECTS: Two groups of obese patients (92 treated by cognitive–behavioural therapy (77 females); 76 untreated controls (67 female), selected from the waiting list (control group)). Of 92 treated patients, 46 had a binge eating disorder at psychometric testing and structured clinical interview.MEASUREMENTS: Health-related quality of life by means of Short-Form 36 questionnaire at baseline and after 3–5 months.RESULTS: Cognitive–behavioural treatment produced an average weight loss of 9.4±7.5 kg, corresponding to a BMI reduction of 3.48±2.70 kg/m2. No changes were observed in the control group. All scales of HRQL improved in treated subjects (by 5–19%). In obese subjects with binge eating weight loss was lower in comparison to non-bingers (7.7±8.1 vs 11.1±6.6; P=0.034). However, the improvement in HRQL was on average larger, and significantly so for Role Limitation—Physical (P=0.006), Role Limitation—Emotional (P=0.002), Vitality (P=0.003), Mental Health (P=0.032) and Social Functioning (P=0.034). Bodily Pain was the sole scale whose changes paralleled changes in body weight.CONCLUSIONS: The positive effects of cognitive–behavioural therapy, mainly in subjects with binge eating, largely outweigh the effects on body weight, resulting in a significant change in self-perceived health status.

A physical activity program to reinforce weight maintenance following a behavior program in overweight/obese subjects

Objective:To investigate the effects of a specific program to implement physical activity (fitness program) on weight loss maintenance, activity level and resting energy expenditure (REE).Design:Observational study of subjects completing a behavioral program.Subjects:In total, 200 overweight/obese subjects (36 males, aged 20–66 years; average BMI, 35.2 kg/m2).Program and measurements:The fitness program consisted of 12 bimonthly sessions, chaired by doctors and dietitians, involving groups of 8–12 subjects. Patients entered the program approximately 9 months after the end of behavioral treatment, during a weight loss maintenance period. The goal was set at a light-to-moderate daily physical activity (brisk walking), quantitatively measured by a pedometer; REE was measured before and after the fitness program by indirect calorimetry in a subset of patients.Results:The fitness program restarted the process of weight loss in over 60% of subjects. At the end of the study, 84% of patients walked at least 5000 steps per day, compared with 24% at the beginning of the study. The probability of losing from 5 to 10% of initial body weight increased by 20% for any 1000 steps/day (OR, 1.20; 95% CI (confidence interval), 1.07–1.35), and that of losing more than 10% by over 30% (OR, 1.33; 95% CI, 1.19–1.49). REE increased significantly by 100 kcal/day (+7.5%), in spite of further weight loss (−1.8%).Conclusion:A specific fitness program in the weight maintenance phase after a behavioral program may significantly improve the long-term control of obesity.

Cognitive behavioural therapy for obesity: One-year follow-up in a clinical setting

Cognitive behavioural therapy (CBT) is the most comprehensive means of medically treating obesity, but only few data have so far been published concerning its long-term effectiveness. We here report our experience of 1068 consecutive patients (868 females) treated with CBT at a university-based obesity centre. The patients were enrolled into three different programmes: a 14-week LEARN programme (672 patients), a 16-week MOB programme for the morbidly obese (259 patients), or a 20-week BINGE programme for subjects affected by binge eating (137 patients). Eighty-five percent of the subjects completed the weekly programmes. The percentage of patients attending the scheduled control visits during the 1-year follow-up gradually decreased, being very low in the BINGE group (10%). The percentage weight loss was an average of 6% during the weekly courses, being higher in the MOB programme; by the end of the weekly sessions, it exceeded 10% of initial body weight in 22% of cases and increased to 36% during the follow-up. The cumulative probability of follow-up was higher among the patients undergoing the MOB and LEARN programmes than among the BINGE patients (p<0.0001), and decreased with the increasing severity of obesity. Female gender and a weight loss of >10% i.b.w. increased compliance to follow-up. The study further demonstrates the difficulty of achieving compliance to chronic management of obesity and the critical role of binge eating disorder in the medium-term treatment of obesity. Strategies are needed to improve adherence to a follow-up protocol.

Review article: the treatment of fatty liver disease associated with the metabolic syndrome

The treatment of non‐alcoholic fatty liver disease may be worthwhile to prevent progression to advanced liver failure, but no therapy is definitely evidence‐based. Weight loss or lifestyle modifications remain the primary line of intervention, particularly in overweight or obese subjects. In adult non‐alcoholic fatty liver disease, they are effective in the short‐term, but require a multidisciplinary team approach that is rarely available in liver units. Insulin‐sensitizing agents are probably the treatment of choice. They definitely reduce the insulin resistance that promotes steatosis. Several uncontrolled and controlled studies have documented an improvement in liver biochemistry and in histology, but the long‐term results remain unsettled. This is an area where significant advances are expected in the next few years.

Homocysteine and psychological traits: a study in obesity

OBJECTIVE Total serum homocysteine is a risk factor for cardiovascular disease in the general population. Further, homocysteine might be the link between psychological traits (namely anger and hostility) and cardiovascular disease, mediated by stressful events and sympathetic nervous tone. METHODS We measured total plasma homocysteine levels and psychological traits in 205 obese individuals entering a weight-reduction program (162 females; age range, 17-64 years; body mass index, 37.7 +/- 6.2 kg/m(2), mean +/- standard deviation). Psychometric assessment was performed with three self-administered questionnaires (Symptom Checklist 90, composed of nine subscales including Hostility/Anger and Depression scales; Beck Depression Inventory; and Binge Eating Scale). RESULTS Homocysteine levels were moderately increased in obese individuals when compared with the normal population and higher in males (median, 12.9 micromol/L; range, 6.9-26.3) than in females (9.8; 4.6-24.6; P < 0.0002), but not different in relation to the severity of obesity. Serum folate and vitamin B12 were normal. Psychometric testing showed pathologic data in up to 50% of patients and the Anger/Hostility scale was positive in 24%, mainly female, subjects. There were no differences in psychological traits in relation to the severity of obesity. Homocysteine did not correlate with Symptom Checklist 90 values or other values of psychometric testing. CONCLUSIONS In obese persons, psychological traits are not major determinants of total homocysteine. A different response to stressful events, not simply mediated by sympathetic nervous tone, might be present in obesity.

Eating behavior affects quality of life in type 2 diabetes mellitus

We evaluated the prevalence of disordered eating behavior in 168 unselected outpatients with type 2 diabetes mellitus (T2DM) and the effects on the health related quality of life (HRQL). Subjects in generally good glycemic control, treated by diet or oral hypoglycemic agents (58% M; 63.8±SD 10.1 years; BMI, 29.7±5.9 kg/m2) completed self-administered questionnaires for HRQL (SF-36) and eating behavior [(Three-Factor Eating Questionnaire (TFEQ); Binge Eating Scale (BES)]. Data on HRQL were computed as effectsizes in comparison to population norm. The prevalence of altered TFEQ scales was not different between genders, and varied between 22.1% (disinhibition) and 41.4% (restriction), but only 6.7% had a positive BES score. Age (OR, 0.58 for decade; 95% CI, 0.39–0.87), duration of diabetes (OR, 1.33 for 5 years; 1.01–1.74) and BMI (OR, 1.11; 1.04–1.18) were predictive for the presence of disinhibition. BMI also predicted hunger (OR, 1.16; 1.08-1.25). SF36 domains were not different in relation to positive BES. Disinhibition at TFEQ was significantly associated with poor social functioning (p=0.018) and role-emotional (p=0.022), whereas hunger was associated with poor physical functioning (p=0.010), role-physical (p=0.0014), social functioning (p=0.015) and role-emotional (p=0.0001). Metabolic control, duration of diabetes, and the presence of complications were not associated with HRQL. A disordered eating behavior may be present in T2DM patients, and is associated with poor HRQL. This condition must be considered for an olistic approach to weight control.

Effects of Physical Exercise on the Quality of Life of Individuals with Diabetes and Obesity

Health-related quality of life (HRQL) corresponds to a multidimensional concept, summarized as the satisfaction of the individuals with their life, specifically related to the individual’s perception of his/her health status (somatic as well as mental) and the limitations to functioning related to health, independent of socioeconomic conditions. All aspects are considered as reported by patients. In metabolic diseases, as any chronic condition, HRQL has become a relevant target of interventions, and there is evidence that in diabetes and obesity the participation in programs of physical activity is significantly associated with better health status and HRQL, not limited to physical domains, but extending to mental health. All actors of the therapeutic process need to reconsider the importance of physical activity. It is a very demanding challenge for the coming years.

Effects of long-term oral misoprostol administration on hepatic amino acid–nitrogen metabolism in patients with cirrhosis

BACKGROUND The acute infusion of a Prostaglandin of E series 1 (PGE1) analogue results in nitrogen sparing in cirrhosis. AIMS To test the effects of long-term oral PGE1 on hepatic and whole-body nitrogen metabolism. PATIENTS AND METHODS Ten patients with advanced cirrhosis were studied in paired experiments, before and 30-50 days after oral misoprostol therapy. alpha-Amino-nitrogen levels and urea-nitrogen synthesis rate were measured in the post-absorptive state and in response to continuous alanine infusion (2 mmol/kg per hour for 4.5h). Data were used to compute the functional hepatic nitrogen clearance, i.e. the slope of the regression of alpha-amino-N levels to urea-N synthesis rate, and the apparent nitrogen exchange. RESULTS Misoprostol reduced urea-N synthesis rate (during fasting and in response to alanine), resulting in a positive nitrogen exchange. The functional hepatic nitrogen clearance slightly increased, and the regression line was rightwards shifted, indicating a reduced urea synthesis rate at any alpha-amino-N concentration. Amino acid- and ammonia-N did not accumulate in plasma. No systematic effects on insulin and glucagon were observed. CONCLUSIONS Data are consistent with a nitrogen sparing mechanism of misoprostol, not mediated by hormone levels. These effects may be beneficial in clinical hepatology, and need to be tested in controlled trials.