Stefania Natale

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.

WHO and ADA criteria for the diagnosis of diabetes mellitus in relation to body mass index. Insulin sensitivity and secretion in resulting subcategories of glucose tolerance.

OBJECTIVE: To determine the influence of body mass index (BMI) on agreement between the American Diabetes Association (ADA) and the new World Health Organization diagnostic criteria for the diagnosis of diabetes mellitus and to investigate the metabolic profile of the resulting subcategories.DESIGN: Cross-sectional studySUBJECTS: A total of 3018 subjects with no previous history of diabetes and fasting glucose <7.8 mmol/l, with a wide range of BMIs.MEASUREMENTS: (1) Prevalence of impaired glucose regulation (IGR) and diabetes (DM) according to ADA and WHO diagnostic criteria; (2) basal and post-load insulin sensitivity and secretion, calculated on the basis of data derived from an oral glucose tolerance test (OGTT).RESULTS: The diagnosis according to the two classifications was concordant in 2490 subjects, discordant in 528 (452 were identified as impaired glucose tolerance (IGT) and 76 as DM only by means of OGTT). The disagreement increased with increasing BMI, being as high as 25.3% in subjects with BMI ≥35 kg/m2. Subjects with isolated fasting hyperglycaemia were mainly characterised by reduced insulin sensitivity and secretion in the basal state, but normal first-phase insulin secretion and moderately reduced insulin sensitivity after glucose challenge. Subjects with isolated 2 h hyperglycaemia were mainly characterised by normal basal insulin secretion and by a marked insulin resistance associated with a blunted first-phase insulin secretion after the glucose load.CONCLUSIONS: The disagreement between ADA and WHO classifications is particularly relevant in obesity, making OGTT mandatory in these subjects. Different pathogenic mechanisms are involved in isolated fasting or post-load hyperglycaemia, possibly related to a different site of insulin resistance (hepatic vs peripheral), and/or to a different disregulation of insulin secretion (basal vs post-load). A correct identification of the underlying mechanism(s) is the rationale for future studies to detect the effectiveness of different pharmacological or behavioural approaches.

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.